The search for new antimicrobials should take into account drug resistance phenomenon. Medicinal plants are known as sources of potent antimicrobial compounds including flavonoids. The objective of this invest...
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Σάββατο 15 Σεπτεμβρίου 2018
Antimicrobial activities of flavonoid glycosides from Graptophyllum grandulosum and their mechanism of antibacterial action
Mutational and copy number asset of primary sporadic neuroendocrine tumors of the small intestine
Abstract
Small intestine neuroendocrine tumors (SI-NETs) represent the most common histotype among small intestine neoplasms, and metastatic disease is usually present at diagnosis. A retrospective series of 52 sporadic primary surgically resected SI-NETs, which were metastatic at diagnosis, was analyzed by high-coverage target sequencing (HCTS) for the mutational status of 57 genes and copy number status of 40 genes selected from recently published genome sequencing data. Seven genes were found to be recurrently mutated: CDKN1B (9.6%), APC and CDKN2C (each 7.7%), BRAF, KRAS, PIK3CA, and TP53 (each 3.8%). Copy number analysis showed frequent allelic loss of 4 genes located on chromosome 18 (BCL2, CDH19, DCC, and SMAD4) in 23/52 (44.2%) and losses on chromosomes 11 (38%) and 16 (15%). Other recurrent copy number variations were gains for genes located on chromosomes 4 (31%), 5 (27%), 14 (36%), and 20 (20%). Univariate survival analysis showed that SRC gene copy number gains were associated with a poorer prognosis (p = 0.047). Recurrent copy number variations are important events in SI-NET and SRC may represent a novel prognostic biomarker for this tumor type.
https://ift.tt/2xcIwYu
Multicriteria Decision Model and Thermal Pretreatment of Hotel Food Waste for Robust Output to Biogas: Case Study from City of Jaipur, India
The anaerobic batch test (45 days at 37°C) was performed to describe the effect of thermal pretreatment at moderate temperatures (60, 80, and 100°C) over durations of 10 and 20 minutes on the enhancement of biogas production using hotel food waste from city of Jaipur, India. The results showed that the total cumulative biogas production with thermal pretreatment (100°C, 10 minutes) was 41% higher than the control. Also, this alternative gets first rank using multicriteria decision making model, VIKOR. This outcome was obtained due to the enhancement of degradation of organic compounds such as protein and volatile solids that occurred in the linear trend. Modified Gompertz and Logistic models were used to study the effect of different pretreatment parameters on lag time and biogas yield. Scanning electron microscopy and Fourier transform infrared spectroscopy were also employed to investigate the effect of thermal pretreatment on the physiochemical properties of food waste.
https://ift.tt/2MzDOZV
A cross-sectional study of the relationship between sexual compulsivity and unprotected anal intercourse among men who have sex with men in shanghai, China
HIV prevalence among men who have sex with men (MSM) in China is rising rapidly, and unprotected anal intercourse (UAI) is associated with HIV transmission. Recent research has shown that associations between ...
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Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model
Helicobacter pylori is a major aetiologic agent associated with gastritis. H. pylori infections increase the expression of the Toll-like receptor (TLR), which in turn modulates the expression of microRNA (miRNA)-...
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Phenotypic and functional heterogeneity of peripheral γδ T cells in pulmonary TB and HIV patients in Addis Ababa, Ethiopia
Previous studies reported HIV infection alters the distribution and function of γδ T cells and their subsets. γδ T phenotypes in healthy and diseased individuals has received little attention in Ethiopia. We c...
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MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B
Journal Name: Biological Chemistry
Issue: Ahead of print
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The impact of radiation therapy on lymphocyte count and survival in metastatic cancer patients receiving PD-1 immune checkpoint inhibitors
The impact of radiation therapy on circulating lymphocyte count and survival in metastatic cancer patients receiving immune checkpoint inhibitors (ICI) is unknown. In this retrospective review of 110 patients with metastatic NSCLC, melanoma, or RCC who received RT and PD-1 inhibitors, patients treated with >5 fractions of extracranial RT were more likely to experience severe lymphopenia (<500 cells/mL). Severe lymphopenia at the time of ICI initiation was independently associated with survival.
https://ift.tt/2NgGHnI
Impaired performance of patients with writer’s cramp in complex fine motor tasks
WC is described as a task-specific dystonia and characterized by involuntary contractions of muscles of the hand and arm triggered by writing (Albanese et al., 2013).
https://ift.tt/2D2A17R
The study of exercise tests in paroxysmal kinesigenic dyskinesia
Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of the paroxysmal movement disorders, which is characterized by transient and recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements (Bruno, et al., 2004, Gardiner, et al., 2015). The knowledge of PKD has been accumulating recently; however, the underlying mechanisms remain mysterious. One hypothesis about PKD is that it could be a central nervous system ionic channelpathy (Bhatia, et al., 2000, Celesia 2001, Chen, et al., 2011), since the attacks are often responsive effectively to the ion channel blockers (Huang, et al., 2015).
https://ift.tt/2CY5XdK
Reply to “Which small sharp spikes are benign epileptiform transients of sleep?”
We thank Wennberg et al. for their comment (Wennberg et al., 2018) on our recent paper showing that a subset of hippocampal epileptiform discharges are associated with small sharp spikes (SSS) on scalp EEG (Issa et al., 2018). In their letter, Wennberg et al. raise and begin to address the important clinical question of which SSS are benign and which are not.
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Which small sharp spikes are benign epileptiform transients of sleep?
There is no doubt that some spikes in patients with mesial temporal lobe epilepsy can appear on scalp EEG to resemble benign epileptiform transients of sleep (BETS), a.k.a. small sharp spikes, as nicely demonstrated in the recent paper by (Issa et al., 2018).
https://ift.tt/2NdshVk
Secondary hypokalemic periodic paralysis as a rare clinical presentation of Conn syndrome
Hypokalemic periodic paralysis (hypoPP) is characterized by episodes of sudden-onset muscle weakness associated with low plasma potassium (<3,5 mmol/l). Since the generalized or focal muscle weakness in hypoPP lasts from a few minutes to several days, diagnostic delay is common and affected patients often receive a diagnosis of functional disorder. Primary hypoPP are a group of hereditary skeletal muscle channelopathies, usually with infantile or juvenile onset of symptoms, that are caused by mutations in CACNA1S or SCN4A genes (Statland and Barohn, 2013) eventually determining an altered muscle excitability and electromechanical coupling.
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Minute duodenal metastasis in a patient with thoracic esophageal squamous cell carcinoma successfully treated with chemoradiotherapy
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2NhrEKc
Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
micro-RNAs (miRNAs) are short and highly homologous RNA sequences, serving as post-transcriptional regulators of messenger RNAs (mRNAs). Current miRNA detection methods vary in sensitivity and specificity. We describe a protocol that combines in situ hybridization and immunostaining for concurrent detection of miRNA and protein molecules on mouse heart tissue sections.
https://ift.tt/2NOGg3e
Approach to record linkage of primary care data from Clinical Practice Research Datalink to other health-related patient data: overview and implications
Abstract
Record linkage is increasingly used to expand the information available for public health research. An understanding of record linkage methods and the relevant strengths and limitations is important for robust analysis and interpretation of linked data. Here, we describe the approach used by Clinical Practice Research Datalink (CPRD) to link primary care data to other patient level datasets, and the potential implications of this approach for CPRD data analysis. General practice electronic health record software providers separately submit de-identified data to CPRD and patient identifiers to NHS Digital, excluding patients who have opted-out from contributing data. Data custodians for external datasets also send patient identifiers to NHS Digital. NHS Digital uses identifiers to link the datasets using an 8-stage deterministic methodology. CPRD subsequently receives a de-identified linked cohort file and provides researchers with anonymised linked data and metadata detailing the linkage process. This methodology has been used to generate routine primary care linked datasets, including data from Hospital Episode Statistics, Office for National Statistics and National Cancer Registration and Analysis Service. 10.6 million (M) patients from 411 English general practices were included in record linkage in June 2018. 9.1M (86%) patients were of research quality, of which 8.0M (88%) had a valid NHS number and were eligible for linkage in the CPRD standard linked dataset release. Linking CPRD data to other sources improves the range and validity of research studies. This manuscript, together with metadata generated on match strength and linkage eligibility, can be used to inform study design and explore potential linkage-related selection and misclassification biases.
https://ift.tt/2QxEnqc
Light-sheet Fluorescence Microscopy for the Study of the Murine Heart
https://ift.tt/2xnla1A
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
https://ift.tt/2NOvTwk
Long-term survival and five year hospital resource usage following traumatic brain injury in Scotland from 1997-2015: a population-based retrospective cohort study
Publication date: Available online 14 September 2018
Source: Injury
Author(s): James J.M. Loan, Neil W. Scott, Jan O. Jansen
ABSTRACT
Background
It is unclear if traumatic brain injury (TBI) results in excess mortality compared with head injury without injury to neural structures (HI). Because TBI populations exhibit significant demographic differences from uninjured populations, to determine the effect of TBI on survival, it is essential that a similarly injured control population be used. We aimed to determine if survival and hospital resource usage differ following TBI compared with HI.
Methods
This retrospective population-based cohort study included all 25 319 patients admitted to a Scottish NHS hospital from 1997-2015 with TBI. Participants were identified using previously validated ICD-10 based definitions. For comparison, a control group of all 194 049 HI cases was also identified. Our main outcome measures were hazards of all-cause mortality for patients with TBI, compared with those with HI, over the 18-year follow-up period; and odds of mortality at one month post-injury. Number of days spent as inpatients and number of outpatient attendances per surviving month post-injury were used as measures of resource utilisation.
Results
The adjusted odds ratio for mortality in the first month post-injury for TBI, compared with HI, was 7.12 (95% confidence interval [CI] 6.73-7.52; p < 0.001). For the remaining 18-year study period, the hazards of morality after TBI were 0.93 (CI 0.90-0.96; p < 0.001). During the five-year post-injury period, brain injury was associated with 2.15 (CI 2.10-2.20; p < 0.001) more days spent as inpatient and 1.09 times more outpatient attendances (CI 1.07-1.11; p < 0.001) compared with HI.
