Is violence in part a lithium deficiency state?

Publication date: Available online 10 February 2016
Source:Medical Hypotheses
Author(s): Mark R. Goldstein, Luca Mascitelli
Violence, particularly firearm violence, leading to suicide and homicide is a significant problem worldwide. A majority of suicidal and homicidal violence involves males; homicidal violence is prevalent among young men and suicide is the leading cause of violence worldwide. Lithium, in pharmacological doses, has been used successfully for decades in treating bipolar disorders, and has been shown to decrease violent crime in this situation. Interestingly, lithium, in trace amounts, as occurs in some drinking water, has been inversely related to aggression, and suicidal and homicidal violence. Lithium is naturally found in vegetables, grains and drinking water, and dietary intake varies from nearly zero to 3 mg daily. Elemental lithium, in trace doses, has been shown to improve mood in weeks. Moreover, lithium, in trace amounts, has no toxicity. In order to ensure adequate dietary intakes of elemental lithium daily for the purpose of decreasing aggression and violence, we propose considering the fortification of cereal grain products with lithium and also the addition of lithium to vitamin preparations for adults. Importantly, randomized trials in various populations are needed to test this hypothesis.



from #Medicine via ola Kala on Inoreader http://ift.tt/1SI1DQr
via IFTTT

A hybrid fever therapy for increased tumor selectivity

Publication date: Available online 10 February 2016
Source:Medical Hypotheses
Author(s): Garry Noe
Lipopolysaccharide (LPS), mediator of the Coley and Shwartzman fever therapies, is a potent endotoxin capable of inducing sepsis at moderate intravenous doses, which currently limits its experimental and clinical use. By exploiting elevated G-CSF concentrations and neutrophil numbers within tumors, it may be possible to selectively trigger a sepsis-like syndrome in malignant tissues using only moderate hyperthermia and low-dose LPS, leaving normal organs unaffected. Analogous to the organ failure that can result from severe sepsis, repeated application of the proposed procedure could lead to tumor necrosis and regression. Biomarkers including heat shock proteins and circulating endothelial cells, and intravital microscopy of intravascular NETs, microthrombi, and bleeding in tumors can be used to test predicted consequences of this therapy. The two components of this hybrid approach, hyperthermia and acute but mild endotoxemia, could provide a tumor-specific therapeutic modality with relatively mild side effects, and therefore permit repeated application over an extended treatment period.



from #Medicine via ola Kala on Inoreader http://ift.tt/1PkGjMP
via IFTTT

Autologous Tumor Immunizing Devascularization in cancer therapy

Publication date: Available online 10 February 2016
Source:Medical Hypotheses
Author(s): Vladimir Kalina, David J. Kopsky
Tumor vaccination depending on specific antigens, autologous tumor vaccination involving wide range of antigens, immunomodulating cytokines and bacterial agents have been studied extensively with the purpose of stimulating the antitumor immune response. Unfortunately these therapies showed disappointing results mainly due to undesirable mechanisms tending to dampen the antitumor immune response. We will discuss a novel approach of autologous tumor immunization using a surgical technique: autologous tumor immunizing devascularization (ATID). This approach involves complete surgical devascularization of a tumor which is then left isolated in situ in the body. The stressing pathophysiological condition of the completely isolated tumor provokes a generalized immune response which, as shown from clinical cases, leads to the elimination of the devascularized tumor and distant metastases without causing sepsis. Until now no clinical study was properly executed. The possible significance of this method which resides in its curative potential has thus escaped attention in the field of cancer therapy. This article will hypothesize optimal physiological criteria and necessary clinical conditions for ATID to be performed effectively. The main criteria are 1) complete isolation of the tumor from the vascular system, 2) sufficient devascularized tumor load to trigger a sustained generalized immune response to cancer antigens until elimination of all cancer loci, 3) tumor cell killing rate corresponding to the elicited immune response is higher than the tumor cell growth rate, and 4) patients with an uncompromised immune system. Future studies have to be performed under the indicated conditions in order to confirm the efficacy and safety of ATID as a novel approach in the treatment of cancer.



from #Medicine via ola Kala on Inoreader http://ift.tt/1SI1BYK
via IFTTT

Salt and miscarriage: is there a link?

