Effect of Vitamin E on Serum Levels of Vascular Endothelial Growth Factor and Angiopoietin-1 in Women with Polycystic Ovary Syndrome: A Pilot Randomized, Placebo-Controlled Trial.

BACKGROUND: Angiogenesis disturbances are common in women with polycystic ovary syndrome (PCOS). Vitamin E has antiangiogenic properties. Data on the effects of vitamin E on angiogenesis in PCOS is limited, so the current study was conducted to evaluate its effects on angiogenic indices in PCOS patients. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was performed on 43 women aged 20-40 years, diagnosed with PCOS (Rotterdam criteria). It was performed at the referral clinic affiliated to Tabriz University of Medical Sciences, Tabriz, Iran, from April 2017 to September 2017. Patients were randomly assigned into two groups to receive either 400 IU/day vitamin E -as alpha tocopheryl acetate- (n=22) or placebo (n=21), for 8 weeks. Anthropometric, and angiogenic parameters including body weight, fat mass and fat free mass, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-1 (Ang-1), and angiopoietin- 2 (Ang-2) were measured by standard methods at the beginning and at the end of study. Statistical Package for Social Science version 25 was used for statistical analysis and P<0.05 were considered significant. RESULTS: After adjusting for potential confounders, we observed that vitamin E supplementation significantly reduced body weight, fat mass, Ang-1, Ang-1/Ang-2 ratio and VEGF (P<0.01). We did not observe any considerable effect for vitamin E on Ang-2 level or bFGF. CONCLUSION: Vitamin E supplementation for 8 weeks in the PCOS women had beneficial effects on body weight, Ang- 1, Ang-1/Ang-2 ratio, and VEGF level (Registration number: IRCT201610193140N18).

High rate of contamination with Staphylococcus aureus in traditional Koozeh cheeses. A molecular typing approach.

BACKGROUND: Koozeh cheese is an Iranian dairy product in rural areas, it is necessary to consider the microbial contamination in this supply. OBJECTIVE: This study evaluates microbial contamination in Koozeh cheese by molecular tools. MAATERIAL AND METHODS: S. aureus and its enterotoxins including type A and type B were identified by biochemical and polymerase chain reaction (PCR) and molecular typing was done by RAPD (Random Amplification of Polymorphic DNA) method. A total of 42 sheeps and cows Koozeh cheese samples were collected from random market in the cities and the surrounding villages. RESULTS: 71.42% of samples were contaminated with Staphylococcus spp. and in 50% of isolates, S. aureus specific coagulase gene "coa" was detected. High-level contamination was observed in 7.14% of samples. The SEA or SEB enterotoxins were produced in 42.84% of isolates. No clonal relationship was observed by molecular approach. CONCLUSION: The obtained results indicate a high level of microbial contamination in Koozeh cheese. Half of isolates were enterotoxin producer and had high diversity and no clonal relationship. Long processing and manipulation are involved in contamination. Improvement in hygiene, training local manufactures of Koozeh cheese, control of products for possible contamination and developing new protocols is needed to decrement of S. aureus contamination in Koozeh Cheese products.

Study on the interaction of anti-inflammatory drugs with human serum albumin using molecular docking, quantitative structure-activity relationship, and fluorescence spectroscopy.

The interaction of 14 anti-inflammatory drugs with human serum albumin (HSA) was investigated using fluorescence quenching, molecular docking studies, and quantitative structure-activity relationship (QSAR) methodology. Binding of anti-inflammatory drugs to HSA plays a fundamental role in their transport, distribution, delivery, and elimination. Binding constants of these drugs to HSA, obtained using the fluorescence quenching method, were within the range 0.01 × 104  M-1 (acetaminophen) to 1881.05 × 104  M-1 (meloxicam). Binding sites and binding constants of these anti-inflammatory drugs were estimated using molecular docking. Inspection of the obtained values for docking score, logKb and Kb , showed that the drugs in this data set have a relatively strong binding constant for HSA. QSAR modelling was applied for binding constants obtained from fluorescence quenching and theoretical molecular descriptors. This modelling led to a linear two-parameter model with a correlation coefficient of 0.95 and adequate robustness. The descriptor results showed the importance of a bonding network and electronegativity as the discriminative structural factors in binding affinity for the HSA molecule.

A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine.

A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box-Behnken experimental design. The response surface methodology based on a three-level, three-variable Box-Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0-8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 µg/cm(2) h) was higher than Tween 80 (1.473 µg/cm(2) h) and lauryl alcohol (0.843 µg/cm(2) h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency.

Development and Validation of a Reversed-Phase High-performance Liquid Chromatography Method for Determination of Desmopressin in Chitosan Nanoparticles.