Conclusions
Although initial mortality following TBI is high, survivors of the first month post-injury can achieve comparable long-term survival to HI. However, this is associated with, and may require, increased utilisation of hospital services in the TBI group.
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The impact of enoxaparin administration in relationship to hemorrhage in mild traumatic brain injury
Publication date: Available online 14 September 2018
Source: Injury
Author(s): Teena Dhir, Eric Weiss, Katarzyna Wolanin, Simran Randhawa, Solomon Samuel, Corrado Minimo, Griffin Becker, Brian McGreen, Chase Kriza, Niki Patel, Mark Kaplan, Pak Leung
Abstract
Background
: Venous thromboembolism prophylaxis in the general trauma population is well established. However, risk of increased intracranial hemorrhage in traumatic brain injury (TBI) population is of concern. The aim for this study is to identify a reproducible model of mild traumatic brain injury (mTBI), evaluated by clinical and histological markers and test the hypothesis that enoxaparin increases the risk of spontaneous brain hemorrhage.
Methods
: 40 male Sprague Dawley rats were randomly assigned to 5 groups: group 1 (sham) with no TBI along with 4 groups comparing mTBI with and without pharmacological intervention using enoxaparin at 24 hours and 72 hours respectively. Mild traumatic brain injury was induced using a weight drop apparatus, with a clinical endpoint of time to right (TTR), along with histological and spectrophotometer analysis for qualitative hemorrhage.
Results
: There is a statistically significant difference between group 1 (sham) and all other groups with a mean longer time to right of 64 seconds (p = 0.005) in the mTBI groups. There was a statistically significant difference between group 1 (sham) and all other groups with an increase of 6 g/dL hemoglobin (p < 0.001) in the mTBI groups with no difference in hemorrhage between groups that were treated with enoxaparin.
Conclusion
: The weight drop apparatus is a reproducible model for mTBI that has correlations with clinical and qualitative data. This model was able to produce clinical signs of concussion, as reflected by longer TTR and increased hemoglobin in the mTBI groups. Upon further analysis, there wasno increase in hemorrhage in the pharmacological intervention groups with enoxaparin.
https://ift.tt/2NdyaBL
Trauma Assessment and Follow up with Integration of modern Communication devices (TRAFIC). A pilot study
Publication date: Available online 14 September 2018
Source: Injury
Author(s): Tosan Okoro, Ann-Marie Hutchison, Jennifer Wong, Musab Al-Musabi, Victoria Gibbs, Ian Pallister
Abstract
Objectives
This pilot study aimed to evaluate the feasibility of prospectively collecting electronic PROMs on patients being assessed as a result of musculoskeletal trauma, using a web-based application (APP), administered onto tablet and desktop computers (TCs or DCs) in the outpatient setting.
Methods
Following local research ethics approval, a web-based APP (TRAFIC) was developed. It consisted of a total of 12 questions (demographic information, employment, and rehabilitation status as well as quality of life (EQ5D)). The APP was viewable on TCs, with DCs being used in review cubicles when necessary with assistance from a medical professional. Eligible patients were invited to use TRAFIC during the 'Lag period'; the time period from the patient 'booking in' to 'being called' for their appointment. An evaluation of the total time spent using the app (APP-time), was recorded as well as the total time spent in the outpatient department (CLINIC-time) for all patients recruited. CLINIC-time was also assessed for a control group of patients not utilising the APP during their outpatient assessment.
Results
One hundred patients were recruited for the study n = 50 males, n = 50 females with a mean age of 49.1 (± 17.6 years). All recruited patients completed the questionnaire items with a median APP-time of 5 minutes (range 2-118 min). The median 'Lag period' was 16 minutes. (Range 2-166 min), with a median CLINIC-time of 81 minutes (range 4–428). The CLINIC-time was higher than for the control group (median 67 minutes (range 18-242) but this was not statistically significant (Mann Whitney U test; p = 0.199).
Conclusions
Electronic PROMs collection in the musculoskeletal trauma outpatient clinic using a web-based APP is feasible, with the APP-time falling well within the 'Lag period', and no significant impact on the total time spent for the appointment.
https://ift.tt/2D08vIg
TUSC2P suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and correlates with disease prognosis
Abstract
Background
Pseudogenes are RNA transcripts with high homology with its parent protein-coding genes. Although pseudogenes lost the ability to produce protein, it still exert import biological function, and play important role in the pathogenesis of a wide varity of tumors; However, the role of pseudogenes in esophageal squamous cell carcinoma (ESCC) is poorly understood.
Methods
TUSC2P function in ESCC were explored using both in vitro and in vivo experiments cell proliferation, invasion and apoptosis assay was performed to evaluated the effect of TUSC2P on the tumor biology of ESCC. Expression of relative genes was assessed by quantitative real-time PCR (qRT-PCR) and western blotting in EC109 and TE-1 cell, as well as ESCC patients. 3'UTR luciferase assay was used to confirm the direct binding of miRNAs with TUSC2 and TUSC2P 3'UTR. Relation betweenTUSC2P, TUSC2 and ESCC prognosis was predicted by survival analysis (n = 56).
Results
Pseudogene TUSC2P was down regulated in ESCC tissues compared with paired normal adjacent tissues, and the expression of TUSC2P was significantly correlated with survivalof ESCC patients. Over expression of TUSC2P in EC109 and TE-1 cells resulted in altered expression of TUSC2, thus inhibited proliferation, invasion and promoted apoptosis. Dual luciferase assay demonstrated that TUSC2P 3'UTR decoyed miR-17-5p, miR-520a-3p, miR-608, miR-661 from binding to TUSC2.
Conclusions
TUSC2P can suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and may also serve as a prognostic factor for ESCC patients.
https://ift.tt/2xcWABz
Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation
Abstract
Background
An emerging immunotherapy is infusion of tumor infiltrating Lymphocytes (TIL), with objective response rates of around 50% versus 19% for ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly personalized and complex therapy. It requests substantial upfront investments from the hospital in: expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics. Therefore, an early health economic modelling study, as part of a Coverage with Evidence Development (CED) program, was performed.
Methods
We used a Markov decision model to estimate the expected costs and outcomes (quality-adjusted life years; QALYs) for TIL versus ipilimumab for second line treatment in metastatic melanoma patients from a Dutch health care perspective over a life long time horizon. Three mutually exclusive health states (stable disease (responders)), progressive disease and death) were modelled. To inform further research prioritization, Value of Information (VOI) analysis was performed.
Results
TIL is expected to generate more QALYs compared to ipilimumab (0.45 versus 0.38 respectively) at lower incremental cost (presently €81,140 versus €94,705 respectively) resulting in a dominant ICER (less costly and more effective). Based on current information TIL is dominating ipilimumab and has a probability of 86% for being cost effective at a cost/QALY threshold of €80,000. The Expected Value of Perfect Information (EVPI) amounted to €3 M.
Conclusions
TIL is expected to have the highest probability of being cost-effective in second line treatment for advanced melanoma compared to ipilimumab. To reduce decision uncertainty, a clinical trial investigating e.g. costs and survival seems most valuable. This is currently being undertaken as part of a CED program in the Netherlands Cancer Institute, Amsterdam, the Netherlands, in collaboration with Denmark.
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LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling
Abstract
Background
In this research, we aimed to investigate the biological functions of LIM domain only 3 (LMO3) in hepatocellular carcinoma (HCC) and uncover the underlying molecular mechanism in it.
Methods
HCC tissue microarray (n = 180) was used to analyze the correlation between LMO3 expression and clinicopathological findings. In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions. In vivo intrahepatic and lung metastasis models were used to determine the role of LMO3 in HCC metastasis. Quantitative real-time PCR, western blotting and immunohistochemical staining were performed to investigate the expression and mechanism of LMO3 in HCC.
Results
We found that the expression of LMO3 was significantly upregulated in HCC tissues, and it was closely related to clinicopathological findings and patient prognoses. Knockdown of LMO3 suppressed the invasion and anoikis inhibition of HCC cells in vitro. Meanwhile, the metastasis of SMMC-7721 cells was also suppressed by LMO3 knockdown in vivo. Furthermore, we found that LMO3 knockdown increased the phosphorylation of YAP and LATS1, and decrease Rho GTPases activities. LMO3 directly interacted with LATS1, and thus suppressed Hippo signaling. Recombinant LMO3 (rLMO3) protein administration decreased the phosphorylation of YAP and LATS1, and increased Rho GTPases activities. The inhibitors of the Hippo pathway abrogated rLMO3 protein-induced HCC cell invasion and anoikis inhibition.