Publication date: Available online 9 February 2016
Source:Medical Hypotheses
Author(s): Amir Abdoli
Salt is a major mineral element that plays fundamental roles in health and disease. Excessive salt intake is a major cause of hypertension, cardiovascular disease and stroke. Miscarriage and preeclampsia are the most common pregnancy complications with multiple etiological factors, including inflammatory and autoimmune conditions. More recently, different studies indicated that excessive salt intake is involved in the development of inflammatory processes through induction of T helper-17 pathway and their inflammatory cytokines. On the other hand, several studies indicated the pivotal role of inflammation in the etiology of miscarriage, preeclampsia and adverse pregnancy outcome. Here, it is hypothesized that excessive salt intake around the time of conception or during pregnancy can trigger inflammatory processes, which consequently associated with increased risk of miscarriage, preeclampsia or adverse pregnancy outcome. Thus, this hypothesis suggests that low salt intake around the time of conception or during pregnancy can decrease the risk of miscarriage or adverse pregnancy outcome. This hypothesis also offers new insights about the role of salt in the etiology of miscarriage and preeclampsia.



from #Medicine via ola Kala on Inoreader http://ift.tt/1QVeuen
via IFTTT

Proteome analysis of Bordetella pertussis isolated from human macrophages

Publication date: Available online 10 February 2016
Source:Journal of Proteomics
Author(s): Yanina Lamberti, Juan Hilario Cafiero, Kristin Surmann, Hugo Valdez, Jana Holubova, Večerek Branislav, Peter Sebo, Frank Schmidt, Uwe Völker, Maria Eugenia Rodriguez

Graphical abstract

from #Medicine via ola Kala on Inoreader http://ift.tt/1PkGlUE
via IFTTT

Catalysts, Vol. 6, Pages 27: Highly Efficient Cationic Palladium Catalyzed Acetylation of Alcohols and Carbohydrate-Derived Polyols

The development of a new facile method for the acetylation of alcohols and carbohydrate-derived polyols is described. This method relies on the nature of the cationic palladium catalyst, Pd(PhCN)2(OTf)2 which is generated in situ from Pd(PhCN)2Cl2 and AgOTf to catalyze the acetylation reaction. This new acetylation protocol is very rapid and proceeds under mild conditions with only 1 mol% of catalyst loading at room temperature. This new method has been applied to a variety of different alcohols with different levels of steric hindrance, as well as carbohydrate-derived polyols to provide the corresponding fully acetylated products in excellent yields.

from #Medicine via ola Kala on Inoreader http://ift.tt/1V3eTwq
via IFTTT

Polymers, Vol. 8, Pages 47: Developed Hybrid Model for Propylene Polymerisation at Optimum Reaction Conditions

A statistical model combined with CFD (computational fluid dynamic) method was used to explain the detailed phenomena of the process parameters, and a series of experiments were carried out for propylene polymerisation by varying the feed gas composition, reaction initiation temperature, and system pressure, in a fluidised bed catalytic reactor. The propylene polymerisation rate per pass was considered the response to the analysis. Response surface methodology (RSM), with a full factorial central composite experimental design, was applied to develop the model. In this study, analysis of variance (ANOVA) indicated an acceptable value for the coefficient of determination and a suitable estimation of a second-order regression model. For better justification, results were also described through a three-dimensional (3D) response surface and a related two-dimensional (2D) contour plot. These 3D and 2D response analyses provided significant and easy to understand findings on the effect of all the considered process variables on expected findings. To diagnose the model adequacy, the mathematical relationship between the process variables and the extent of polymer conversion was established through the combination of CFD with statistical tools. All the tests showed that the model is an excellent fit with the experimental validation. The maximum extent of polymer conversion per pass was 5.98% at the set time period and with consistent catalyst and co-catalyst feed rates. The optimum conditions for maximum polymerisation was found at reaction temperature (RT) 75 °C, system pressure (SP) 25 bar, and 75% monomer concentration (MC). The hydrogen percentage was kept fixed at all times. The coefficient of correlation for reaction temperature, system pressure, and monomer concentration ratio, was found to be 0.932. Thus, the experimental results and model predicted values were a reliable fit at optimum process conditions. Detailed and adaptable CFD results were capable of giving a clear idea of the bed dynamics at optimum process conditions.

