The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats

Objective

This study was performed to evaluate the effect of pregabalin co-administration with vitamin E in Partial Sciatic Nerve Ligation (PSNL)-induced neuropathic pain in rats.

Methods

Male Wistar rats were randomly allocated as control, sham, and PSNL groups (n = 8). PSNL was induced by tight ligation of the sciatic nerve with a copper wire. On day 14th, the PSNL and sham operated rats received either pregabalin (1, 3, and 30 mg/kg), vitamin E (100 and 200 mg/kg), or their combination intraperitoneally. An antinociceptive effect was evaluated as latency times and Maximum possible Effect Percent (%MPE) using tail-flick test. Locomotor activity was evaluated by open-field test before PSNL surgery and then twice at the 14th days (before and after drug injection). Ligated nerves were removed on the 28th days after surgery for histological examinations.

Results

The time course of latency times and %MPE showed significant decrease in PSNL but not in sham and control groups. Pregabalin (3 and 30 mg/kg) and vitamin E (100 and 200 mg/kg) caused significant increases in latency time in PSNL (but not sham) group compared to control group. Vitamin E 200 mg/kg increased significantly %MPE in PSNL group compared to sham group. In addition, the %MPE following combination treatment of pregabalin (30 mg/kg) and vitamin E (100 mg/kg) was significantly higher than both vitamin E and control group. Also combination of pregabalin with 100 mg/kg of vitamin E reversed Wallerian degeneration of sciatic nerve and the inflammatory responses to almost similar to sham group. Pregabalin and vitamin E did not affect locomotor activity.

Conclusion

Our results showed antinociceptive effects of both vitamin E and pregabalin alone or in combination in PSNL rats and also neuroprotective properties without affecting locomotor activity.

     

A comprehensive insight into potential roles of Nigella sativa on diseases by targeting AMP-activated protein kinase: a review

ObjectivesNigella sativa (NS) is a known medicinal herb with numerous therapeutic effects such as antidiabetic, anti-proliferative, anti-inflammatory, and anti-cancer activities. It has been indicated that NS can regulate cellular metabolism by adjusting transduction signaling pathways. Adenosine monophosphate-activated protein kinase (AMPK) is one of the main physiological processes, such as energy hemostasis, cellular metabolism, and autophagy regulators. Herb-derived medicines have always been considered as one of the main AMPK activators, and surprisingly recent data has demonstrated that it can be a target for NS and its derivatives.Evidence acquisitionThe literature search was conducted in PubMed, SCOPUS, Embase, ProQuest, and Google Scholar electronic resources. Published articles up to September 2020 were considered, and those of which investigated Nigella sativa effects on the AMPK pathway after meeting the inclusion criteria were included.ResultsThe search was performed on several online databases such as PubMed, Scopus, Embase, ProQuest, and Google Scholar from inception until January 2020. Among the initial search, 245 studies were found. After removing duplicated data and meeting the inclusion criteria, only 14 studies were selected. They included the effects of NS and its bioactive compounds as anti-hyperglycemic (n = 5), on liver function (n = 4), cancers (n = 3), and on Neuroinflammation and Atherosclerosis (n = 2). Most of the included studies are animals or in-vitro investigations.ConclusionIn this review, we discuss the latest findings on the molecular mechanism of NS effecting the AMPK signaling pathway. We also focus on the therapeutic effects of NS, including the prevention and treatment of metabolic and pro-inflammatory disease by targeting the AMPK pathway.Graphical abstract     

The effects of grape seed extract on glycemic control,serum lipoproteins,inflammation, and body weight: A systematic review and meta‐analysis of randomized controlled trials

The aim of this systematic review and meta‐analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I‐square (I²) statistic. Data were pooled using a random‐effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta‐analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): ?2.01; 95% confidence interval (CI): ?3.14, ?0.86), total cholesterol (TC; WMD: ?6.03; 95% CI: ?9.71, ?2.35), low‐density lipoprotein (LDL) cholesterol (WMD: ?4.97; 95% CI: ?8.37, ?1.57), triglycerides (WMD: ?6.55; 95% CI: ?9.28, ?3.83), and C‐reactive protein (CRP) concentrations (WMD: ?0.81; 95% CI: ?1.25, ?0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta‐analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.     

