Free radical mediated interaction of ascorbic acid and ascorbate/Cu(II) with viral and plasmid DNAs

Previous studies indicate that ascorbic acid, when combined with copper or iron cleaves several viral DNA. ln this study, we generated the ascorbate radical anion electrochemically in a simple chemical environment without the participation of a metal ion. This solution possesses viral DNA scission activity. Ohe absence of catalytic metal ions [Fe (III) and Cu(II)] in the incubation medium was evidenced by metal chelating agents such as desferrioxamine and EDTA. Ohe radical quenching at high EDTA concentration was attributed to ionic strength of EDTA rather than metal chelation. Ohe effects of antioxidants, radical scavangers, catalase, superoxide dismutase and some proteins on DNA cleavage have been tested. Cleavage may not arise directly from ascorbate free radical but the reaction of the radical form of ascorbate with oxygen may produce the actual reactive species. Aerobic oxidation of ascorbate itself strictly requires transition metal catalysts, however electrochemically produced ascorbyl radical avoided the kinetic barrier that prevented direct oxidation of ascorbic acid with oxygen and eliminated the need for the transition metal ion catalysts.     

Plasmid profile typing provides a method for the differentiation of strains of Salmonella enteritidis phage type 4 isolated in Turkey

Five phage types have been identified in 38 strains of Salmonella enteritidis isolated in Turkey in the 20-month period June 1992-January 1994. Strains belonging to phage type 4 predominated. Within phage type 4, plasmid profile typing has proved a useful method of strain discrimination and has confirmed the identity of a putative outbreak involving canteen workers in an industrial complex.     

A Phase 2a randomized,single-center,double-blind,placebo-controlled study to evaluate the safety and preliminary efficacy of oral iOWH032 against cholera diarrhea in a controlled human infection model

Cholera remains a major cause of infectious diarrhea globally. Despite the increased availability of cholera vaccines, there is still an urgent need for other effective interventions to reduce morbidity and mortality. Furthermore, increased prevalence of antibiotic-resistant Vibrio cholerae threatens the use of many drugs commonly used to treat cholera. We developed iOWH032, a synthetic small molecule inhibitor of the cystic fibrosis transmembrane conductance regulator chloride channel, as an antisecretory, host-directed therapeutic for cholera. In the study reported here, we tested iOWH032 in a Phase 2a cholera controlled human infection model. Forty-seven subjects were experimentally infected with V. cholerae El Tor Inaba strain N16961 in an inpatient setting and randomized to receive 500 mg iOWH032 or placebo by mouth every 8 hours for 3 days to determine the safety and efficacy of the compound as a potential treatment for cholera. We found that iOWH032 was generally safe and achieved a mean (± standard deviation) plasma level of 4,270 ng/mL (±2,170) after 3 days of oral dosing. However, the median (95% confidence interval) diarrheal stool output rate for the iOWH032 group was 25.4 mL/hour (8.9, 58.3), compared to 32.6 mL/hour (15.8, 48.2) for the placebo group, a reduction of 23%, which was not statistically significant. There was also no significant decrease in diarrhea severity and number or frequency of stools associated with iOWH032 treatment. We conclude that iOWH032 does not merit future development for treatment of cholera and offer lessons learned for others developing antisecretory therapeutic candidates that seek to demonstrate proof of principle in a cholera controlled human infection model study.Trial registration: This study is registered with ClinicalTrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT04150250","term_id":"NCT04150250"}}NCT04150250.     

NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans

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Efficacy of Ankaferd Blood Stopper on bone healing in diabetic rats: a stereological and histopathological study

We evaluated the effects of Ankaferd Blood Stopper (ABS) and routine antibiotic prophylaxis (AP) on early healing of bone defects in diabetic rats. We used 48 rats in the study. Diabetes was induced in 24 rats using streptozotocin; the remaining 24 healthy untreated rats served as controls. Twelve of the diabetic rats and 12 of the healthy rats were treated with AP for 3 days before surgery. Bilateral bone defects were created in the mandible of all animals. ABS was applied to the defects on the left sides of the mandibles, while nothing was applied to the right sides. Animals were sacrificed on days 7 and 14 after operation and examined for histopathology and by stereology. The volume of newly formed bone was significantly less in the diabetic rats on both days 7 and 14. Local administration of ABS significantly increased the mean volume of newly formed bone in both diabetic and nondiabetic rats at days 7 and 14. No significant difference in new bone formation was found between AP and ABS treatment in diabetic rats. Both AP and local administration of ABS have beneficial effects on bone healing in diabetic animals.     

Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance

BACKGROUND/AIMS: Insulin resistance is associated with serum C-reactive protein (CRP) levels. We aimed to evaluate the effect of bicalutamide on insulin resistance and serum CRP levels in non-obese polycystic ovarian syndrome (PCOS) patients. METHODS: 40 non-obese patients (BMI < or =25 kg/m2) with PCOS and, 40 age- and BMI-matched healthy women were studied. Patients received bicalutamide orally at the dose of 25 mg/day. Serum CRP levels were measured with immunometric assay. Homeostasis model assessment (HOMA-IR) index was used for insulin resistance. RESULTS: Mean Ferriman-Gallwey score (FGS) (p = 0.001), insulin (p = 0.001), serum glucose (p = 0.001), prolactin (p < 0.003), total (p < 0.04) and free testosterone (p = 0.001) and free androgen index (FAI) levels (p = 0.001) of PCOS subjects were higher than in the control group. Mean HOMA-IR of PCOS patients was higher than in control subjects (2.43 +/- 1.2 and 0.94 +/- 0.37, p = 0.001). CRP levels in subjects with PCOS was also higher than in control subjects (4.27 +/- 1.33 and 0.98 +/- 0.19, p = 0.001). After bicalutamide treatment, FGS, free and total testosterone and FAI decreased (p = 0.001). HOMA-IR, prolactin and CRP levels did not show any statistical difference with bicalutamide treatment. CONCLUSIONS: PCOS patients had insulin resistance and a high CRP level. Bicalutamide treatment did not influence insulin resistance and CRP level in PCOS, and this ineffectiveness of bicalutamide on CRP levels may be the result of insulin resistance and/or high prolactin levels at this time.     

IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1

In myasthenia gravis (MG), TNF and IL-1beta polymorphisms and high serum levels of these proinflammatory cytokines have been observed. Likewise, TNF and IL-1beta are critical for the activation of acetylcholine receptor (AChR)-specific T and B cells and for the development of experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. We tested the therapeutic effect of human recombinant IL-1 receptor antagonist (IL-1ra) in C57BL/6 mice with EAMG. Multiple daily injections of 0.01 mg of IL-1ra administered for 2 wk following two AChR immunizations decreased the incidence and severity of clinical EAMG. Furthermore, IL-1ra treatment of mice with ongoing clinical EAMG reduced the clinical symptoms of disease. The IL-1ra-mediated suppression of clinical disease was associated with suppressed serum IFN-gamma, TNF-alpha, IL-1beta, IL-2, IL-6, C3, and anti-AChR IgG1 without influencing total serum IgG. Therefore, IL-1ra could be used as a nonsteroidal drug for the treatment of MG.     

Plasma values of oxidants and antioxidants in acute brain hemorrhage

The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.     

The effects of chronic aerobic and anaerobic exercises n lymphocyte subgroups

Exercise is the strongest stress to which the body is ever exposed. The body responds to this stress through a set of physiological changes in its metabolic, hormonal and immunological systems. In this study, responses of the immune system to the long-term aerobic and anaerobic exercises have been investigated. Twenty-four sedentary male university students and officers participated in this study. Subjects were divided into two groups, each consisting of twelve people. Group-1 (age: 25.67 +/- 3.79 years, height: 174.83 +/- 5.15 cm, body mass: 72.17 +/- 8.05 kg) and Group-2 (age: 24.83 +/- 2.89 years, height: 175.3 +/- 6.68 cm, body mass: 70.67 +/- 6.15 kg). After physical examinations of the two groups, resting ECG, respiratory function tests and metabolic tests with the use of the breath by breath method were completed, and anerobic heart rates at the threshold level were determined. The first group was subjected to exercise using Monark ergometry cycles at a heart rate 10% below the threshold level for 8 weeks, 3 days a week, 30 min a day. The second group exercised at a heart rate 10% above the threshold level for 8 weeks, 3 days a week, 20 min a day. Heart rates were checked with the Polar Test during exercises. Pre-exercise (Ep) venous blood samples were taken from each group before their 1st and 24th exercises. Hb (gr), Hct (%), erythrocyte (x10(6)/microl), leukocyte (x10(6)/microl), leukocyte subpopulations (neutrophil, lymphocyte, monocyte, eosinophil, basophil %) and thrombocyte (x10(6)/microl) values were determined. CD3, CD4, CD8, CD19 and CD56 values were determined by Flow Cytometry method using monoclonal antibodies. The chronic effects of exercise were examined through a comparison of Ep blood samples at the 1st exercise with Ep blood samples at the 24th exercise. While the increase in the total leukocyte number was significant (p<0.05) in the first group, increase in the second group was found to be non-significant. When percentiles of leukocyte subpopulations were taken into consideration, changes in the first and second group were found to be non-significant. When lymphocyte subgroups were examined; in the first group a decrease in CD3 and CD4 percentiles to 7% and 12%, respectively (p<0.05) and a 65% increase (p<0.01) in the CD56 value were observed. In the second group a decrease in CD3 and CD4 percentiles to 13% and 17%, respectively (p<0.05) and a 73% increase (p<0.01) in the CD56 value were observed. The Sample-t Test and The Wilcoxon Test were used for statistical analysis.