Opening the Blood-Brain Barrier and Improving the Efficacy of Temozolomide Treatments of Glioblastoma Using Pulsed, Focused Ultrasound with a Microbubble Contrast Agent

Objective. To explore the effects of pulsed, focused, and microbubble contrast agent-enhanced ultrasonography (mCEUS) on blood-brain barrier (BBB) permeability and the efficacy temozolomide for glioblastoma. Methods. Wistar rats (n = 30) were divided into three groups (n = 10 per group) to determine optimal CUES conditions for achieving BBB permeability, as assessed by ultrastructure transmission electron microscopy (TEM) and western blot assays for the tight junction protein claudin-5. Optimized mCEUS effects on BBB permeability were subsequently confirmed with Evans blue staining (2 groups of 10 rats). The glioma cell line 9L was injected into the brain striatum of Wistar rats. After temozolomide chemotherapy, we detected glial fibrillary acidic protein (GFAP) levels in serum by enzyme-linked immunosorbent assay (ELISA) and in brain tissue by western blot, immunocytochemistry, and real-time quantitative polymerase chain reaction (qPCR). Results. BBB permeability was maximized with 1 ml/kg contrast agent mCEUS delivered via 10-min intermittent launches with a 400-ms interval. Evans blue staining confirmed BBB permeability following ultrasonic cavitation in the control group (P

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Plumbagin-Loaded Nanoemulsion Drug Delivery Formulation and Evaluation of Antiproliferative Effect on Prostate Cancer Cells

Background. Plumbagin, a medicinal plant-derived 5-hydroxy-2-methyl-1,4-naphthoquinone, is an emerging drug with a variety of pharmacological effects, including potent anticancer activity. We have previously shown that plumbagin improves the efficacy of androgen deprivation therapy (ADT) in prostate cancer and it is now being evaluated in phase I clinical trial. However, the development of formulation of plumbagin as a compound with sparing solubility in water is challenging. Methods. We have formulated plumbagin-loaded nanoemulsion using pneumatically controlled high pressure homogenization of oleic acid dispersions with polyoxyethylene (20) sorbitan monooleate as surfactant. Nanoemulsion formulations were characterized for particle size distribution by dynamic light scattering (DLS). The kinetics of in vitro drug release was determined by equilibrium dialysis. Anticancer activity toward prostate cancer cells PTEN-P2 was assessed by MTS (Owen's reagent) assay. Results. Particle size distribution of nanoemulsions is tunable and depends on the surfactant concentration. Nanoemulsion formulations of plumbagin with 1-3.5% (w/w) of surfactant showed robust stability of size distribution over time. Plumbagin-loaded nanoemulsion with average hydrodynamic diameter of 135 nm showed exponential release of plumbagin with a half-life of 6.1 h in simulated gastric fluid, 7.0 h in simulated intestinal fluid, and displayed enhanced antiproliferative effect toward prostate cancer cells PTEN-P2 compared to free plumbagin. Conclusion. High drug-loading capacity, retention of nanoparticle size, kinetics of release under simulated physiological conditions, and increased antiproliferative activity indicate that oleic-acid based nanoemulsion formulation is a suitable delivery system of plumbagin.

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Immunoglobulin E and G Levels in Predicting Minimal Change Disease before Renal Biopsy

Purpose. The diagnosis of minimal change disease in adults relies mainly on renal biopsy, but this procedure is not without complications. Despite the advancements in technique of percutaneous renal biopsy, biopsy-related complications still occur. Bleeding is one of the major complications, which may lead to hemodynamic instability and, sometimes, even death. Thus, we developed a model to predict MCD for high-risk patients unsuitable for renal biopsy. Methods. We enrolled 142 patients with nephrotic syndrome who received renal biopsy between October 2007 and April 2011 at one tertiary medical center in this study. Demographic, clinical, and prebiopsy laboratory variables were retrospectively recorded and analyzed. Results. The overall prevalence of MCD was 26.8%. Age, hemoglobin levels, 24-hour urine protein, immunoglobulin (Ig) G, and IgE differed significantly between the MCD and non-MCD groups. Logistic regression analysis showed a significant increase in the risk of developing MCD as the number of Ig risk factors, namely, IgG 110 mg/dl, increased. Having both risk factors significantly increased the chances of receiving a diagnosis of MCD (by 31.84-fold, P =.007) compared with having neither. Combining the aforementioned clinical model and the 2 Ig risk factors was the best in predicting the diagnosis of MCD, with the area under a receiver-operating characteristic curve of 0.91. Conclusions. Combining clinical model and this 2 Ig risk factors provides physicians simple and valuable clinical markers to diagnose MCD.

