Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice

Abstract

Context: Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.

Objective: The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.

Material and methods: SM was administered orally (5, 10, 20, 50, 100, and 200?mg/kg; p.o.) 60?min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, l-NAME (10?mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50?mg/kg, i.p.), were administered separately 30?min before SM (20 and 100?mg/kg).

Results: SM at its effective doses 10, 20, 50, and 100?mg/kg decreased the immobility time in a dose-dependent manner (p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.001, respectively) in FST. SM (10, 20, 50, and 100?mg/kg) also lowered the immobility measure dose dependently in TST (p?<?0.01, p?<?0.05, p?<?0.01, and p?<?0.001, respectively). In addition, 50% of maximum response (ED₅₀) of SM was around 10?mg/kg. The dose 100?mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, l-NAME reversed the effect of SM (20 and 100?mg/kg) in FST and SM (100?mg/kg) in TST. However, AG did not influence this impact.

Conclusion: The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.     

Knowledge of and interest in opioid overdose education and naloxone distribution among US veterans on chronic opioids for addiction or pain

Aims: The Veterans Health Administration (VHA) is implementing opioid overdose (OOD) education and naloxone distribution to reduce rising rates of OOD deaths. This study assessed knowledge and interest in OOD prevention with naloxone at a VHA hospital where naloxone kits were not yet available. Methods: Veterans receiving opioids for ≥3 months, including 52 from the Opioid Substitution Clinic (OSC) and 38 from the Pain Management Clinic (PMC), were interviewed about their attitudes and experience with OOD and naloxone. Findings: 52% of OSC and 21% of PMC veterans reported having ever experienced an OOD. Less than half had heard of naloxone and none owned a naloxone kit. After a brief explanation, 73% of OSC and 55% of PMC veterans reported wanting a kit. Veterans who reported wanting a kit were more likely to have witnessed (p?<?0.001) and/or experienced (p?<?0.001) an OOD and were more likely to have used intravenous drugs in their lifetimes (p?<?0.05). Conclusions: Participants were not well informed about naloxone but many OSC veterans had a history of OOD and were interested in having a naloxone kit. There was also a subgroup of veterans prescribed opioids for chronic pain who had a history of OOD and were interested in naloxone.     

Prooxidant-antioxidant balance in Iranian veterans exposed to mustard gas and its correlation with biochemical and hematological parameters

The present study aimed to evaluate serum prooxidant -antioxidant balance (PAB) in an Iranian population exposed to sulfur mustard (SM) more than 20 years ago. In this study, 42 SM-exposed subjects and 30 unexposed subjects (as controls) were recruited. Serum PAB, biochemical, and hematological parameters were measured in all subjects. Correlation of PAB with biochemical and hematological parameters was determined. The mean PAB values in the SM-exposed group (82.5?±?34.8 HK) were significantly higher than that in the control group [47.5?±?17.8 HK] (p?<?0.001). The results demonstrated that serum PAB values were positively correlated with alkaline phosphatase activities in the SM-exposed group. Furthermore, PAB values showed a significant negative correlation with hepatic enzymes (AST, ALT), triglycerides, total bilirubin, and mean corpuscular hemoglobin concentrations. PAB values showed a borderline significant negative correlation with uric acid. The present results suggest that late oxidative stress and alterations in biochemical and hematological parameters may be a consequence of the frequent respiratory infections rather than direct toxic effects of SM.     

Tear total protein analysis in patients with late sulfur mustard-induced ocular complications: a cross-sectional study

Background: Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15–20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients.

Methods: Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA.

Results: Total protein concentration was significantly lower in tears of the SM compared to control group (p?<?0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group (p?<?0.01). Tear CGRP concentration was found to be lower in the SM vs. control group (p?<?0.05) but no significant difference in CGRP/total protein was observed (p?>?0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups (p?>?0.05).

Conclusion: The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications.     