Conclusions
These results suggest that LMO3 promotes HCC cell invasion and anoikis inhibition by interacting with LATS1 and suppressing Hippo signaling. LMO3 may serve as a potential therapeutic target for HCC in future.
https://ift.tt/2QvG2g5
EM Nerd-The Case of the Anatomic Heart Revisited
If Maslow were to generate a hierarchy of needs to assess the utility of the coronary CT angiogram (CCTA) in the Emergency Department for the evaluation of chest pain it would look something like this: We have fairly robust data demonstrating the use of CCTA does not improve mortality, nor does it decrease the rate […]
EMCrit Project by Rory Spiegel.
https://ift.tt/2D80MYO
Unilateral cataract associated with eyelid ash-leaf macule in tuberous sclerosis complex
A 9-month-old male child with tuberous sclerosis complex presented with ash-leaf macules on the left periocular region and ipsilateral dense cataract. Fundus showed retinal astrocytic hamartomas. This case is reported for unilaterality of congenital cataract on the same side of eyelid ash-leaf macule in tuberous sclerosis.
https://ift.tt/2xntrD4
Periocular contact dermatitis with use of topical voriconazole 1% in mycotic keratitis
We present two cases of culture-proven fungal keratitis on natamycin treatment which developed periocular erythema, oedema, burning sensation and pruritus within 48 hours of the addition of topical voriconazole. On clinical examination, periocular erythema with induration was noted. A diagnosis of orbital cellulitis was suspected, but the absence of pain and tenderness refuted the diagnosis on clinical grounds. A dermatology consultation was sought, and a diagnosis of periocular contact dermatitis with voriconazole was made. A skin patch test was performed with the same medication; however, it was negative. Topical voriconazole therapy was withdrawn, and the patient was prescribed cold compresses and oral antihistamine medication, to which they responded well.
https://ift.tt/2xlIjS3
Chemotherapy in combination with stereotactic body radiation therapy (SBRT) for oligometastatic pancreatic cancer
Metastatic pancreatic cancer is characterised by poor prognosis. High toxicity of chemotherapy limits its use in elderly patients with severe comorbidities. Meanwhile, in metastatic disease, local treatment did not show the positive effect on life expectancy. We present a clinical case of a 72-year-old woman with metastatic pancreatic adenocarcinoma tumour, node, metastases (T3N0M1) (according to the seventh TNM classification of the International Union Against Cancer). Chemotherapy led to partial response, but later was stopped due to severe toxicity. Thereafter, consolidating radiosurgical treatment was performed. Dose to pancreatic and liver lesions was 35 Gy in five fractions. After 9 months, only one liver lesion and primary pancreatic tumour, stable in size were determined by MRI. At present time, the patient is alive and in good condition, the disease is stable 50 months after stereotactic body radiation therapy (SBRT). SBRT provides a high level of local control and in combination with systemic treatment can potentially increase survival.
https://ift.tt/2xjJ3qV
Continent cutaneous diversion pouch calculi
Description
A 62-year-old female patient who presented at our centre with dull aching right flank pain of 6 months duration. She had a history of radical cystectomy and cutaneous continent urinary diversion (Indiana pouch) done 20 years ago for muscle invasive urothelial carcinoma of urinary bladder. The patient followed up regularly since operation. However, for last 3 years, the patient was lost to follow-up. On further eliciting the history, she mentioned her inability to perform pouch irrigation and clean intermittent catheterisation regularly during this period.
On examination, a lump was palpable in the right lumbar region in the region of continent pouch. It was firm in consistency around 5x5 cm in size and did not move with respiration. There was no pain/tenderness on palpation. The stoma was healthy, flush to skin, functioning and easily catheterisable.
Her complete haemogram including renal function test and liver function test were normal. A plain abdominal X-ray revealed multiple...
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Rare case of meningococcal sepsis-induced testicular failure, primary hypothyroidism and hypoadrenalism: Is there a link?
Severe illness can lead to multiple transient endocrinopathies. In adult patients, neuroendocrine alterations include sick euthyroid syndrome, an increase in corticosteroid levels, increase in prolactin levels, decreased insulin growth factor 1 levels and hypogonadism. We report the case of a 24-year-old man with meningococcal sepsis with multiple end-organ complications who developed persistent non-autoimmune hypothyroidism, adrenal insufficiency and primary hypogonadism all requiring hormone replacement. While adrenal insufficiency as part of the Waterhouse-Friderichsen syndrome is well described, reports of primary hypothyroidism and persistent primary hypogonadism in severe illness are exceedingly rare. Multiple combined endocrinopathies as in this case have not been reported previously. This case highlights the necessity of screening for endocrine abnormalities in severe illness and the need for treatment if persistent. It also raises a novel concept of meningococcal sepsis causing multiple endocrinopathies possibly via disseminated intravascular coagulopathy-related ischaemic damage.
https://ift.tt/2xnyQtw
Recurrent pleural effusion in a young woman: calcifying fibrous tumour of the pleura
We present the case of a 23-year-old woman with a long-standing history of recurrent left-sided pleural effusion unrelated to her menstrual cycle. At her last presentation, non-contrast-enhanced chest CT showed a pleural effusion and a lower left hemithorax mass, both large enough to cause complete collapse of the lower lobe and partial collapse of the upper lobe. Thoracoscopic surgery revealed a multilobulated mass originating from the dome of the diaphragm with pleural deposits. Histopathology diagnosed this as a calcifying fibrous tumour of the pleura, a rare benign tumour with excellent prognosis when completely excised.
https://ift.tt/2xbaVys
Natural killer/T-cell lymphoma and secondary haemophagocytic lymphohistiocytosis in pregnancy
Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disorder. It is challenging to diagnose due to its rarity and variation in clinical presentation, laboratory abnormalities and underlying aetiologies. A reproductive-aged woman, gravida 2 para 1001 at 27 weeks gestation presented with fever, hypotension and subacute upper respiratory infection. She delivered a male infant by caesarean section secondary to fetal distress. Subsequently, she was diagnosed with T-cell lymphoma and secondary HLH. Despite management with supportive care and multiple chemotherapeutic agents, she ultimately died of multiorgan failure. Patients with HLH secondary to malignancy have a particularly poor prognosis. This case highlights the importance of considering secondary HLH in the differential diagnosis of a patient with fever, pancytopenia and systemic symptoms of unclear aetiology in pregnancy.
https://ift.tt/2xidFcz
Primary intracranial leiomyosarcoma among patients with AIDS in the era of new chemotherapeutic and biological agents
Primary intracranial leiomyosarcoma (PIL) is a rare non-infectious aetiology of focal mass lesions among HIV-infected individuals. With only 16 published cases worldwide, information on its pathophysiology, risk factors, clinical course and management options is limited. We report two cases of PIL in HIV-infected Filipino men who presented with 1–3 months history of persistent headache, progressing in severity. Both had cranial MRI revealing intracranial mass diagnosed as leiomyosarcoma by excision biopsy and immunohistochemical staining. Both patients underwent adjuvant cranial radiotherapy and chemotherapy. Biologics were initiated in one patient. Both patients were alive with evidence of the disease.
https://ift.tt/2xcOEQN
Urachal adenocarcinoma
Description
A 40-year-old male patient presented at the outpatient department with ulcerative swelling with foul smelling discharge from lower half of abdomen for last 3 months. He had a history of haematuria with increased frequency of micturition for last 6 months accompanied by loss of appetite and subsequent weight loss. There was no history of nocturia, urgency or incontinence.
On physical examination, he was found to have an ulceroproliferative growth around 5x3 cm size in the infraumbilical region with urinary discharge near one end as shown in figure 1.
Figure 1
Ulceroproliferative growth in the infraumbilical region arising from urinary bladder.
It was small to begin with and progressively increased in size to reach the present state.
The growth demonstrated an unhealthy ulcer with everted margins and areas of slough. It was friable and bled actively on manipulation. Rest of the abdominal...
https://ift.tt/2x8DCvR
Common iliac artery thrombosis as a possible complication of the pluck technique in nephroureterectomy
Common iliac artery (CIA) thrombosis is a rare surgical complication which may cause serious leg damage and may occasionally be fatal. We experienced two cases of CIA thrombosis in nephroureterectomy with the pluck technique for upper tract urothelial carcinoma. Patients were treated using emergent femoro–femoral bypass, and one patient was treated with fasciotomy of the lower extremity for compartment syndrome. CIA thrombosis is considered a possible complication of nephroureterectomy, particularly with the pluck technique in open surgery. Arterial thrombosis in intrapelvic surgery including nephroureterectomy should be carefully considered for patients at risk.
https://ift.tt/2xlIwoj
Unusual presentation of pancreatitis with extrapancreatic manifestations
Pancreatitis, panniculitis and polyarthritis syndrome (PPP syndrome) is a rare and complex manifestation of pancreatitis that is currently reported in few cases. We present this case regarding a 77-year-old man who presented unusually with a 6-week history of bilateral lesions on his lower limbs. During this time, he experienced increasing fatigue, joint pain, and reported fevers and significant weight loss. An incidental serum amylase was found to be significantly elevated and remained elevated throughout his 2-month hospital stay. He never complained of abdominal pain or other typical symptoms of pancreatitis. Histological examination of the leg lesions reported evidence of fat necrosis and changes consistent with pancreatic panniculitis. An abdominal CT scan revealed a well-defined lesion posterior to the neck of the pancreas. Further examination by endoscopic ultrasound revealed chronic inflammatory changes. The patient experienced a long admission and was managed supportively until he was well enough to be discharged home.
https://ift.tt/2xeuGoK
Delayed pressure urticaria due to non-invasive blood pressure monitoring in a previously non-atopic man
Description
A 68-year-old man presented to us with voiding lower urinary tract symptoms due to benign prostatic hyperplasia for which he underwent photovapourisation of prostate using potassium titanyl phosphate laser. The procedure was completed in 104 min uneventfully. Eight hours after the procedure, the patient had burning and itching on his left arm circumferentially in the area where the cuff for non-invasive blood pressure (NIBP) monitoring was applied and on his back. We removed the cuff and in that region of his arm there was erythema along with multiple blisters (figure 1). A similar linear lesion was seen on the right side of his back along the 10th rib (figure 2). We recognised it to be some form of urticaria, and immediately gave the patient an antihistamine (pheniramine). The patient had no history of any skin lesion, neither did he give a history of any allergies. Both lesions...
https://ift.tt/2xeXPjB
Concurrent internal hernia and intussusception after Roux-en-Y gastric bypass
Description
A 32-year-old woman with medical history significant for open Roux-en-Y gastric bypass performed 11 years prior presented to an urgent care with sudden severe epigastric pain associated with nausea and vomiting. She was profoundly hypothermic (91°F) and bradycardic (40 bpm) but maintained normal blood pressure. Laboratory values were grossly within normal limits except for an elevated lactic acid (2.99 mmol/L). Rewarming protocol, broad-spectrum intravenous antibiotics (piperacillin–tazobactam and vancomycin) and intravenous fluid resuscitation were initiated at this time. CT of the abdomen with intravenous and oral contrast demonstrated intussusception at the site of the jejunojejunal anastomosis with severe oedema of the mesentery and focally dilated bowel consistent with a high-grade obstruction due to an internal hernia (figure 1A). The patient was emergently transferred to the hospital and underwent an exploratory laparotomy. Intraoperatively, the intussuscepted segment of small bowel surrounding the jejunojejunal anastomosis was identified with an associated...
https://ift.tt/2xjIi14
Late twiddler syndrome in a patient with a submuscular implantable cardioverter defibrillator
Description
A 20-year-old woman with long-QT syndrome received a submuscular Fortify DR-St Jude implantable cardioverter defibrillator (ICD) after an episode of cardiac arrest. She felt an ICD pocket vibration 23 months later due to a high lead impedance and loss of capture. Chest radiography (figure 1A,B) showed both lead displacement and winding of the leads beside the ICD generator. These findings were confirmed during surgery (figure 1C). The patient strongly denied any box manipulation. She was discharged after new leads implantation with no complications.