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First Ukrainian Growth References for Height, Weight, and Body Mass Index for Children and Adolescents Aged 7 to 18 Years

Introduction. To date, growth centiles of children and adolescents have not been created in Ukraine. Therefore, the aim of this study was to construct reference growth charts for height, weight, and body mass index (BMI) of Ukrainian school-aged children and to compare them with World Health Organization references from 2007 for children's BMI. Material and Methods. Among the representative sample of 13,712 students (aged 7 to 18 years) who were included in this study, 6,582 (48%) were boys and 7,130 (52%) were girls. Assessments of height, body mass, and BMI of participants were performed. Reference charts were developed using LMS models within the ChartMaker lms program. Results. We present first growth references for height, weight, and body mass index for Ukrainian children and adolescents aged 7 to 18 years. The younger Ukrainian pediatric population (7-13 years) was heavier than population reported in the multiethnic WHO references, while the older (13-18 years) had lower body weight comparing to the same references from WHO. Conclusions. The constructed reference growth charts are a benchmark for following secular trends in Ukraine and are also an optimal clinical tool for health care. We recommend national implementation of the Ukrainian reference growth charts for anthropometric measurements.

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Serum biochemical reference values of Kyrgyz donkeys ( Equus asinus )

Abstract

The aim of the study was to determine the some serum biochemical values of Kyrgyz donkeys and present the reference values. Fifty (50) healthy donkeys in different ages (6–24 months, 2–15 years, and > 15 years old) and gender (male and female) were clinically examined and blood samples were taken. Serum triglycerides (TG), creatine phosphokinase (CPK), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), total protein (TP), albumin (Alb), creatinine (Creat), urea (Urea), amylase (Amy), lipase (Lip), calcium (Ca), magnesium (Mg), phosphorus (P), cholesterol (Chol), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), glucose (Glu), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and indirect bilirubin (InBil) values were determined. Serum Ca values were found different (P < 0.05) among the age groups (younger, middle aged and older). TBil values were detected different between sex groups (P < 0.01). Serum creat values were determined higher in male donkeys than females (P < 0.01). Serum LDL values were found higher in younger than older donkeys (P < 0.05). It was the first report for donkeys according to LDL values. Serum CPK values were also detected higher in male donkeys and found significantly difference between younger and middle aged donkeys (P < 0.05). Consequently, some serum biochemical values of Kyrgyz donkeys were determined and advised as reference values for Tong region of Kyrgyzstan.

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Curcumin Downregulates Human GM3 Synthase (hST3Gal V) Gene Expression with Autophagy Induction in Human Colon Carcinoma HCT116 Cells

Our recent report showed that curcumin, polyphenolic compound isolated from the herb Curcuma longa, upregulated the gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis with autophagy induction in human lung adenocarcinoma A549 cells. In this study, on the contrary to this finding, we demonstrated that curcumin downregulated the gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 synthesis with autophagy induction in human colon carcinoma HCT116 cells. To clarify the mechanism leading to the downregulation of hST3Gal V gene expression in curcumin-treated HCT116 cells, we analyzed the curcumin-inducible promoter of the hST3Gal V gene by luciferase reporter assays. Promoter deletion analysis demonstrated that the -177 to -83 region, which includes putative binding sites for transcription factors NFY, CREB/ATF, SP1, EGR3, and MZF1, acts as the curcumin-responsive promoter of the hST3Gal V gene. Site-directed mutagenesis and chromatin immunoprecipitation analysis demonstrated that the CREB/ATF binding site at -143 is pivotal for curcumin-induced downregulation of hST3Gal V gene in HCT116 cells. The transcriptional activation of hST3Gal V in HCT116 cells was significantly repressed by an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that AMPK signal pathway mediates hST3Gal V gene expression in HCT116 cells.

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Effect of Osteopathic Visceral Manipulation on Pain, Cervical Range of Motion, and Upper Trapezius Muscle Activity in Patients with Chronic Nonspecific Neck Pain and Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Previous studies have reported that visceral disturbances can lead to increased musculoskeletal tension and pain in structures innervated from the corresponding spinal level through viscerosomatic reflexes. We designed a pilot randomised placebo-controlled study using placebo visceral manipulation as the control to evaluate the effect of osteopathic visceral manipulation (OVM) of the stomach and liver on pain, cervical mobility, and electromyographic activity of the upper trapezius (UT) muscle in individuals with nonspecific neck pain (NS-NP) and functional dyspepsia. Twenty-eight NS-NP patients were randomly assigned into two groups: treated with OVM (OVMG; n = 14) and treated with placebo visceral manipulation (PVMG; n = 14). The effects were evaluated immediately and 7 days after treatment through pain, cervical range, and electromyographic activity of the UT muscle. Significant effects were confirmed immediately after treatment (OVMG and PVMG) for numeric rating scale scores (p 0.05). This study demonstrated that a single visceral mobilisation session for the stomach and liver reduces cervical pain and increases the amplitude of the EMG signal of the UT muscle immediately and 7 days after treatment in patients with nonspecific neck pain and functional dyspepsia.

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