The effect of vitamin E on tracheal responsiveness and lung inflammation in sulfur mustard exposed guinea pigs

Pulmonary complications of sulfur mustard (SM) range from mild respiratory symptoms to even severe bronchial stenosis. In the present study, the protective effect of vitamin E on tracheal responsiveness (TR) and lung inflammation of SM-exposed guinea pigs were examined. Guinea pigs were exposed to ethanol (control group), 40?mg/m³ inhaled SM and ethanol vehicle (sulfur mustard exposed (SME) group), SME treated with vitamin E (SME + E), SME with dexamethasone (SME + D) and both drugs (SME + E + D), (n?=?8 for each group). TR to methacholine, total and differential white blood cell (WBC) count of lung lavage and serum cytokines were evaluated 14 days post-exposure. TR, WBC, interleukin 4 (IL-4), interferon gamma (INF-γ), eosinophil, and monocyte levels in SME guinea pigs were significantly higher, but lymphocyte was lower than those of controls (P?<?0.05 to P?<?0.001). TR, IL-4, and eosinophil levels in SME + E, SME + D and SME + E + D, INF-γ in SME + E and SME + E + D and WBC in SME + E were significantly decreased compared to that of the SME group (P?<?0.01 to P?<?0.001). In addition, the TR of SME + D + E was significantly higher than that of SME + E (P?<?0.01) and SME + D (P?<?0.05) groups. The results showed a preventive effect of vitamin E, dexamethasone and their combination on TR and lung inflammation in SME guinea pigs.     

Cytogenetic and hematological alterations induced by acute oral exposure of imidacloprid in female mice

Imidacloprid (IMD), 1(6-chloro-3-pyridinyl)methyl)-N-nitro-2-imidazolidinimine, was administered in female mice to study in vivo cytogenetic (chromosomal aberrations (CAs) and micronucleus assay) and hematological effects. The acute oral LD₅₀ was determined to be 150?mg/kg bw in mice following OECD guidelines using AOT StatPgm425 software. The mice were administered orally with distilled water (negative control); mitomycin C (MMC), 1?mg/kg (positive control) and sub-lethal doses of 37.5 (low), 75.0 (medium) and 112.5 (high) mg/kg bw (25%, 50% and 75% of LD₅₀) of IMD to analyze CAs and hematological effects after 24?h, whereas micronucleus test (MT) after 48?h. The genotoxicity analysis revealed that selected test doses of IMD – medium and high doses – induced significantly mitotic inhibition (p?<?0.01), CAs (p?<?0.01) and at high dose micronucleus (MN) formation (p?<?0.05). Significant changes in red blood cell (RBC; p?<?0.01), hemoglobin (Hb; p?<?0.01) and erythrocyte sedimentation rate (ESR; p?<?0.001) were observed, except WBC in which significant increase (p?<?0.001) was observed. Present observation substantiates overall significant dose dependent genotoxic potential (p?<?0.05; r?=?0.98) of IMD. Precautions should be taken to minimize possible risk to exposed farmers of the state of Haryana (India) – an agrarian economy.     

Efficacy of Aloe vera/olive oil cream versus betamethasone cream for chronic skin lesions following sulfur mustard exposure: a randomized double-blind clinical trial

Background: Chronic pruritic skin lesions are among the common late complications of sulfur mustard intoxication. In the present randomized double-blind clinical trial, therapeutic efficacy of Aloe vera/olive oil combination cream in the alleviation of these lesions was evaluated and compared to that of betamethasone 0.1% cream.

Methods: Sixty-seven Iranian chemical warfare-injured veterans were randomized to apply A. vera/olive oil (n?=?34, completers?=?31) or betamethasone 0.1% (n?=?33, completers?=?32) cream twice daily for 6 weeks. Evaluation of pruritus severity was performed using a pruritic score questionnaire and visual analogue scale (VAS).

Results: Both treatments were associated with significant reductions in the frequency of pruritus (p?<?0.05), burning sensation (p?<?0.01 and p?<?0.001 in A. vera/olive oil and betamethasone group, respectively), scaling (p?<?0.01 and p?<?0.05) and dry skin (p?<?0.001) at the end of trial. Fissure and excoriation were only reduced in the A. vera group (p?<?0.05). The change in the frequency of hyper- and hypopigmentation lesions, blisters, erythema and lichenification did not reach statistical significance in any of the groups (p?>?0.05). Mean pruritus (p?<?0.05) and VAS scores (p?<?0.01 and p?<?0.05) were significantly decreased by the end of trial in both groups. The rate of improvement in the pruritus severity [defined as being classified in a less severe category (mild, moderate and severe)] was found to be comparable between the groups (p?>?0.05).

Conclusion: A. vera/olive oil cream was at least as effective as betamethasone 0.1% in the treatment of sulfur mustard-induced chronic skin complications and might serve as a promising therapeutic option for the alleviation of symptoms in mustard gas-exposed patients.     