Figure 1
(A) and (B) Chest radiography showing both lead displacement and winding of the leads close implantable cardioverter defibrillator generator. (C) Intraoperative finding of lead twisting.
There is a report of three patients with ICD with submuscular devices in whom a twiddler's syndrome occurred despite any risk factors were be seen. It is discussed that the cause...
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Delayed lethal pulmonary air embolism after a gunshot head injury
We present a case of a young male patient with a fatal pulmonary air embolism following a penetrating gunshot head injury. He suffered from severe head trauma including a laceration of the superior sagittal sinus. Operative neurosurgical intervention did not establish a watertight closure of the wounds. Eight days after the trauma, the patient suddenly collapsed and died after an attempt to mobilise him to the vertical. Forensic autopsy indicated pulmonary air embolism as the cause of death. Retrospectively, we postulate an entry of air to the venous system via the incompletely occluded wounds and the lacerated superior sagittal sinus while mobilisation to the vertical created a negative pressure in the dural sinus.
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Polymorphisms in the H19 gene and the risk of lung Cancer among female never smokers in Shenyang, China
Abstract
Background
Long non-coding RNA (lncRNA) H19 is a hot spot in tumor development, progression and metastasis. This study assessed the association between H19 genetic polymorphisms and the susceptibility of lung cancer.
Methods
The case-control study was conducted to evaluate the association between four selected single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052) in H19 gene and the risk of lung cancer. There were 556 female never smoking lung cancer patients and 395 cancer-free controls. Unconditional logistic regression analysis was used to analyze the associations between four SNPs and lung cancer risks by calculating the odds ratios and their 95% confidence intervals. The gene-environment interactions were assessed on both additive and multiplicative scales.
Results
Compared with carriers carrying homozygous CC genotype, there was a statistically significant increased risk of lung cancer for carriers of the rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106–2.313, P = 0.013). In both dominant and recessive models, significant associations were found between rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346 (1.022–1.774) and 1.400 (1.011–1.937), with P values 0.035 and 0.043, respectively. There was no significant correlation between lung cancer risk and rs2735469, rs217727 and rs17658052. Interaction analysis showed that their combined effects had a greater impact on lung cancer than individual effects of polymorphism and cooking smoke exposure. However, further analysis showed that the both additive model and the multiplicative model were not statistically significant.
Conclusion
The polymorphism rs2107425 in H19 gene was associated with the risk of lung cancer among female who never smokes in Shenyang, China.
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Patient Diversity and Population Health-Related Cardiovascular Outcomes Associated with Warfarin Use in Atrial Fibrillation: An Analysis Using Administrative Claims Data
Abstract
Introduction
Anticoagulants are effective for stroke prevention in atrial fibrillation (AF). Data on population health-related cardiovascular outcomes by race/ethnicity and gender are not well described. The aim was to assess the impact of patient diversity on associated cardiovascular outcomes related to warfarin anticoagulation in Medicare beneficiaries with AF.
Methods
Medicare administrative claims data for years 2000–2010 were used to calculate AF prevalence and rates of new AF cases. Three 20% sample cohorts of new AF beneficiaries for years 2000, 2005, and 2007 were extracted and analyzed in a longitudinal study design. The impact of warfarin on associated cardiovascular outcomes was measured with respect to race/ethnicity and gender. Measured outcomes included the risk of stroke, mortality and hospitalization after adjusting for age, gender, race/ethnicity, CHADS2 score and warfarin.
Results
AF prevalence and warfarin use increased while stroke and mortality rates declined across race/ethnicity and gender from 2000 to 2010. Analyses comparing Whites to non-Whites highlighted several disparities: (1) Blacks were 40% (p < 0.0001) more likely to have a stroke even after adjustment for warfarin; (2) in 2007, Hispanics had a 35% (p < 0.01) higher prevalence of stroke and warfarin did not reduce the risk; and (3) Asians had better outcomes. Warfarin reduced stroke less well in women who had a lower risk of death and hospitalization. Despite a > 70% (p < 0.0001) reduction in mortality for warfarin users, Blacks had a 25% (p < 0.0001) higher mortality risk than Whites.
Conclusions
Differences in population health metrics across race/ethnicity and gender exist in AF. Across all metrics, Blacks had comparatively worse outcomes. Patient diversity should be a focus for future investigations in AF to improve outcomes in the whole population.
Funding
National Minority Quality Forum.
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Editorial on Transforming midwifery practice conference
Publication date: Available online 14 September 2018
Source: Women and Birth
Author(s): Linda Sweet, Mark Keough
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Nodding syndrome in Uganda is a tauopathy
Abstract
Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects children in the subsistence-farming communities of East Africa. We report the neuropathologic findings in five fatal cases (13–18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem. There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina. The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed globose neurofibrillary tangles and threads. We conclude that nodding syndrome is a tauopathy and may represent a newly recognized neurodegenerative disease.
https://ift.tt/2xjCkxo
Sex and age interact to determine clinicopathologic differences in Alzheimer’s disease
Abstract
Women reportedly make up two-thirds of Alzheimer's disease (AD) dementia sufferers. Many estimates regarding AD, however, are based on clinical series lacking autopsy confirmation. The Florida Autopsied Multi-Ethnic (FLAME) cohort was queried for AD cases with a total of 1625 identified ranging in age from 53 to 102 years at death. Standard neuropathologic procedures were employed and clinical information was retrospectively collected. Clinicopathologic and genetic data (MAPT and APOE) were stratified by sex. Within the neuropathologically diagnosed AD cohort, the overall number of women and men did not differ. Men were younger at onset of cognitive symptoms, had a shorter disease duration, and more often had atypical (non-amnestic) clinical presentations. The frequency of autopsy-confirmed AD among women and men stratified by age at death revealed an inverse U-shaped curve in men and a U-shaped curve in women, with both curves having inflections at approximately 70 years of age. Regional counts of neurofibrillary tangles differed in women and men, especially when examined by age intervals. Women had overall greater severity of neurofibrillary tangle counts compared to men, especially in the hippocampus. Men were more often classified as hippocampal sparing AD, whereas limbic predominant AD was more common in women. Men and women did not differ in frequency of MAPT haplotype or APOE genotype. Atypical clinical presentations, younger age at onset and shorter disease duration were more frequent in men, suggesting that the lower reported frequency of AD in men may be due to more frequent atypical clinical presentations not recognized as AD. Our data suggest that neuropathologically diagnosed AD cases have the same frequency of women and men, but their clinical presentations and ages at onset tend to differ.
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Cancers, Vol. 10, Pages 333: Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for T4 Squamous Cell Carcinoma of the Maxillary Gingiva
Cancers, Vol. 10, Pages 333: Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for T4 Squamous Cell Carcinoma of the Maxillary Gingiva
Cancers doi: 10.3390/cancers10090333
Authors: Hiromasa Endo Kanako Takayama Kenji Mitsudo Tatsuya Nakamura Ichiro Seto Hisashi Yamaguchi Takashi Ono Motohisa Suzuki Yusuke Azami Hitoshi Wada Masao Murakami Iwai Tohnai
This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20–40 mg/m2, 4–6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36–40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70.4–74.8 Gy. The median follow-up was 33 months. The 3-year local control and overall survival rates were 69% and 59%, respectively. Major grade 3 or higher acute toxicities included mucositis, neutropenia, and dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3 or higher late toxicities were observed. These results suggested that proton beam therapy in combination with intra-arterial infusion chemotherapy was not inferior to other treatment protocols and should be considered as a safe and effective option in patients with T4 squamous cell carcinoma of the maxillary gingiva.
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Adolescents’ Endorsement of Communal and Agentic Conflict-Management Strategies with Friends and Romantic Partners
Abstract
To investigate contextual influences on gender differences and similarities, we compared adolescents' endorsement of gender-typed communal/other-focused and agentic/self-focused conflict-management strategies in three relationship contexts: same-gender friends, other-gender friends, and other-gender heterosexual romantic partners. Our 2 Participant Gender (between-subjects) × 3 Relationship Context (within-subjects) mixed factorial design addressed whether findings of prior research (Keener and Strough 2017) with college-aged participants would generalize to adolescents. Participants (n = 103; 47 male adolescents; 56 female adolescents, 14–17 years-old) from the U.S. South Atlantic and Middle Atlantic regions read nine hypothetical conflict scenarios (three per each relationship context) and rated their likelihood of using gender-typed strategies. Young women and men endorsed communal and agentic strategies significantly more in same- and other-gender friendships than in romantic relationships. Across all three relationship contexts, young women reported using significantly more agentic strategies than young men did. In contrast to previous research on college students (Keener and Strough 2017), the predicted Participant Gender x Relationship Context interaction was not significant in the present study. Our findings suggest that developmental processes such as age differences in gender socialization and lack of experience with romantic relationships might explain why findings from college students did not generalize to adolescents.
https://ift.tt/2xmeqB4
Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis
Abstract
The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 μmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-α, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.