from #Medicine via ola Kala on Inoreader http://ift.tt/1o2qqlm
via IFTTT

Protective Role of Sodium–Glucose Co-Transporter 2 Inhibition Against Vascular Complications in Diabetes

Rejuvenation Research , Vol. 0, No. 0.


from #Medicine via ola Kala on Inoreader http://ift.tt/1Q8CGwY
via IFTTT

Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques

Journal of Interferon & Cytokine Research , Vol. 0, No. 0.


from #Medicine via ola Kala on Inoreader http://ift.tt/1T6Viwb
via IFTTT

Operational method of solution of linear non-integer ordinary and partial differential equations

We propose operational method with recourse to generalized forms of orthogonal polynomials for solution of a variety of differential equations of mathematical physics. Operational definitions of generalized families of orthogonal polynomials are used in this context. Integral transforms and the operational exponent together with some special functions are also employed in the solutions. The examples of solution of physical problems, related to such problems as the heat propagation in various models, evolutional processes, Black–Scholes-like equations etc. are demonstrated by the operational technique.PACS Nos.: 02.30 Gp, Hq, Jr, Mv, Nw, Tb, Uu, Vv, Zz, 41.85.Ja, 03.65.Db, 05.60.Cd.

from #Medicine via ola Kala on Inoreader http://ift.tt/1KbtkxX
via IFTTT

Evaluation of wild herbivore faeces from South Africa as a potential source of hydrolytically active microorganisms

This study assessed faecal matter from three indigenous South African herbivores—zebra, giraffe and impala—as a potential source for hydrolytically active aerobic and facultatively anaerobic bacteria. Herbivore droppings were collected freshly in a local nature reserve in Pietermaritzburg, South Africa. Soil samples adjacent to faecal collection sites and faeces from a domestic herbivore, the Nguni cow, were included as controls. Hydrolase and dehydrogenase activity in faecal matter and soil samples were measured by the fluorescein diacetate and the triphenyltetrazolium chloride assay. Viable counts and counts for amylase, cellulase, esterase and protease producers were established using plate count agar and solid media containing cellulose, skim milk, starch and Tween 80. Zebra droppings produced the highest hydrolase and dehydrogenase activity. Faecal matter of the three indigenous herbivores generally produced higher hydrolytic activity than Nguni cow faeces and soil controls, thereby confirming that these materials are potential targets for hydrolytic enzyme mining.

from #Medicine via ola Kala on Inoreader http://ift.tt/1V39EwH
via IFTTT

Integrated measures for rough sets based on general binary relations

Uncertainty measures are important for knowledge discovery and data mining. Rough set theory (RST) is an important tool for measuring and processing uncertain information. Although many RST-based methods for measuring system uncertainty have been investigated, the existing measures cannot adequately characterise the imprecision of a rough set. Moreover, these methods are suitable only for complete information systems, and it is difficult to generalise methods for complete information systems to incomplete information systems. To overcome these shortcomings, we present new uncertainty measures, integrated accuracy and integrated roughness, that are based on general binary relations, and we study important properties of these measures. A theoretical analysis and examples show that the proposed integrated measures are more precise than existing uncertainty measures, they are suitable for both complete and incomplete information systems, and they are logically consistent. Therefore, integrated accuracy and integrated roughness overcome the limitations of existing measures. This research not only develops the theory of uncertainty, it also expands the application domain of uncertainty measures and provides a theoretical basis for knowledge acquisition in information systems based on general binary relations.

from #Medicine via ola Kala on Inoreader http://ift.tt/1Kbti9v
via IFTTT

Issue Information - TOC

No abstract is available for this article.

