Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats.

BACKGROUND AND AIMS: Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF. METHOD: Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices. RESULT: MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001). CONCLUSION: Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity.

Neuroprotective Effects of Curcumin against Chronic ChlorpyrifosInduced Oxidative Damage in Rat Brain Tissue.

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. METHODS: Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. RESULTS: The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). CONCLUSION: Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

The Protective Effect of Curcumin Against Cardiotoxic Effects Induced by Chronic Exposure to Chlorpyrifos.

AIMS: This study aimed to evaluate the effect of Chlorpyrifos (CPF) in rat heart tissue and the effect of Curcumin (Cur) on cardiac enzymes, oxidative indices, and histopathological changes in the cardiac tissue. BACKGROUND: CPF, the most used organophosphorus pesticide (OP), has been reported to induce cardiotoxic effects. OBJECTIVE: The cardioprotective effects of Cur against CPF-induced toxicity have not been entirely investigated till now. METHOD: Forty male Wistar rats were randomized into five groups (n=8). C group (Control animals that received olive oil), CPF group (10 mg/kg/day), CPF + Cur 25, CPF + Cur 50, and CPF + Cur 100 groups (animals received 10 mg/kg/day CPF and 25, 50, and 100 mg/kg Cur, respectively). All treatments were administered via oral gavage for 90 days. Cardiac enzymes (LDH & CPK) and oxidative stress (OS) biomarkers in heart tissue (malondialdehyde, Superoxide Dismutase) were measured. Histopathological changes in the heart tissue were also evaluated. RESULT: Chronic exposure to CPF significantly increased cardiac enzyme levels and OS biomarkers. Histological changes were found, including disorganization of the cardiac muscle fibers with disorganization and degeneration in myocardial fibers with separation of myofibrils and cytoplasmic vacuolization of cardiac muscle fibers. Administration of Cur (100 mg/kg) reversed serum LDH concentration and OS biomarkers to normal levels in CPF-exposed animals (p < 0.05) and significantly improved cardiac damage. CONCLUSION: According to the results of this study, Cur can reduce the adverse effects of long-term exposure to CPF in rat heart tissue by modulating OS.

Evaluation of the hepatotoxicity of buprenorphine in rat pups born to an exposed mother during lactation.

Aim/ Background: This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients Objective: This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation. METHODS: BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation. RESULTS: The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP. CONCLUSION: In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

Evaluation Of The Effectiveness of Dantrolene Sodium against Digoxin-Induced Cardiotoxicity In Adult Rats.

BACKGROUND: Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the protective effect of dantrolene on digoxin-induced cardiotoxicity in male rats. METHODS: This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n=6) as follows:Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group), Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group),Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group), Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group), Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals&#039; cavernous sinus and each animal&#039;s heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20 oC. The heart samples were fixed in formalin 10% for histopathological evaluation. RESULTS: K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group (p < 0.001). dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group (p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group. CONCLUSION: dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene&#039;s cardioprotective and cardiotoxic doses in animal models.

Buprenorphine administration during gestation induces hepatotoxicity in the rat fetus.

This study investigated the effect of buprenorphine (BUP) on the livers of pups exposed to this drug during the fetal stage. BUP decreased the activities of serum liver enzymes in exposed animals versus the controls. BUP (0.5 mg/kg) decreased malondialdehyde levels and increased the glutathione levels in the liver of animals versus other groups. The superoxide dismutase activity was elevated in the BUP 0.5 mg/kg group versus the control group. BUP (1 mg/kg) induced histopathological changes in the livers of pups. In conclusion, BUP may induce hepatotoxicity in pups exposed to this drug during the fetal stage.

Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity in Rats: Biochemical and Histopathological Approaches in a Sub-chronic Study.

BACKGROUND: Chrysin (CH) is one of the important natural flavonoids with antioxidant and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos (CPF). METHODS: We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated CH at 12.5, 25, and 50 mg/kg/day for 45 days. RESULTS: In this study, CPF increased liver enzyme activities compared with the control group (p < 0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p < 0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the concentrations of MDA and NO in the CPF group was observed compared with the control group (p < 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p < 0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in the serum concentration of IL-6 compared with the control animals. No significant changes were found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration of CH plus CPF induced histopathological alterations in liver. CONCLUSION: These results suggest that CH attenuates hepatic enzymes and histopathological alterations induced by CPF via modulating oxidative stress and inflammatory indices in rats.