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Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a 13 C NMR metabolomic study
Abstract
Alzheimer's disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using 13C NMR metabolomics in combination with intravenous [1-13C]-glucose infusion in APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found that brain glucose was significantly accumulated in APP/PS1 mice relative to wild-type (WT) mice. Reductions in 13C fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, γ-aminobutyric acid and aspartate) from [1-13C]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the 13C-enrichments of the C3 of alanine were significantly lower and the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than WT mice. Taken together, the development of amyloid pathology could cause a reduction in glucose utilization and further result in decreases in energy and neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.
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Early liver transplantation in neonatal-onset and moderate urea cycle disorders may lead to normal neurodevelopment
Abstract
Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to hyperammonemia. Neurodevelopmental outcomes of patients with UCDs depend on the maximum ammonia concentration (MAC) in the blood during onset. MAC ≥360 μM is a marker of poor neurodevelopmental outcomes. We investigated the neurodevelopmental outcomes and MAC at onset for 177 patients with UCDs in Japan (median age, 8 years and 2 months; range, 10 days–72 years), including 57 patients with male ornithine transcarbamylase (OTCD), 59 patients with female OTCD, 23 patients with carbamoyl-phosphate synthetase 1 deficiency (CPSD), 28 patients with arginosuccinate synthetase deficiency, 9 patients with arginosuccinate lyase deficiency (ALD), and 1 patient with arginase 1 deficiency. Neurodevelopmental outcomes of patients with CPSD and ALD were poor because most had neonatal onset with blood MAC ≥300 μM at onset. Although OTCD, particularly female late-onset OTCD, has good neurodevelopmental outcomes among those with UCDs, it is not necessarily a mild disease with good long-term outcomes. Patients with severe UCDs and MAC ≥300 μM at onset should undergo liver transplantation (LT). Moreover, this study suggested that if the onset of UCD began during the neonatal period, then even UCD patients with MAC <300 μM at onset should undergo LT to protect the brain.
https://ift.tt/2QyGIBt
Incidence of diarrhea and associated risk factors in patients with traumatic brain injury and enteral nutrition
Abstract
To determine the occurrence of diarrhea and associated factors in critically ill patients with traumatic brain injury (TBI) in use of nutritional therapy. Prospective cohort study conducted in an Intensive Care Unit (ICU) of a General Hospital reference in trauma. We evaluated TBI patients who stayed less than 72 h in the ICU, who were using EN for at least 48 h. Definition of diarrhea it was considered three or more episodes of liquid stools or semi-liquid at 24 h. For analysis were evaluated demographic, epidemiological, clinical and nutritional data. Twenty-three patients were evaluated, being 86.9% male, median 33 years old (IQR = 25–52 years) and 16-day ICU stay (IQR = 10–26 days). Diarrhea occurred in 69.6% of the patients and they had a longer time in the ICU (p = 0.007). All patients who used combination prokinetic therapy (metoclopramide and erythromycin) and used antibiotics for more than 8 days had diarrhea (p = 0.057 and p = 0.007, respectively). The incidence of diarrhea was high in TBI patients with enteral nutrition and was associated with the use of antibiotics for more than one week.
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Improving cognitive task in kindled rats by using low frequency stimulation during epileptogenesis
Abstract
Numerous studies indicate that one of the bad effects of epilepsy is cognitive impairment. In this study we focused on the effect of LFS as a potential anticonvulsant agent, during epileptogenesis on cognitive impairments induced by amygdala kindling in rat. Twenty-one adult rats were divided into 3 groups including control (n = 7), kindled (n = 7), and Kindled+LFS (KLFS) (n = 7). Animals in the kindled group received kindling stimulation in a rapid kindling manner (a 3 s train of 50 Hz monophasic pulses of 1 ms duration, 12 times a day) in amygdala whereas control animals had no stimulation. Four packages of LFS (each package consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz) were applied daily after termination of kindling stimulation in KLFS group. Spatial memory of all animals was tested using radial arm maze after termination of stimulation on acquisition trial days and 14 days after the final acquisition trial test. Epileptogenesis process significantly increased working and reference memory error compared to control groups whereas application of LFS immediately after kindling stimulation prevented this impairment in 8 arm radial maze and there was no significant difference between KLS and control groups. Our results indicated that application of LFS during kindling acquisition suppresses memory impairment in epileptogenesis by kindling stimulation.
https://ift.tt/2QycJtk
Metabolic profile of oxidative stress and trace elements in febrile seizures among children
Abstract
Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and young children. The present study aims to assess and compare the serum levels of oxidative stress markers and some essential trace minerals in FS with normal or abnormal EEG and evaluate the effect of antioxidant therapy on the clinical outcome. This study has been carried out on 80 children with FS (40 with simple FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and EEG findings were recorded for the included patients. Biochemical assays of serum nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper (Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in the studied groups. The overall results showed an increased values of NO, MDA and Cu with decreased values of SOD, Zn and Se in patients with FS (simple and complex) in comparison with febrile children without seizures (p < 0.05 for all). Additionally, NO and MDA was increased in complex FS patients with EEG abnormalities in comparison with complex FS with normal EEG findings (p < 0.05); NO and MDA were also significantly decreased after valproate therapy in complex FS patients (p < 0.05 for all). In conclusions, oxidative stress, decreased Zn and Se with increased Cu may play a role in FS. Valproate improves the oxidative stress status in complex FS.
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Gentiopicroside abrogates lipopolysaccharide-induced depressive-like behavior in mice through tryptophan-degrading pathway
Abstract
Targeting neuroinflammatory disturbances has been acknowledged as a potential strategy for treatment of depressive disorder in humans. Over-activation of tryptophan-degrading pathway by pro-inflammatory cytokines resulted in N-methyl-d-aspartate (NMDA)-mediated excitotoxicity, which is implicated in pathophysiology of depression. Gentiopicroside (Gent) has powerful anti-inflammatory property and exhibits promising antidepressant effect in an animal model of pain/depression dyad by down-regulating GluN2B-containing NMDA receptors. Therefore, the present study aimed to investigate the ability of Gent to abolish depressive-like behavior induced by lipopolysaccharide (LPS) in mice. Acute administration of LPS (0.5 mg/kg, i.p.) increased immobility time in both forced swimming test (FST) and tail suspension test (TST) without affecting spontaneous locomotor activity, indicative of depressive-like behavior. Gent (50 mg/kg, i.p.) administered once a day for three consecutive days prevented the development of depressive-like behavior induced by LPS. The antidepressant-like effect was paralleled with restoration of LPS-induced alterations in brain inflammatory mediators (i.e. IL-1β and TNF-α). In addition, Gent prevented over-activation of indoleamine 2,3-double oxygen enzyme (IDO) and recovered GluN2B subunit expression in the PFC challenged by LPS. In conclusion, our results suggested that Gent pretreatment provided protection against LPS-induced depressive-like behavior and the effect appeared to be demonstrated, at least partially, by blocking various steps of tryptophan-degrading pathway.
https://ift.tt/2Qyl4wX
A high-fat diet induced NMRI mouse model of metabolic syndrome: focus on brain-derived neurotrophic factor (BDNF)
Abstract
The association of brain-derived neurotrophic factor (BDNF) as a member of neurotrophin family and metabolic syndrome (MetS) has been proposed, however basic evidence necessary to prove (or disprove) this association in non-genetic animal model is rare. Therefore, we investigated the alteration of encephalic BDNF gene expression in a mouse model of high-fat diet (HFD) induced MetS. To translate MetS, male NMRI mice (9 weeks old; N = 13) fed on a HFD including suet powder (37.50%) and granulated sugar (19.85%) while control mice were fed a diet contained suet powder (6.25%) and granulated sugar (49.09%). We monitored the development of MetS by measuring fasting blood sugar (FBS) and lipid (total cholesterol (TC) and triacylglycerol (TGs)) and lipoprotein (high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C)) profiles, atherogenic index (AI), and somatic indices after 1 and 3 months of dietary interventions. The HFD intake led to increased body weight, liver weight, FBS, TC, and decreased HDL-C as compared to chow diet in mice after first month of dietary intervention. The increased FBS, body weight, abdominal fat mass, TGs, TC, and VLDL-C and decreased HDL-C were observed in HFD-fed mice as compared to those of chow-fed mice at 3th month. The statistical comparison of two HFD groups in two time intervals of 1st and 3th month confirmed that our HFD-induced MetS model was reliable because FBS, TGs and VLDL-C, TC, and AI have been increased significantly during selected time intervals. The AI increased significantly in HFD-fed mice compared to chow-fed mice after 3 months. The AI in HFD-fed mice treated with HFD for 3 months was increased significantly as compared to mice fed HFD for 1 month. Our diet-induced model more closely mimics the changes observed in human MetS and showed that encephalic BDNF gene in mice fed HFD was under-expressed by 0.30 fold with respect to chow-fed mice after 3 months of dietary intervention.