Chronic diclofenac (DCF) exposure alters both enzymatic and haematological profile of African catfish,Clarias gariepinus

Pharmaceuticals are used extensively in human and veterinary medicine to eradicate or prevent diseases. The residues of these drugs have been detected in aquatic ecosystem; nevertheless, their toxicological effects on Clarias gariepinus have not been critically investigated. In this study, the toxic effects of diclofenac (DCF), a non-steroid anti-inflammatory drug, were studied in C. gariepinus by acute and chronic static renewable bioassay. The 96?h LC₅₀ of DCF to C. gariepinus was 25.12?mg/L. Exposure to acute toxicity resulted in abnormal behavior and mortality of some fish. Compared with the control, chronic exposure of the fish to concentration (1.57, 3.14 and 6.28?mg/L) showed significantly higher mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and white blood cell (WBC), with significantly lower haemoglobin (Hb), haematocrit, red blood cell (RBC) and mean corpuscular haemoglobin (MCH) with increase in the concentration of the drug. Furthermore, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and glucose values significantly increased while protein levels were reduced (p?相似文献   

Methyl-thiophanate increases reactive oxygen species production and induces genotoxicity in rat peripheral blood

Methylthiophanate is one of the widely used fungicides to control important fungal diseases of crops. The aim of this study was to elucidate the short-term hematoxicity and genotoxicity effects of methylthiophanate administered by intraperitoneal way at three doses (300, 500 and 700?mg/kg of body weight) after 24, 48 and 72?h. Our results showed, 24?h after methylthiophanate injection, a hematological perturbation such as red blood cells (p?<?0.05, p?<?0.05 and p?<?0.01) and hemoglobin content (p?<?0.05), respectively, and a noticeable genotoxic effect in WBC evidenced by a significant increase in the frequency of the micronuclei and a decrease in cell viability. An increase in erythrocyte osmotic fragility was also noted after 24 and 48?h of methylthiophanate treatment at graded doses. A significant increase in hydrogen peroxide, advanced oxidation of protein products and malondialdehyde levels, in erythrocytes of methylthiophanate-treated rats with 300, 500 and 700?mg/kg of body weight, was also observed after 24?h of treatment (p?<?0.05, p?<?0.01 and p?<?0.001, respectively), suggesting the implication of oxidative stress in its toxicity. Antioxidants activities of superoxide dismutase and glutathione peroxidase in erythrocytes significantly increased (p?<?0.001) 24?h after the highest dose injected. While all these parameters were improved after 72?h of methylthiophanate injection (300, 500 and 700?mg/kg body weight). In conclusion, these data showed that the exposure of adult rats to methylthiophanate resulted in oxidative stress leading to hematotoxicity and the impairment of defence system, confirming the pro-oxidant and genotoxic effects of this fungicide.     

Can monocyte/HDL show inflammatory activity of isotretinoin treatment in acne patients?

Abstract

Aim: There are reports that isotretinoin causes some important diseases such as teratogenicity, inflammatory bowel disease and sacroiliitis by triggering inflammation. (Monocyte/HDL (high density lipoprotein) ratio) MHR is closely related to inflammation and is thought to be an indicator of atherosclerotic development. We aimed to investigate how isotretinoin (ISO) affects the immunoinflammatory response in acne patients.

Materials and Methods: In this study, 116 nodulocystic acne patients who received ISO treatment for at least three months were evaluated retrospectively. ISO treatment was given to patients at a dose of 0.5–1?mg/kg. Pre-treatment and post-treatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, mean platelet volume (MPV), platelet, plateletcrit, platelet distribution width (PDW), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), total cholesterol, LDL cholesterol, triglyceride, HDL cholesterol and MHR were evaluated.

Results: MPV and MHR values were significantly increased after 3?month treatment (p?<?0.05). There was no significant change in NLR and PLR values (p?>?0.05). There was a significant decrease in neutrophil count (p?<?0.05). There were no significant changes in WBC, lymphocyte, monocyte, platelet, plateletcrit values (p?>?0.05). Total cholesterol, LDL cholesterol and triglyceride levels were significantly increased after three months of treatment (p?<?0.05). HDL cholesterol levels decreased significantly after three months of treatment (p?<?0.05).

Conclusion: We concluded that ISO treatment may trigger inflammation due to the increase in MPV and MHR value. MHR can show inflammation after ISO treatment.     