The effects of Berberis vulgaris L. and Berberis aristata L. in metabolic syndrome patients: a systematic and meta-analysis study.

INTRODUCTION: This meta-analysis study assessed the effects of Berberis vulgaris L. and Berberis aristata L. in patients with metabolic syndrome. METHODS: Data were analysed through "random-effects meta-regression" performance. RESULTS: The findings indicated that LDL was 0.68 and 2.92 lower in the B. vulgaris L. and B. aristata L.-treated groups versus the controls. The HDL was 0.71-fold higher in the B. aristata L.-treated group versus the controls. The total-cholesterol levels were 1.02 and 2.25 folds lower in the B. vulgaris L. and B. aristata L.-treated groups versus the matched control groups. The triglyceride levels were 1.35 and 1.16-fold lower in the B. vulgaris L. and B. aristata L.-treated groups versus the controls. Glucose was 0.96 and 0.54 folds lower in the B. vulgaris L. and B. aristata L.-treated groups versus the control groups, respectively. CONCLUSION: B. vulgaris L. and B. aristata L. have beneficial effects in patients with metabolic syndrome.

Aqueous extract of Teucrium polium ameliorates diabetes and induced-prostatic complication.

Purpose: Prostatic complications are common among diabetic patients. Previous research demonstrates that Teucrium polium (T. polium) has beneficial effects in diabetic cases. This study, therefore, aimed to evaluate the impacts of T. polium aqueous extract on the prostate of diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin (50 mg/kg). a total of 40 Rats were randomly divided into the following groups: Control, Control + TP100 (TP100), Diabetic, Diabetic + TP100 (DTP100) and Diabetic + TP200 (DTP200). The intervention was done orally once per day for 56 days (8 weeks). An oral glucose tolerance test was conducted, glucose and insulin levels were assessed. Microscopic features of the ventral prostatic lobe were evaluated pathologically. Results: T. polium at both doses significantly reduced glucose levels in an insulin-independent pathway. T. polium at both doses significantly improved prostate weight, prostate epithelium height, and prostate secretory activity in comparison with the diabetic group. Interestingly, treatment of T. polium to healthy rats led to decreased epithelial height. Conclusion: It could be deduced that T. polium has useful impacts on glucose control and may prevent prostatic complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-00979-4.

Curcumin and blood lipid levels: an updated systematic review and meta-analysis of randomised clinical trials.

The present study was designed to indicate the protective effects of curcumin on dyslipidemia. Main databases were searched to recognise randomised clinical trials evaluating the effect of curcumin on blood lipid profiles. The pooled odds ratio with a 95% confidence interval (CI) was used to evaluate the effect of curcumin on blood lipid parameters. HDL-C levels in the curcumin group were 0.04-fold lower than placebo (95% CI:-0.36-0.29; Z = 0.23; p = .82). LDL-C levels in the curcumin group reduced by 0.17 versus the placebo group (95% CI: -0.43-0.09; Z = 1.27; p = .2). TC levels in the curcumin group were 0.21 lower versus the placebo group (95% CI: -0.55-0.13; Z = 1.22; p = .22). TG level in the curcumin group were 0.05 lower versus the placebo (95% CI: -0.20-0.11; Z = 0.58; p = .56). This study suggests that curcumin may reduce blood lipid levels and can be used as a hypolipidemic agent.

Effects of exposure in utero to buprenorphine on oxidative stress and apoptosis in the hippocampus of rat pups.

The study investigated the effect of buprenorphine (BUP) on oxidative indices and gene expression of apoptotic molecules in the hippocampus of neonates during the fetal stage. BUP (1 or 0.5 mg/kg) was subcutaneously administrated to pregnant rat dams. After parturition, the pups were maintained to the end of breastfeeding period, then hippocampi were assessed for oxidative stress indices [glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total antioxidant capacity (TAC)] and mRNA expression of apoptotic markers (Bax, Bcl2 and caspase 3). Our data indicated that BUP (0.5 mg/kg) administration during gestation significantly increased GSH and TAC concentrations in the hippocampus of pups versus control group (p < 0.05). BUP (0.5 and 1 mg/kg) administration significantly elevated the expression levels of Bcl2 in the hippocampus of neonates compared with controls. BUP injection (0.5 and 1 mg/kg) to pregnant rats markedly reduced the expression levels of caspase 3 in the hippocampus of neonates in BUP 0.5 group (p < 0.01) and BUP 1 group (p < 0.05) versus the controls. Our study indicated that BUP may potentiate antioxidant system and inhibit apoptosis and oxidative stress in the hippocampus of neonates received this drug during the fetal stage.