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Antibiotics protect against EAE by increasing regulatory and anti-inflammatory cells
Abstract
A seven day pretreatment course of an oral antibiotic cocktail (Ampicillin, Metronidazole, Neomycin Sulfate, and Vancomycin) was shown to induce changes in peripheral immune regulation and protect mice from signs of experimental autoimmune encephalomyelitis (EAE). To determine if a shorter course of antibiotic pretreatment could also protect the mice from EAE and induce regulatory immune cells, studies were conducted using the same oral antibiotic cocktail for three days. In addition, the CNS was examined to determine the effects of antibiotic pretreatment on EAE disease course and immune modulation within the affected tissue. The shorter three day pretreatment course was also significantly protective against severe EAE in C57BL/6 mice. Moreover, our study found increased frequencies of regulatory cells and a decrease in the frequency of anti-inflammatory macrophages in the spleen of EAE protected mice. Additionally, a chemokine and chemokine receptor array run on mRNA from spinal cords revealed that genes associated with regulatory T cells and macrophage recruitment were strongly upregulated in the antibiotic pretreated mice. Additional RT-PCR data showed genes associated with anti-inflammatory microglia/macrophages were upregulated and pro-inflammatory genes were downregulated. This suggests the macrophages recruited to the spinal cord by chemokines are subsequently polarized toward an anti-inflammatory phenotype. These results lend strong support to the conclusion that a three day course of antibiotic treatment given prior to the induction of severe EAE profoundly protected the mice by inducing regulatory lymphocytes in the periphery and an anti-inflammatory milieu in the affected spinal cord tissue.
https://ift.tt/2QyczlI
Recurrent hepatic failure and status epilepticus: an uncommon presentation of hyperargininemia
Abstract
Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. Herein we report a patient with arginase I (ARG1) deficiency who presented with recurrent nonconvulsive status epilepticus and liver failure. A novel homozygous frameshift mutation c.703_707delGGACTinsAGACTGGACC (p.G235Rfs*20) was detected.
https://ift.tt/2xkolY7
Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway
Abstract
Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg−1,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway.
https://ift.tt/2Qvqhpj
Autozygosity mapping of methylmalonic acidemia associated genes by short tandem repeat markers facilitates the identification of five novel mutations in an Iranian patient cohort
Abstract
Isolated Methylmalonic acidemia/aciduria (MMA) is a group of inborn errors of metabolism disease which is caused by defect in methylmalonyl-CoA mutase (MCM) enzyme. The enzyme has a key function in the catabolism of branched chain amino acids (BCAA, isoleucine, and valine), methionine, and threonine. MCM is encoded by a single gene named "MUT". Other subtypes of MMA are caused by mutations in cblA (encoded by MMAA) and cblB (encoded by MMAB), which is involved in the synthesis of methylmalonyl–coenzyme A cofactor. Different types of mutations have been identified as the cause of MMA. However, the mutation spectrum of MMA in Iran has not been studied so far. Here, we aimed to investigate the MMA causative mutations in the Iranian population. Using STR (Short Tandem Repeat) markers, we performed autozygosity mapping to identify the potential pathogenic variants in 11 patients with clinical diagnosis of MMA. Nineteen STR markers which are linked to the MUT, MMAA and MMAB genes (the genes with known causative mutations in MMA) were selected for PCR-amplification using two recently designed multiplex PCR panels. Next, the families that were diagnosed with homozygous haplotypes for the candidate genes were directly sequenced. Five novel mutations (c.805delG, c.693delC, c.223A > T, c.668A > G and c.976A > G in MUT) were identified beside other 4 recurrent mutations (c.361insT in MUT, c.571C > T and c.197–1 G > T in MMAB and c.1075C > T in MMAA). In silico analyses were also performed to predict the pathogenicity of the identified variants. The mutation c.571C > T in MMAB was the most common mutation in our study.
https://ift.tt/2xje4eB
Modulation of miR-139-5p on chronic morphine-induced, naloxone-precipitated cAMP overshoot in vitro
Abstract
Chronic exposure to morphine can produce tolerance, dependence and addiction, but the underlying neurobiological basis is still incompletely understood. c-Jun, as an important component of the activator protein-1 transcription factor, is supposed to take part in regulating gene expression in AC/cAMP/PKA signaling. MicroRNA (miRNA) has emerged as a critical regulator of neuronal functions. Although a number of miRNAs have been reported to regulate the μ-opioid receptor expression, there has been no report about miRNAs to regulate chronic morphine-induced, naloxone-precipitated cAMP overshoot. Our results showed that chronic morphine pretreatment induced naloxone-precipitated cAMP overshoot in concentration- and time-dependent manners in HEK 293/μ cells. Chronic morphine pretreatment alone elevated both c-Jun protein and miR-139-5p expression levels, while dramatically artificial elevation of miR-139-5p inhibited c-Jun at the translational level. Furthermore, dramatically artificial upregulation of intracellular miR-139-5p limited chronic morphine-induced, naloxone-precipitated cAMP overshoot. These findings suggested that miR-139-5p was involved in regulating chronic morphine-induced, naloxone-precipitated cAMP overshoot in a negative feedback manner through its target c-Jun, which extends our understanding of neurobiological mechanisms underlying morphine dependence and addiction.
https://ift.tt/2Qz0Ymy
Association between abnormal thalamic metabolites and sleep disturbance in patients with end-stage renal disease
Abstract
Sleep disturbances are common in end-stage renal disease (ESRD) patients. However, the underlying neuropathological mechanisms are largely unclear. Previous studies have revealed the important role of the thalamus in the potential mechanisms of sleep disorders. We hypothesized that the sleep disturbances in ESRD patients may correspond to metabolic changes of thalamus and the uremic factors may have a vital contribution on these changes. We performed multi-voxel 1H-MRS of bilateral thalami in 27 ESRD patients who currently receiving hemodialysis treatment and 21 age-matched healthy volunteers. ESRD patients underwent Pittsburgh Sleep Quality Index (PSQI) scale and restless legs syndrome (RLS) rating scale assessment. Laboratory blood tests including serum creatinine, serum urea, cystatin-C, serum parathyroid hormone (PTH), calcium and phosphorus levels, hemoglobin and hematocrit were performed in all ESRD patients close to the time of the MR examination. We found correlations among elevated PTH, higher PSQI score and RLS rating score in ESRD patients. ESRD patients displayed decreased N-acetylaspartate and creatine ratio (NAA/Cr) of thalami compared with controls. There were significantly negative correlation between NAA/Cr and serum PTH level or PSQI score. The metabolic changes of thalami played an important role in the neuropathological mechanisms of lower sleep quality in ESRD patients. Secondary hyperparathyroidism as one of the main uremia-related factors was closely related to abnormal metabolites of the thalamus in patients with ESRD, revealing the crosstalk procedure between renal impairment and brain function.
https://ift.tt/2xeZDbw
PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation
Abstract
Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.
https://ift.tt/2QycdLU
The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients
Abstract
It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU) negatively influences cognitive performance. Several tests have been used to study these functions. Until now, no universal, optimal tool has been developed for detecting PKU-caused brain dysfunctions. Using computerized neuropsychological tests during daily routine would be helpful for screening subclinical brain deficits in adult PKU patients. In a monocentric, cross-sectional study, adult patients with PKU (n = 46; median age = 29.5 years; female/male ratio = 21/25) were tested with the computerized Cambridge Cognition (CANTAB) test measuring neurocognitive functions. Patients were divided into two groups: The "on diet" group included patients whose blood Phe-level was under 600 μmol/l (n = 20), and the "loose diet" group included patients whose blood Phe-level was above 600 μmol/l (n = 26) at the examination time. The results of the PKU-affected individuals were compared with a healthy control group (n = 31; median age = 25 years; female/male ratio = 11/20). Compared with the control group, PKU patients had significantly worse test results in memory, problem-solving skills, and strategy. However, there were no significant differences in response speed or initial thinking time. There was no correlation between the blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different cognitive test results. There were no significant differences in test results between the two PKU subgroups. Several cognitive functions measured by CANTAB are negatively influenced by hyperphenylalaninemia in adult PKU patients. However, response speed and initial thinking time were not impaired as seriously as other functions. Patients with lower Phe-levels failed to achieve better test results than patients whose Phe-levels were notably elevated.
https://ift.tt/2Qxt0yD
Methylenetetrahydrofolate reductase C677T variant and hyperhomocysteinemia in subarachnoid hemorrhage patients from India
Abstract
Methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T, A1298C) has been implicated in increased plasma homocysteine (Hcy) levels. The present study was designed to investigate the association between MTHFR polymorphism and increased Hcy levels in subarachnoid haemorrhage (SAH) patients. A total of 150 subjects from North India were included in the study, comprising of 100 SAH patients and 50 healthy controls. Plasma Hcy levels was determined and MTHFR polymorphism (C677T, A1298C) was screened by High resolution melting (HRM) analysis. Plasma Hcy levels were found to be significantly higher (p < 0.001) in SAH patients than in healthy controls. No significant difference in the genotype and allele frequency of MTHFR A1298C was observed. However, frequency of MTHFR C677T genotype, CT (53% vs. 20%; p < 0.001) and TT (15% vs. 2%; p < 0.05) was significantly higher in SAH group as compared to healthy controls. The frequency of T allele (41.5% vs. 12%; p < 0.001) was also found to be higher in SAH patients in comparison to healthy controls. Furthermore, Hcy levels were higher in SAH patients with TT genotype than in patients having CT genotype, whereas CC genotype had lower Hcy levels. The study suggests that higher frequency of MTHFR C677T allele may contribute to etiopathology of SAH through increase in Hcy levels.
https://ift.tt/2xhKQgn
Novel action of vinpocetine in the prevention of paraquat-induced parkinsonism in mice: involvement of oxidative stress and neuroinflammation
Abstract
Parkinson's disease (PD) is a multifactorial chronic progressive neurodegenerative disease caused by age, genetic and environmental factors such as paraquat (PQT). PQT (a quartenary nitrogen herbicide) is implicated in some form of idiopathic PD. This study sought to investigate the protective effect of vinpocetine on paraquat-induced Parkinsonism in mice. Forty-eight male albino mice were randomly divided into 6 groups and treated orally as follows for 21 days; Group 1: vehicle normal (10 ml/kg), group 2: vehicle control (10 ml/kg); groups 3–5: vinpocetine (5, 10 or 20 mg/kg); group 6: vinpocetine (20 mg/kg). Animals in groups 2–5 were given PQT (10 mg/kg, i.p.) every 3 days for 3 weeks. The effect of treatments on spontaneous motor activity (open field test), muscle coordination (rotarod tests), cataleptic behaviour (bar test), and working memory (Y-maze test) were assayed. After the behavioural assay on day 21, the midbrain was isolated for estimation of oxidative stress and TNF-α. Intraperitoneal injection of paraquat significantly induced motor deficits, muscle incoordination, catalepsy and working memory impairment which was ameliorated by the pretreatment of mice with vinpocetine. In addition, paraquat injection caused marked increase in nitroso-oxidative stress markers with concomitant deficits in antioxidant enzymes activities (GSH and SOD) as well as induction of tumour necrotic factor-α (TNF-α) in the mid-brain which were attenuated by the pretreatment of mice with vinpocetine. Findings from this study showed that vinpocetine prevented paraquat-induced motor deficits, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of neuroinflammatory cytokine. Thus, could be a potential drug in the management of Parkinsonism.
https://ift.tt/2xiN0vX
An Optimized Procedure to Develop a Three Dimensional Microfluidic Hydrogel with Parallel Transport Networks
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Nbfdjj
Genetic screening for macular dystrophies in patients clinically diagnosed with dry age‐related macular degeneration
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MwSNE1
Hepatocyte‐specific β‐catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2D0M7hY
Chronic alcohol consumption increases inflammation and osteoclastogenesis in apical periodontitis
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p8lC0f
“Letter To Editor: Terlipressin is Superior to Noradrenaline in the Management of Acute Kidney Injury in Acute On Chronic Liver Failure”
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p7IP2w
Inflammation and microbiota fingerprint: Delphi's oracle for NAFLD‐related HCC?