from #Medicine via ola Kala on Inoreader http://ift.tt/1QV89zE
via IFTTT

Issue Information - JIF

No abstract is available for this article.

from #Medicine via ola Kala on Inoreader http://ift.tt/1KEYHB6
via IFTTT

Comment on “Ventricular non-compaction cardiomyopathy: prenatal diagnosis and pathology”

from #Medicine via ola Kala on Inoreader http://ift.tt/1QV89ja
via IFTTT

Increased nuchal translucency and pregnancy outcome: a retrospective study of 1063 consecutive singleton pregnancies in a single referral institution

from #Medicine via ola Kala on Inoreader http://ift.tt/1QV89j0
via IFTTT

A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma

Annals of Oncology

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSQRW
via IFTTT

Metabolic effect of pancreatoduodenectomy: Resolution of diabetes mellitus after surgery

Pancreatology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUeGk
via IFTTT

Evaluation of advanced fibrosis measured by transient elastography after hepatitis C virus protease inhibitor-based triple therapy

European Journal of Gastroenterology & Hepatology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUeGe
via IFTTT

Prevention of necrotizing enterocolitis through manipulation of the intestinal microbiota of the premature infant

Clinical Therapeutics

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSPxp
via IFTTT

MiR-143 inhibits tumor cell proliferation and invasion by targeting STAT3 in esophageal squamous cell carcinoma

Cancer Letters

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUbKB
via IFTTT

Levofloxacin, bismuth, amoxicillin and esomeprazole as second-line Helicobacter pylori therapy after failure of non-bismuth quadruple therapy

Digestive and Liver Diseases

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUepH
via IFTTT

Antibacterial gauzes are effective in preventing infections after percutaneous endoscopic gastrostomy placement: a retrospective analysis

European Journal of Gastroenterology & Hepatology

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSQBC
via IFTTT

Hepatocellular carcinoma in children: does modified platinum- and doxorubicin-based chemotherapy increase tumor resectability and change outcome? lessons learned from the SIOPEL 2 and 3 studies

Journal of Clinical Oncology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUepz
via IFTTT

The variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent

Gastroenterology

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSQlc
via IFTTT

Multiple HBV quasispecies and immune-escape mutations are present in HBV surface antigen and reverse transcriptase of patients with acute hepatitis B

The Journal of Infectious Diseases

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUe9h
via IFTTT

The clinical management of abdominal ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: a review of current guidelines and recommendations

European Journal of Gastroenterology & Hepatology

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSQl1
via IFTTT

CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine vs gemcitabine alone in patients with metastatic pancreatic cancer

Annals of Oncology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUe99
via IFTTT

Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: A multicenter prospective study

The American Journal of Gastroenterology

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSOK5
via IFTTT

Clinical and immunologic features of ultra-short celiac disease

Gastroenterology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUbdF
via IFTTT

Predicting the Occurrence of Hypotension in Stable Patients With Nonvariceal Upper Gastrointestinal Bleeding: Point-of-Care Lactate Testing

The Journal of Emergency Medicine

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSQ4r
via IFTTT

Randomized controlled trial of intraportal chemotherapy combined with adjuvant chemotherapy (mFOLFOX6) for stage II and III colon cancer

Annals of Surgery

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUbdD
via IFTTT

Adverse events of gastric electrical stimulators recorded in the Manufacturer and User Device Experience (MAUDE) Registry

Autonomic Neuroscience: Basic and Clinical

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSOts
via IFTTT

Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies

Annals of Surgery

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSOd5
via IFTTT

Diabetes-associated variation in TCF7L2 is not associated with hepatic or extrahepatic insulin resistance

Diabetes

from #Medicine via ola Kala on Inoreader http://ift.tt/20KSOd2
via IFTTT

Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation

European Journal of Gastroenterology & Hepatology

from #Medicine via ola Kala on Inoreader http://ift.tt/1WdUbdp
via IFTTT

Highly Efficient and Selective Isolation of Rare Tumor Cells Using a Microfluidic Chip with Wavy-herringbone Micro-patterned Surfaces