A simple isocratic reversed-phase high performance liquid chromatographic method was developed for determination of released desmopressin from chitosan nanoparticles in the in vitro media. The chromatographic separation was achieved with acetonitrile/water (25:75, v/v), in which water contained 0.1% v/v trifluoroacetic acid with pH=2.5 as mobile phase, a Chromolith(®) Performance RP-18e column (150×4.6 mm; 5 µm) kept at 40° and ultraviolet detection at 220 nm. The compound was eluted isocritically at a constant flow rate of 1.6 ml/min. The method was validated according to the International Conference on Harmonisation guidelines. The validation characteristics included accuracy, precision, linearity rang, selectivity, limit of detection, limit of quantitation and robustness. The calibration curve was linear (r>0.9999) over the concentration rang 0.5-100 µg/ml. The limit of detection and limit of quantitation in the release media were 0.05 and 0.5 µg/ml, respectively. The proposed method had an accuracy of and intra- and inter-day precision <4.2. Furthermore, to evaluate the performance of the proposed method, it was used in the analysis of desmopressin level in real samples containing chitosan nanoparticles in the in vitro media.

Which parameter is more reliable in a cold hand, NCV or latency.

Temperature affects distal sensory & motor latencies & nerve conduction velocity but not necessarily at the same degree. Purpose of this study is to see which one is affected less and thus could be more reliable in cold conditions. A total of 32 healthy individuals with age range of 18-28 years (mean 22.25 +/- 2.2) participated in this study. Skin Temperature was recorded at wrist. Distal median motor & sensory latencies and transcarpal median NCV were recorded before and after immersion in cold water. Statistical analysis was performed using paired t-test with SPSS. All parameters were affected by cold but the effect was less dramatic in transcarpal NCV. Transcarpal median NCV is least affected parameter by cold, so it may be more reliable than sensory & motor latencies at wrist.

The effects of low level laser in clinical outcome and neurophysiological results of carpal tunnel syndrome.

OBJECTIVES: Carpal tunnel syndrome (CTS) is the most common neuropathy that can be diagnosed with confidence by the nerve conduction study (NCS). One of the recent treatments of CTS is the application of low power laser (LPL) therapy. The present study evaluates the effects of LPL irradiation through NCS and clinical signs and symptoms. METHODS: A total of 80 patients were included in this study. Diagnosis of CTS was based on both clinical examination and electromyographic (EMG) findings. Patients were randomly assigned into two groups. Test group (group A) underwent laser therapy (9-11 joules/cm2) over the carpal tunnel area. Control group (group B) received sham laser therapy. Pain, hand grip strength, median proximal sensory and motor latencies, transcarpal median sensory nerve conduction (SNCV) were recorded. After fifteen sessions of irradiation (five times per week), parameters were recorded again and clinical symptoms were measured in both groups. Pain was evaluated by Visual Analog Scale (VAS; day-night). Hand grip was measured by Jamar dynometer. Paired t-test and independent sample t-test were used for statistical analysis. RESULTS: There was a significant improvement in clinical symptoms and hand grip in group A (p < 0.001). Proximal median sensory latency, distal median motor latency and median sensory latencies were significantly decreased (p < 0.001). Transcarpal median SNCV increased significantly after laser irradiation (p < 0.001). There were no significant changes in group B except changes in clinical symptoms (p < 0.001). CONCLUSIONS: Laser therapy as a new conservative treatment is effective in treating CTS paresthesia and numbness and improves the subjects' power of hand grip and electrophysiological parameters.

Effect of Diethylpyrocarbonate on the Allosteric Properties of Phosphoenolpyruvate Carboxylase from Crassula argentea.

Phosphoenolpyruvate carboxylase from the Crassulacean acid metabolism plant Crassula argentea was substantially desensitized to the effects of regulatory ligands by treatment with diethylpyrocarbonate, a reagent which selectively modifies histidyl residues. Desensitization of the enzyme to the inhibitor malate and the activator glucose 6-phosphate was accompanied by the appearance of a peak in the ultraviolet difference spectrum at 240 nanometers, indicating the formation of ethoxyformylhistidyl derivatives. Hydroxylamine reversed part of the spectral change under native conditions, and almost all of the change under denaturing conditions, but failed to restore sensitivity to effectors. The pH profiles of desensitization to malate and glucose 6-phosphate indicated the involvement of groups on the enzyme with pK, values of 6.8 and 6.4, respectively. Under denaturing conditions, a total of 15 histidine residues per subunit were modified by diethylpyrocarbonate, whereas for the native enzyme nine histidines were modified per subunit. Effector desensitization occurs after the modification of two to three histidyl residues per subunit. The presence of malate reduced the apparent rate constant for desensitization by 60%, suggesting that the modification occurred at the malate binding site. Diethylpyrocarbonate treatment also eliminated the kinetic lag caused by malate. Glucose 6-phosphate did not protect the enzyme against diethylpyrocarbonate-induced desensitization.