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p8wfQz
The interstitial space takes shape
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2D033oI
Biophysical screening methods for extracellular domain peptide receptors, application to natriuretic peptide receptor C ligands
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MwZvtu
Design, Synthesis and Biological Activity Evaluation of Campthothecin‐HAA‐Norcantharidin Conjugates as Antitumor Agents in Vitro
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p9hP2w
A propeller‐like small molecule as a novel G‐quadruplex DNA binder: The study of fluorescent sensing property and preferential interactions with human Telo21 structure
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MxoA7J
Secochililiode ester derivatives: preparation and evaluation of their antitrypanosomal and antimalarial efficacy
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p7IbC8
In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5‐HT2 and α1 receptors
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MyXXiG
Technetium‐99m radiolabeling and biological study of epirubicin for in vivo imaging of multi‐drug resistant Staphylococcus aureus infection via single‐photon emission computed tomography
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2p8OZzm
Cinnamic acids derived compounds with antileishmanial activity target Leishmania amazonensis arginase
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Mv9iAd
Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2D0AfMO
Boosting Photovoltaic Output of Ferroelectric Ceramics by Optoelectric Control of Domains
Advanced Materials, EarlyView.
https://ift.tt/2Ncc5Ue
Anomalous Photovoltaic Effect in Centrosymmetric Ferroelastic BiVO4
Advanced Materials, EarlyView.
https://ift.tt/2CVoN50
Pressure/Temperature Sensing Bimodal Electronic Skin with Stimulus Discriminability and Linear Sensitivity
Advanced Materials, EarlyView.
https://ift.tt/2CVop6y
A Ternary Ni46Co40Fe14 Nanoalloy‐Based Oxygen Electrocatalyst for Highly Efficient Rechargeable Zinc–Air Batteries
Advanced Materials, EarlyView.
https://ift.tt/2NfmOx5
Direct Chirality Recognition of Single‐Crystalline and Single‐Walled Transition Metal Oxide Nanotubes on Carbon Nanotube Templates
Advanced Materials, EarlyView.
https://ift.tt/2CVonvs
High Mobilities in Layered InSe Transistors with Indium‐Encapsulation‐Induced Surface Charge Doping
Advanced Materials, EarlyView.
https://ift.tt/2Nhr8Mo
Solid Halide Electrolytes with High Lithium‐Ion Conductivity for Application in 4 V Class Bulk‐Type All‐Solid‐State Batteries
Advanced Materials, EarlyView.
https://ift.tt/2CZmNsx
Bidirectional Transformation Enables Hierarchical Nanolaminate Dual‐Phase High‐Entropy Alloys
Advanced Materials, EarlyView.
https://ift.tt/2NbiNtA
Organic‐Single‐Crystal Vertical Field‐Effect Transistors and Phototransistors
Advanced Materials, EarlyView.
https://ift.tt/2CVoebo
Large‐Area Synthesis of Layered HfS2(1−x)Se2x Alloys with Fully Tunable Chemical Compositions and Bandgaps
Advanced Materials, EarlyView.
https://ift.tt/2NgSVN6
A Novel Strategy for Scalable High‐Efficiency Planar Perovskite Solar Cells with New Precursors and Cation Displacement Approach
Advanced Materials, EarlyView.
https://ift.tt/2CZmA8J
Impact of 2‐Ethylhexyl Stereoisomers on the Electrical Performance of Single‐Crystal Field‐Effect Transistors
Advanced Materials, EarlyView.
https://ift.tt/2NbbEtr
Mechanochemically Assisted Synthesis of a Ru Catalyst for Hydrogen Evolution with Performance Superior to Pt in Both Acidic and Alkaline Media
Advanced Materials, EarlyView.
https://ift.tt/2CWQU3G
Chemical Vapor Deposition Grown Wafer‐Scale 2D Tantalum Diselenide with Robust Charge‐Density‐Wave Order
Advanced Materials, EarlyView.
https://ift.tt/2NfsUhc
Organic Long‐Persistent Luminescence from a Flexible and Transparent Doped Polymer
Advanced Materials, EarlyView.
https://ift.tt/2CZmcHj
Lead‐Free Highly Efficient Blue‐Emitting Cs3Cu2I5 with 0D Electronic Structure
Advanced Materials, EarlyView.
https://ift.tt/2NhAS9B
Outcomes of Multidisciplinary Treatment Planning in US Cancer Care Settings
Cancer, EarlyView.
https://ift.tt/2NdhhHr
Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer
Abstract
Circulating cell-free DNA (cfDNA) has become a potential diagnostic and prognostic biomarker for colorectal cancer (CRC). In non-cancerous diseases, it has been confirmed that cfDNA can be recognized by Toll-like receptor 9 (TLR9), leading to a significant biological change. Nevertheless, the biological significance of cfDNA and its relationship with TLR9 in tumor malignancy is still unclear. Therefore, the purpose of this study is to explore the biological role of cfDNA in colorectal cancer (CRC). The expression of TLR9 was measured in different CRC cell lines and cancerous samples by RT-PCR or immunohistochemistry, which showed that high expression of TLR9 was significantly correlated with the tumor metastasis, advanced TNM stage and poor prognosis of patients. Then, cfDNA was obtained from fluorouracil (5FU)-induced apoptotic cancer cells in vitro and transfection techniques were used to transfect siRNA and cDNA plasmid for TLR9. Cancer cells were stimulated using isolated cfDNA fragments, and results showed that cfDNA could promote colorectal cancer cell proliferation via TLR9. Meanwhile, we demonstrated that the cfDNA binding to TLR9 could facilitate cell migration and invasion. Finally, we demonstrated that cfDNA initiated downstream TLR9-MyD88 signaling and induced robust release of chemokine interleukin 8 (IL-8), which helped to elucidate the mechanisms underlying these phenomena. Our data suggest that cancer cell-derived cfDNA contributes to cancer progression through activation of TLR9-MyD88 signaling and IL-8 secretion in CRC. These findings provide a novel perspective for understanding of tumor progression and provoke a potential therapeutic target for CRC treatment.https://ift.tt/2p6NPnU
Prophylactic treatment against GM‐CSF, but not IL‐17, abolishes relapses in a chronic murine model of multiple sclerosis
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Mz9rTc
Pseudoprogression with subsequent complete response and severe thrombocytopenia to checkpoint inhibitor immunotherapy in a patient with advanced mucosal melanoma of the sinonasal cavity
In this case report, we describe a patient with an inoperable mucosal melanoma of the sinonasal cavity who achieved an ongoing complete response to combined immunotherapy with ipilimumab and nivolumab after initial pseudoprogression. Despite massive enlargement of the tumor 9 weeks after treatment initiation, we decided to continue with checkpoint inhibitor immunotherapy because of lacking potent therapeutic alternatives and the possibility of pseudoprogression. In the computed tomography scan 3 months later, the tumor was no longer detectable. To date, the patient is still in remission. However, she developed severe immune-related thrombocytopenia and neutropenia that are rarely encountered with checkpoint inhibitor immunotherapy. Thrombocytopenia did not respond to corticosteroids, but rapidly improved after the administration of single-dose intravenous immunoglobulin. This exceptional case highlights the effectiveness of combined immunotherapy with ipilimumab and nivolumab in mucosal melanoma, the phenomenon of pseudoprogression, as well as the rare event of immune-related hematological side effects.https://ift.tt/2My0aLj
Imatinib-induced drug reaction with eosinophilia and systemic symptoms in solid tumors: a patient with dermatofibrosarcoma protuberans and successful desensitization management
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening drug-induced hypersensitivity reaction, characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with hypereosinophilia, and elevated liver function tests, which in severe cases may lead to fulminant hepatic failure and death. Although DRESS syndrome has been associated with over 50 different drugs including imatinib, it has never been reported in association with imatinib treatment in solid tumors. We recently treated a patient with metastatic dermatofibrosarcoma protuberans, a rare cutaneous mesenchymal tumor characterized by constitutive activation of the PDGFβ receptor and high sensitivity to imatinib therapy, who had a DRESS reaction to imatinib. Given an initial dramatic clinical and radiological response to treatment and lack of effective alternative targeted therapies, following imatinib discontinuation and resolution of DRESS, we cautiously reintroduced imatinib therapy using a desensitization protocol under the care of the allergy and immunologic clinic. Imatinib was carefully titrated from an initial dose of 50 mg to a target dose of 400 mg daily, while tapering down the prednisone dose. The patient was able to tolerate the treatment without recurrent episodes of DRESS or interruptions, and gained additional 6 months of clinical benefit from imatinib treatment. Although suspected causative drugs should not be reintroduced in DRESS whenever possible, in this case of metastatic disease and lack of effective alternative treatments, a carefully designed drug rechallenge helped minimize the risk of overt clinical reaction and resulted in an overall clinical benefit.https://ift.tt/2MyTP2a
Increased tacrolimus blood concentration by Beni‐Madonna – a new hybrid citrus cultivar categorized as ‘Tangor’, in a liver transplant patient: likely furanocoumarin‐mediated inhibition of CYP3A4 or P‐glycoprotein
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2CZjz8p
Issue Information
British Journal of Clinical Pharmacology, Volume 84, Issue 10, Page 2171-2172, October 2018.