Riboflavin attenuates lipopolysaccharide-induced lung injury in rats

Abstract

Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20?μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p?<?0.01) and MPO activity (p?<?0.001), whereas marked decrease in glutathione (GSH) content (p?<?0.001), glutathione reductase (GR) (p?<?0.001) and glutathione peroxidase (p?<?0.01) activity. These changes were significantly (p?<?0.001) improved by treatment with riboflavin in a dose-dependent manner (30 and 100?mg/kg, respectively). Riboflavin (100?mg/kg, p.o.) showed similar protective effects as dexamethasone (1?mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p?<?0.001) and levels of CAT mRNA expression was decreased significantly (p?<?0.001) in the animals exposed to LPS, while treatment with riboflavin significantly (p?<?0.01) improved expression of both gene. In conclusion, the present study clearly demonstrated that riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.     

Association between cigarette consumption and academic achievement in Korean adolescents

Aims: The purpose of this study was to examine whether smoking frequency and cigarette consumption are related to academic achievement in Korean adolescents. Method: Data from the Seventh Korea Youth Risk Behavior Web-based Survey (KYRBWS-VII) administered in 2011 were analyzed; 75,643 adolescents from the first year of middle school through the third year of high school participated in the survey. We used multivariate logistic regression analysis to investigate the association in question after adjusting for variables such as age, body mass index, frequency of drinking, frequency of breakfast consumption, parents’ education level, family economic status, mental stress and the frequency of vigorous physical activity (PA), moderate PA and muscular strength exercises. Results: The odds ratios (ORs) for achieving average or higher academic achievement in boys compared with those who never smoked and stratified by the frequency of smoking were as follows: 1–2 day(s) per month, 0.594 (p?<?0.001); 3–5 days per month, 0.571 (p?<?0.001); 6–9 days per month, 0.529 (p?<?0.001); 10–19 days per month, 0.472 (p?<?0.001); 20–29 days per month, 0.491 (p?<?0.001) and every day, 0.342 (p?<?0.001). For girls, the ORs for achieving average or higher academic achievement compared with those who never smoked and stratified by the frequency of smoking were as follows: 1–2 day(s) per month, 0.482 (p?<?0.001); 3–5 days per month, 0.409 (p?<?0.001); 6–9 days per month, 0.648 (p?=?0.037); 10–19 days per month, 0.723 (p?=?0.032); 20–29 days per month, 0.543 (p?<?0.001) and every day, 0.433 (p?<?0.001). The ORs in boys for achieving average or higher academic achievement compared with those who never smoked and stratified by cigarette consumption were as follows: <1 cigarette per day, 0.656 (p?<?0.001); 1 cigarette per day, 0.541 (p?<?0.001); 2–5 cigarettes per day, 0.446 (p?<?0.001); 6–9 cigarettes per day, 0.375 (p?<?0.001); 10–19 cigarettes per day, 0.281 (p?<?0.001) and ≥20 cigarettes per day, 0.340 (p?<?0.001). For girls, the ORs for achieving average or higher academic achievement compared with those who never smoked and stratified by cigarette consumption were as follows: <1 cigarette per day, 0.550 (p?<?0.001); 1 cigarette per day, 0.507 (p?<?0.001); 2–5 cigarettes per day, 0.549 (p?<?0.001); 6–9 cigarettes per day, 0.356 (p?<?0.001); 10–19 cigarettes per day, 0.353 (p?<?0.001) and ≥20 cigarettes per day, 0.729 (p?=?0.242). Conclusion: There are certain indicators that smoking negatively influences educational achievement in Korean adolescents. To improve academic achievement, it is recommended that adolescents do not smoke.     

Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations

Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept “chemotherapy at home.” In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich’s Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size ～40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI-NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH (p?<?0.001), CK-MB (p?<?0.001), AST (p?<?0.001), ALT (p?<?0.001) and MDA levels (p?<?0.001) and reduction in SOD (p?<?0.001) and CAT levels (p?<?0.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site.     

Internet addiction of adolescents in China: Prevalence,predictors, and association with well-being