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00236F, Paper

Shunqiang Wang, Antony Thomas, Elaine Lee, Shu Yang, Xuanhong Cheng, Yaling Liu
Circulating tumor cells (CTCs) in peripheral blood have been recognized as a general biomarker for diagnosing cancer and providing guidance for personalized treatments. Yet due to their rarity, the challenge...
The content of this RSS Feed (c) The Royal Society of Chemistry

from #Medicine via ola Kala on Inoreader http://ift.tt/1KET1Hf
via IFTTT

The use of brief post-surgical low frequency electrical stimulation to enhance nerve regeneration in clinical practice

Abstract

Despite efforts to enhance peripheral nerve regeneration, there has been little progress in improving clinical outcomes. Recently, a method of brief post-surgical low frequency electrical stimulation of surgically repaired nerves has been developed. It was shown to accelerate axon outgrowth across the repair site and hastened target reinnervation. In this brief review, we describe the mechanistic insights and functional impacts of the post-surgical electrical stimulation that have been gained through animal studies. Brain derived neurotrophic factor, cyclic AMP and regeneration-associated genes play a vital role in expediting the outgrowth of axons across the injury site. The method of stimulation has also been shown to be effective in patients with severe compressive neuropathy as well as those with digital nerve laceration. Its clinical feasibility and positive impact open the door of further clinical translation in other peripheral nerve injuries.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1Tc1sN0
via IFTTT

Electrical synapses and the development of inhibitory circuits in the thalamus

Abstract

Neurons within the mature thalamic reticular nucleus (TRN) powerfully inhibit ventrobasal (VB) thalamic relay neurons via GABAergic synapses. TRN neurons are also coupled to one another by electrical synapses that depend strongly on the gap junction protein connexin36 (Cx36). Electrical synapses in the TRN precede the postnatal development of TRN-to-VB inhibition. We investigated how the deletion of Cx36 affects the maturation of TRN and VB neurons, electrical coupling, and GABAergic synapses by studying wild-type (WT) and Cx36 knockout (KO) mice. The incidence and strength of electrical coupling in TRN was sharply reduced, but not abolished, in KO mice. Surprisingly, electrical synapses between Cx36-KO neurons had faster voltage-dependent decay kinetics and conductance asymmetry (rectification) than did electrical synapses between WT neurons. The properties of TRN-mediated inhibition in VB also depended on Cx36 genotype. Deletion of Cx36 increased the frequency and shifted the amplitude distributions of miniature inhibitory postsynaptic currents (IPSCs), while the paired-pulse ratio of evoked IPSCs was unaffected, suggesting that the absence of Cx36 led to an increase in GABAergic synaptic contacts. VB neurons from Cx36-KO mice also tended to have simpler dendritic trees and fewer divergent inputs from the TRN, compared to WT cells. Our findings suggest that proper development of thalamic inhibitory circuitry, neuronal morphology, TRN cell function, and electrical coupling requires Cx36. In the absence of Cx36, some TRN neurons express asymmetric electrical coupling mediated by other, unidentified, connexin subtypes.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1V32dWt
via IFTTT

The repair Schwann cell and its function in regenerating nerves

Abstract

Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialised to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de-differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury-induced Schwann cell reprogramming involves down-regulation of myelin genes combined with activation of set of repair-supportive features, including up-regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair program is controlled transcriptionally by mechanisms involving the transcription factor c-Jun, which is rapidly up-regulated in Schwann cells after injury. In the absence of c-Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c-Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non-myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1Tc1tAp
via IFTTT

Fragile X mental retardation protein controls ion channel expression and activity

Abstract

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (Kv3.1 & Kv4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA-regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Cav2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1V32bOh
via IFTTT