https://ift.tt/2NenYJb
Issue highlights
British Journal of Clinical Pharmacology, Volume 84, Issue 10, Page 2173-2174, October 2018.
https://ift.tt/2CXuuj5
Oral Fluoroquinolones and Risk of Fibromyalgia
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2NenYsF
Extravasation accidents with liposomal/liposomal pegylated anthracyclines treated with dexrazoxane: an overview and outcomes
The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2–3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.https://ift.tt/2My0ucZ
Dual compartmental targeting of cell cycle and angiogenic kinases in colorectal cancer models
Cancer is a disease caused by several factors characterized by uncontrolled cell division, growth, and survival. ENMD-2076, is a novel orally active small molecule multikinase inhibitor targeting angiogenesis, proliferation, and the cell cycle. It is selectively active against the mitotic kinases aurora A and B, and kinases responsible for angiogenesis including VEGFR2/KDR and FGFR1 and 2. ENMD-2076 has been shown to inhibit tumor growth and prevent angiogenesis in vitro and in vivo in preclinical cancer models. Moreover, in a phase I trial, ENMD-2076 was well tolerated, exhibited a linear pharmacokinetic profile, and showed a promising antitumor activity in a number of solid tumors. In this study, we show that ENMD-2076 has antiproliferative effects, causes cell cycle arrest, and has activity in preclinical models of colorectal cancer (CRC), including patient-derived xenograft (PDX) models. Forty-seven human CRC cell lines were exposed in vitro to ENMD-2076 and analyzed for effects on cell cycle, apoptosis, and downstream effector proteins. The drug was then tested against 20 human CRC PDX models to further evaluate in-vivo antitumor activity. We show that ENMD-2076 exhibits a broad range of activity against a large panel of CRC cell lines with varying molecular characteristics. Mechanistically, ENMD-2076 exposure resulted in a G2/M cell cycle arrest, an increase in aneuploidy, and cell death in responsive cell lines. In addition, ENMD-2076 treatment resulted in a promising antitumor activity in CRC PDX models. These results support the continued development of ENMD-2076 in CRC including further exploration of rational combinations.https://ift.tt/2QCJZzI
A case of complete response to nivolumab after long-term progression-free survival with tyrosine kinase inhibitor
Nivolumab is an effective and tolerable treatment for metastatic renal cell carcinoma, showing longer median overall survival than everolimus and achieving a good percentage of objective response, stable disease, and prolonged responses. However, very few cases have been reported in the literature of a complete response to nivolumab in the metastatic pretreated setting. Here, we report a case of complete response to nivolumab in II line following sunitinib in a metastatic clear cell renal cell carcinoma with favorable risk according to the IMDC criteria. This is also an interesting case on the use of immunotherapy following a long period of antiangiogenetic therapy, underlining the importance of the sequence of treatment to achieve the best possible outcome in terms of prolonged overall survival, progression-free survival, and objective response.https://ift.tt/2My0rhj
B-cell lymphoma 2 ovarian killer suppresses testicular cancer cell malignant behavior, but plays a role in platinum resistance
Testicular cancer (TC) is the most common malignancy in men. Although the 5-year survival rate of TC patients exceeds 95%, the prognosis of patients with platinum-resistant tumors remains poor because of limited therapeutic options. Overcoming chemoresistance is the key to improving survival in poor-prognosis patients. However, the mechanism remains poorly understood. B-cell lymphoma 2 ovarian killer (BOK) is a proapoptotic protein and functions as a tumor suppressor in malignancy tumors. In this study, we found that BOK was frequently downregulated in TC tissues compared with paratumor tissues. BOK overexpression inhibited TC cell proliferation and invasion. In contrast, BOK knockdown promoted TC cell proliferation and invasion. Surprisingly, either BOK overexpression or knockdown rendered TC cells resistant to Cisplatin (DDP). In conclusion, BOK downregulation may be associated with tumorigenesis of TC. BOK had the potency to suppress TC cell proliferation and invasion, and may function as a tumor suppressor in TC. However, BOK also contributes to Cisplatin resistance. These data may provide a wider perspective on TC research and treatment.https://ift.tt/2QAyGrR
Inhibition of breast tumor growth in mice after treatment with ceramide analog 315
The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n=10) were injected bilaterally with 5×106 MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n=5 in each group). The control group mice were injected with 25 μl of dimethyl sulfoxide and the treatment group mice were injected with 10 mg/kg of analog 315 (in dimethyl sulfoxide, 25 μl volume) every day for a period of 3 weeks. Animal weights and tumors were measured every week for 3 weeks. At the end of the experimental period, control animals had retained excess fluid, and showed larger tumor sizes compared with the treated group (2.95 vs. 1.67 g). A 45% reduction in tumor size and 80% decrease in tumor volume were observed in the treatment group. There was a significant increase in the weights of liver (10%) and spleen (19%) between the control and treated animals. Hematoxylin and Eosin staining of MDA-MB-231 tumor sections revealed more acellular necrotic regions in tumors from the treatment groups compared with the ones from the control group. Ki67, a proliferation marker was higher in number in control tumor section (71.8±12.8) compared to the treatment tumor section (37.4±10.4) (Phttps://ift.tt/2My0n13
RITA induces apoptosis in p53-null K562 leukemia cells by inhibiting STAT5, Akt, and NF-κB signaling pathways
Targeting oncogenic signaling pathways by small molecules has emerged as a potential treatment strategy for cancer. reactivation of p53 and induction of tumor cell apoptosis (RITA) is a promising anticancer small molecule that reactivates p53 and induces exclusive apoptosis in tumor cells. Less well appreciated was the possible effect of small molecule RITA on p53-null leukemia cells. In this study, we demonstrated that RITA has potent antileukemic properties against p53-null chronic myeloid leukemia (CML)-derived K562 cells. RITA triggered apoptosis through caspase-9 and caspase-3 activation and poly (ADP-ribose) polymerase cleavage. RITA decreased STAT5 tyrosine phosphorylation, although it did not inhibit phosphorylation of the direct BCR-ABL substrate CrkL. Real-time PCR analysis showed that RITA downregulates antiapoptotic STAT5 target genes Bcl-xL and MCL-1. The downregulation of nuclear factor-κB (NF-κB), as evidenced by inhibition of IκB-α phosphorylation and its degradation, was associated with inhibition of Akt phosphorylation in RITA-treated cells. Furthermore, consistent with the decrease of mRNA levels, protein levels of the nuclear factor-κB-regulated antiapoptotic (cIAP1, XIAP, and Bcl-2) and proliferative (c-Myc) genes were downregulated by RITA in K562 cells. In conclusion, the ability of RITA to inhibit prosurvival signaling pathways in CML cells suggests a potential application of RITA in CML therapeutic protocols.https://ift.tt/2QrsKkN
Construction and characterization of regulated cycle inhibiting factors induced upon Tet-On system in human colon cancer cell lines
A previous study has proven that cycle inhibiting factors (Cifs) inhibit Cullin E3 ubiquitin ligases, resulting in cell cycle arrest. More importantly, Cifs are also involved in cancer progression by deamidating Nedd8. Here we aimed to explore a novel insight into the treatment implications of Cifs in colon cancers by Tet-on system. The anticancer activity of Cif by doxycycline induction was investigated in the colon cell lines based upon Tet-On system. The expression of Cif in the colon cancer cells was determined by western blot. Furthermore, the cell viability and flow cytometry analysis were respectively performed to evaluate the cell proliferation and survival of colon cells. More importantly, the p21 and p27 levels were also evaluated after the induction of Cif with Tet-On system. Multiple clones of colon cancer cells for doxycycline-regulated Cif expression were constructed for maintenance purposes including HCT116 and SW480 cell lines. The result of western blot displayed good inducibility of expressing Cif in the cell lines. The clones with CifWT preserved their transformed phenotype compared with the control group (clones with GFP or with CifC/A), in terms of the inhibition of cancer cell proliferation and survival. Furthermore, western blot analysis showed that p27 and p21 were accumulated in the clones with CifWT, compared with the colon cancer cell lines with GFP or with CifC/A. Using the Tet-On system, we developed an efficient approach toward generation of colon cancer cells induced with Cif. These engineered colons tightly controlled Cif expression in vitro, which is a good inducible model system for cancer treatment.https://ift.tt/2QyOAmy
Plumbagin inhibits the proliferation of nasopharyngeal carcinoma 6-10B cells by upregulation of reactive oxygen species
Plumbagin (PLB) is the primary component of the traditional Chinese medicine Baihua Dan, and possesses anti-infection and anticancer effects, with the ability to enhance the sensitivity of tumor cells to radiation therapy. However, the anticancer effect of PLB on nasopharyngeal carcinoma and the underlying mechanisms remain unclear. In this study, we investigated the anticancer effects of PLB on nasopharyngeal carcinoma 6-10B cells and clarified its molecular mechanisms in vitro. The results showed that PLB was effective against 6-10B cells proliferation in a dose-dependent manner by inducing G2/M phase cell cycle arrest. Furthermore, our data showed that PLB induced reactive oxygen species accumulation, which inhibited the GSK3β/STAT3 pathway and arrested the G2/M phase. Therefore, our results provided new insight into the mechanism of the antitumor effects of PLB, supporting PLB as a prospective therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox balance.https://ift.tt/2My0hGJ
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