Internet addiction is a mental health problem that affects a significant number of people worldwide. Our study attempted to investigate the prevalence of Internet addiction among Chinese adolescents and to explore the predictors of Internet addiction and its association with well-being. A total of 10,988 adolescents from nine different cities in China were surveyed using the Diagnostic Questionnaire (DQ) for Internet addiction, the Center for Epidemiologic Studies Depression Scale, the Rosenberg Self-esteem Scale, and the Adolescent's Satisfaction with Life Scale. The mean age of the whole sample was 17.2 years (ranging from 13 to 23 years). The prevalence rate of Internet addiction among the surveyed adolescents was 7.5%, which was influenced by gender and grade (χ²?=?74.027, p?<?0.001; χ²?=?7.162, p?<?0.05). The breadth of extracurricular activities, the age when people used Internet for the first time, and whether people used Internet for the first time in Internet bar were significant predictors of Internet addiction (β?=??0.065, p?<?0.001; β?=??0.101, p?<?0.001; β?=?0.545, p?<?0.001). Finally, our study found evidence demonstrating the link between Internet addiction and well-being. Increased symptoms of problematic use were associated with decreased self-esteem (F?=?258.344, p?<?0.001), satisfaction with life (F?=?232.428, p?<?0.001), and increased depression (F?=?607.062, p?<?0.001).     

Risk factors for venous symptoms in Russian patients with chronic venous disease

Objectives: The study aimed to investigate risk factors for venous symptoms in Russian patients with chronic venous disease (CVD).

Methods: Data on 487 patients with CVD aged 18?years and more were extracted from the database of a cross-sectional population-based study on the prevalence of CVD in a rural settlement. Risk factors for venous symptoms were calculated by multiple regression analysis. The study is registered at clinicaltrials.gov as NCT03900234, 1 April 2019.

Results: A total of 259 patients (53.2%) had venous symptoms. Female gender, hard labour (HRs 1.8 and 1.4, p?<?.01), age, family history of CVD and being employed (HRs 1.009, 1.3, 1.27, p?<?.05) are risk factors for development of symptoms. After calculating for different complaints separately, female gender was confirmed as a risk factor for all symptoms. Family history of CVD with HR 1.4 is a risk factor for heaviness (p?<?.01) and fatigue (p?<?0.05). Employment predicts heaviness, sensation of swelling and night cramps – HRs 1.38, 1.7 and 1.9 respectively (p?<?.05). Hard labour is a risk factor for sensation of swelling with HR 2.1 (p?<?.05), pain and night cramps (HRs 2.2 and 4.4, p?<?.01). Prolonged standing is associated with sensation of swelling – HR 1.05 (p?<?.05). Superficial venous reflux is a predictor only for venous pain (HR 2.4, p?<?.01).

Conclusions: This study presents independent risk factors for venous symptoms in CVD patients. It demonstrates that different symptoms are associated with different factors.     

Recalculation of cardiovascular risk score as a surrogate marker of change in clinical care of diabetes patients: the Alphabet POEM project (Practice Of Evidence-based Medicine)

SUMMARY

Aims: To assess the impact of evidence-based strategies on the care of subjects with diabetes, in particular on their coronary heart disease (CHD) risk, using the Alphabet Strategy template and coronary heart disease (CHD) risk calculators as novel audit tools.

Methods: Diabetes and cardiovascular parameters were collected on 400 consecutive type 2 diabetes patients attending the outpatient clinic. The subjects were men and women aged 21-75 years with necessary follow-up data from referral or first chronological available letter in the notes (T0) to the most recent follow-up visit (Tfu). The average follow-up period was 5 years. Absolute CHD risk was calculated using the Framingham risk function and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The results were analysed using Student's paired t-test and chi-squared test.

Results (T0 vs.Tfu): Advice: smoking status improved 18.3 vs. 15.5%: p?=?0.3. Blood pressure: systolic blood pressure improved 145.8?±?21.1 vs. 140.1?±?20.5mmHg: p?<?0.0001. Diastolic blood pressure improved 82.0?±?12.2 vs. 76.5?±?11.0mmHg: p?<?0.0001. Cholesterol: total cholesterol improved 5.8?±?1.6 vs. 4.9?±?1.0 mmol/L: p?<?0.0001; high density lipoprotein (HDL) cholesterol improved 1.05 vs. 1.26 mmol/L: p?<?0.001. Diabetes control: glycated haemoglobin (HbA1c)% worsened 7.9?±?1.8 vs. 8.1?±?1.5: p?<?0.0001. However, when adjusted for duration of diabetes, this improved non-significantly by 12% overall. Eye examination: improved 86.5 vs. 97.5%: p?<?0.001. Feet examination: improved 69.8 vs. 83.5%: p?<?0.001. Guardian drugs: significantly more patients were on aspirin (29.0 vs. 83.5%: p?<?0.001), angiotensin converting enzyme (ACE) inhibitors (32.0 vs. 64.5%: p?<?0.001), and lipid lowering therapy (16.8 vs. 55.0%: p?<?0.001). Heart disease risk scores: a significant reduction in Framingham 10-year absolute cardiac risk was achieved (20.6?±?10.04% vs. 16.7?±?9.1%: p?=?0.001). Using the UKPDS risk engine, there was a non-significant reduction in absolute CHD risk over the follow-up period (23.8?±?14.8% vs. 23.7?±?15.5: p?=?NS). There were significant improvements between age-adjusted risk score (Tadj) and follow-up values (Tfu) (Framingham: 23.67% (Tadj) vs. 16.7% (Tfu); UKPDS 31.2% (Tadj) vs. 23.7% (Tfu)). For UKPDS stroke risk, a significant improvement was seen from Tadj to Tfu (19.0% (Tadj) vs. 16.4% (Tfu): p?<?0.001), with a significant deterioration noted between T0 and Tfu (11.5% (T0) vs. 16.4% (Tfu): p?<?0.0001).