The role of Orai/STIM calcium channels in melanocytes and melanoma

Abstract

Calcium signalling within normal and cancer cells regulates many important cellular functions such as migration, proliferation, differentiation and cytokine secretion.  Store operated Ca²⁺ entry (SOCE) via the Ca²⁺ release activated Ca²⁺ (CRAC) channels, which are composed of the plasma membrane based Orai channels and the endoplasmic reticulum stromal interaction molecules (STIMs), is a major Ca²⁺- entry route in many cell types. Orai and STIM have been implicated in the growth and metastasis of multiple cancers; however, while their involvement in cancer is presently indisputable, how Orai/STIM-controlled Ca²⁺ signals affect malignant transformation, tumor growth, and invasion is not fully understood. Here, we review recent studies linking Orai/STIM Ca²⁺ channels with cancer, with a particular focus on melanoma. We highlight and examine key molecular players and the signalling pathways regulated by Orai and STIM in normal and malignant cells, we expose discrepancies, and we reflect on the potential of Orai/STIMs as anticancer drug targets. Finally, we discuss the functional implications of future discoveries in the field of Ca²⁺ signalling.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1Tc1sMP
via IFTTT

Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation

Abstract

Vascular smooth muscle cell (VSMC) phenotypic conversion from a contractile to «synthetic» state contributes to vascular pathologies including restenosis, atherosclerosis and vascular calcification. We have recently found that the secretion of exosomes is a feature of "synthetic" VSMCs and that exosomes are novel players in vascular repair processes as well as pathological vascular thrombosis and calcification. Pro-inflammatory cytokines and growth factors as well as mineral imbalance stimulate exosome secretion by VSMCs, most likely by the activation of sphingomyelin phosphodiesterase 3 (SMPD3) and cytoskeletal remodeling. Calcium stress induces dramatic changes in VSMC exosome composition and accumulation of phosphatidylserine (PS), Annexin A6 and MMP2, which converts exosomes into a nidus for calcification. In addition, by presenting PS, VSMC exosomes can also provide the catalytic surface for the activation of coagulation factors. Recent data showing that VSMC exosomes are loaded with proteins and miRNA regulating cell adhesion and migration highlight VSMC exosomes as potentially important communication messengers in vascular repair. Thus, the identification of signalling pathways regulating VSMC exosome secretion, including activation of SMPD3 and cytoskeletal rearrangements, opens up novel avenues for a deeper understanding of vascular remodeling processes.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1V32dFW
via IFTTT

Experimental Investigation of Urethral Tissues and Structures Biomechanics

Urinary dysfunction can lead to incontinence, with relevant impact on the quality of life. This severe dysfunction can be surgically overcome by using an artificial urinary sphincter. However, several complications may result from an inappropriate prosthesis functionality, in many cases due to an unsuitable mechanical action of the device on urethral tissues. Computational models allow the investigation of mechanical interaction between biological tissues and biomedical devices, representing a potential support for surgical practice and prosthesis design. The development of such computational tools requires experimental data on biological tissues and structures mechanics, which are rarely reported in the literature. The present activities aim at providing a procedure for the mechanical characterization of urethral tissues and structures. The experimental protocol includes the morphometric and histologic analysis of urethral tissues, the mechanical characterization of tissues response by tensile and stress relaxation tests and the evaluation of urethral structural behavior by inflation tests. Results from preliminary experimental activities are processed adopting specific model formulations, also providing the definition of parameters that identify elastic and viscous tissues behavior. Different experimental protocols, leading to a comprehensive set of experimental data, allow for a reciprocal assessment of reliability of the investigation approach.

This article is protected by copyright. All rights reserved

from #Medicine via ola Kala on Inoreader http://ift.tt/1PksSwe
via IFTTT

IJMS, Vol. 17, Pages 231: Selenoprotein R Protects Human Lens Epithelial Cells against d-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress

Selenium is an essential micronutrient for humans. Much of selenium's beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells.

from #Medicine via ola Kala on Inoreader http://ift.tt/1SfmuKj
via IFTTT

IJMS, Vol. 17, Pages 230: Endocannabinoids as Guardians of Metastasis

Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain. Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer. The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis.

from #Medicine via ola Kala on Inoreader http://ift.tt/1TRBAp3
via IFTTT