The Effect of Resveratrol Supplementation on Cardio‐Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized,Double‐Blind Controlled Trial

The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25–30) were randomly assigned to receive 1000 mg/day trans‐resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (?7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (?0.97±1.91, μIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8‐week resveratrol supplementation produced useful effects on some cardio‐metabolic parameters in patients with T2DM. More studies are needed to confirm these findings.     

Soy,Soy Isoflavones,and Protein Intake in Relation to Mortality from All Causes,Cancers, and Cardiovascular Diseases: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

ObjectiveWe conducted a systematic review and dose–response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.MethodsOnline databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose–response associations. Between-study heterogeneity was assessed by I² value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.ResultsIn total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I²=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I²=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.ConclusionsSoy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.     

Effect of extremely low frequency magnetic field on antioxidant activity in plasma and red blood cells in spot welders

Objective  The purpose of this study was to determine a possible relation between exposure to extremely low frequency magnetic field (ELF-MF) and the human antioxidant activity. Methods  The total serum antioxidant status (TAS), red blood cells (RBCs) glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in 46 spot welders who were occupationally exposed to ELF-MF (magnetic field strength = 8.8–84 microTesla (μT), frequency = 50 Hertz (Hz) and electric field strength = 20–133 V/m). The results were compared with a nonexposed ELF-MF control group. The correlation between magnetic field strength and antioxidant activity in RBCs and plasma was then assessed. Results  No significant differences in TAS levels were observed (P value = 0.065). However, in RBCs of exposed group, a significant decrease in SOD and GPX activities was observed (P value = 0.001 and 0.003, respectively). This decrease was measured as 22 and 12.3%, respectively. Furthermore, a significant negative correlation between SOD/GPX activities and magnetic field intensity was observed (coefficients of SOD: −0.625, significance: 0.0001 and coefficients of GPX: −0.348, significance: 0.018). Conclusion  The results of this study indicate that ELF-MF could influence the RBC antioxidant activity and might act as an oxidative stressor. Intracellular antioxidant enzymes such as SOD and GPX were found to be the most important markers involving in this process. The influence of magnetic field on the antioxidant activity of RBCs might occur even at the recommended levels of exposure.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.     

Enhanced Loading and Release of Non‐Steroidal Anti‐Inflammatory Drugs from Silica‐Based Nanoparticle Carriers

Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non‐steroidal anti‐inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X‐ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA‐15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10–20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site.     

A systematic review on status of lead pollution and toxicity in Iran; Guidance for preventive measures

Lead is an old environmental metal which is presented everywhere and lead poisoning is an important health issue in many countries in the world including Iran. It is known as a silent environmental disease which can have life-long adverse health effects. In children, the most vulnerable population, mental development of children health effects is of the greatest influence. Low level lead exposure can significantly induce motor dysfunctions and cognitive impairment in children. The sources of lead exposure vary among countries. Occupational lead exposure is an important health issue in Iran and mine workers, employees of paint factories, workers of copying centers, drivers, and tile making factories are in higher risk of lead toxicity. Moreover lead processing industry has always been a major of concern which affects surface water, drinking waters, and ground waters, even water of Caspian Sea, Persian Gulf and rivers due to increasing the number of industries in vicinity of rivers that release their waste discharges into river or sea. In addition, lead contamination of soil and air especially in vicinity of polluted and industrialized cities is another health problem in Iran. Even foods such as rice and fishes, raw milk, and vegetables which are the most common food of Iranian population are polluted to lead in some area of Iran. Adding lead to the opium is a recently health hazard in Iran that has been observed among opium addicts. There are few studies evaluated current status of lead exposure and toxicity in the Iranian children and pregnant women which should be taken into account of authorities. We recommend to identify sources, eliminate or control sources, and monitor environmental exposures and hazards to prevent lead poisoning.