Conclusions:The Alphabet Strategy is a novel evidence-based approach to clinical diabetes care, which produced a statistically significant improvement in most of the assessed parameters. The Alphabet Practice Of Evidence-based Medicine (POEM) template is a useful clinical tool for diabetes care and audit. It includes most of the components of diabetes audit required by the National Service Framework (NSF) and the United Kingdom GP contract.     

Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers

Abstract

Context: Acetaminophen (APAP) leads to severe hepatic and renal necrosis and thus causes significant clinical problems. Artemisia pallens Walls ex D.C. (Asteraceae) possesses various pharmacological properties such as antidiabetic, antioxidant, analgesic, and anti-inflammatory activity.

Objective: The objective was to evaluate the protective effects of Artemisia pallens methanol extract (APME) in APAP-induced hepatic and nephro-toxicity.

Materials and methods: The methanolic extract of aerial parts of Artemisia pallens (APME) was prepared. Toxicity was induced in male Wistar rats (180–220?g) by administration of APAP (700?mg/kg, p.o., 14?d). APME (100, 200, and 400?mg/kg, p.o.) was administered to rats 2?h before APAP oral administration. Various biochemical and molecular parameters along with histopathological aberration were studied in the kidney and liver of rats.

Results: Pretreatment with APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) decreased aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, blood urea nitrogen (BUN), and serum creatinine as compared with APAP-treated rat. Decreased level of serum albumin, serum uric acid, and HDL were significantly (p?<?0.01 and p?<?0.001) restored by APME (200 and 400?mg/kg, p.o.) pre-treatment. Administration of APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) reduced the elevated level of cholesterol, LDL, LDH, triglyceride, and VLDL. It also significantly (p?<?0.01 and p?<?0.001) restored the altered level of hepatic and renal antioxidant enzymes (superoxide dismutase (SOD) and glutathione (GSH)). The increased level of malondialdehyde (MDA) and nitric oxide (NO) in hepatic as well as renal tissue was significantly (p?<?0.01 and p?<?0.001) decreased by APME (200 and 400?mg/kg, p.o.) administration. Histological alternation induced by APAP in liver and kidney was also reduced by the APME (200 and 400?mg/kg, p.o.) pre-treatment.

Conclusion: It is concluded that the methanol extract of Artemisia pallens alleviates APAP induced in rats toxicity through its antioxidative and anti-inflammatory actions.     

Haematological Changes in the Garden Lizard,Calotes Nemoricola due to the Defensive Secretion of the Grasshopper,Poecilocerus Pictus

ABSTRACT

Defensive secretion of the Grasshopper, Poecilocerus pictus produced significant changes in the blood components of the predator lizard, C. nemoricola. The red blood cell (RBC) count, haemoglobin (Hb) concentration, packed cell volume (PCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and white blood cell (WBC) count decreased greatly, whereas mean corpuscular volume (MCV) showed significant increase following the administration of lethal dose of defensive secretion. These changes however were found to be reversible toward control levels in the lizards injected with sublethal dose. Disrupted erythropoeitic activity in lizards by the cardenolides in the defensive secretion was suggested.     

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.

Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory.

Materials and methods Rats were pretreated with metformin (200?mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured.

Results Pretreatment with metformin (met) in the met?+?ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p?<?0.001) and increased latency time compared with the I/R group (p?<?0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R?+?met group (p?<?0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p?<?0.001) but increased that compared with the sham group (p?<?0.001). The level of pro-BDNF decreased in the met?+?CC?+?I/R group compared with the met?+?I/R group (p?<?0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p?<?0.001).

Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.