Evaluation of family planning methods in married women with epilepsy.

BACKGROUND: Epilepsy is one of the most common neurologic unit diseases that have different prevalence in different parts of the world. Antiepileptic drugs (AEDs) are associated with major fertility risks for women of childbearing age. Due to the fact that studies on family planning methods in married women with epilepsy (WWE) have not been conducted in Iran, the aim of this study was to evaluate the family planning methods in married WWE in Birjand, Iran. METHODS: An analytical-descriptive study was performed on 126 married WWE hospitalized in the neurology ward or referred to Vali-e-Asr specialized and sub-specialized clinic in Birjand. Demographic information of patients as well as data on the type of used AED, and various methods of family planning were collected in a questionnaire. Data analysis was performed using Chi-square and Fisher tests. All of the above analyses were considered at a significance level of less than 5% by SPSS v.19 software. RESULTS: The mean age of the patients was 33.41 ±â€¯9.15 years. The mean age of experiencing the first seizure and the onset of menstruation were 24.82 and 13.79 years, respectively. Fifty (35.5%), 38 (27%), 15 (10.6%), 14 (9.9%), and 14 (9.9%) patients used sodium valproate, carbamazepine, phenytoin, levetiracetam, and lamotrigine, respectively. The results showed that 72 sexually active patients (70.6%) used family planning methods, of which 43 patients (59.7%) used withdrawal method, 20 patients (27.8%) used condoms, and 6 patients (8.3%) used oral contraceptive pills (OCP). Eight patients (9.6%) had a history of unintended pregnancy and 3 patients (3.6%) had a history of abortion. CONCLUSION: It is recommended to apply effective family planning methods in married WWE to prevent unintended pregnancies and the subsequent adverse effects in the fetus, considering the fact that a significant percentage of WWE did not use effective family planning methods and 8 cases of unintended pregnancies were reported. Because of high consumption of valproate in women of childbearing age in our study and concerning issue about its fetal malformation, it is recommended to reduce the administration of valproate in this population. Moreover, regarding the low consumption of folic acid, especially for women of childbearing age and pregnant WWE who are taking AED, the necessary recommendations should be made by our physicians.

Investigating the effect of the Teucrium polium aqueous extract on the liver of the streptozotocin-induced diabetic rats.

OBJECTIVES: Teucrium polium (TP) has been traditionally used for treatment of the diabetes mellitus, kidney and liver diseases, and inflammations but some studies have reported the hepatotoxicity effects of this plant. Therefore, this study was conducted to investigate the effect of TP aqueous extract on the liver of the diabetic rats. METHODS: Adult male Wistar rats were randomly divided into five groups: (Control) Normal rats that were gavaged with normal saline (1 mL), (TP100) Normal rats (Non-diabetic) that were gavaged with TP (100 mg/kg), (DM) diabetic model rats, which became diabetic by intraperitoneal injection of streptozotocin (50 mg/kg), (DTP100) diabetic rats that were gavaged with TP (100 mg/kg), and (DTP200) diabetic rats that were gavaged with TP (200 mg/kg). The effects of the aqueous extract on the blood glucose, body weight, the activities of enzyme markers of liver damage (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) were investigated in the serum of the control and treated groups. At the end of study liver histopathology and the total antioxidant activity (TAA) test were evaluated. Finally, obtained data were analyzed by the SPSS software (version 16). RESULTS: Results showed that the AST and ALT levels were significantly increased in the diabetic rats (p<0.001). A comparison of 100 mg/kg and 200 mg/kg doses of TP administration in diabetic rats also showed a significant difference (p=0.01), indicating a better performance of 100 mg/kg dose. No significant difference was found between the control group and rats treated by the TP (TP100) (p=0.382). Also, triglyceride (TG) and cholesterol levels were significantly decreased in the treated groups compared to the diabetic untreated group. CONCLUSIONS: Findings of the study revealed no hepatotoxicity, and the hepatoprotective effects of the TP were proved in the present study.

A systematic review on the metabolic effects of chlorpyrifos.

Organophosphate (OP) pesticides, including chlorpyrifos (CPF), can alter metabolic hemostasis. The current systematic study investigated blood glucose, lipid profiles, and body weight alterations in rodents and fish exposed to CPF. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines, querying online databases, including Web of Science, PubMed, and Scopus and also search engine including Google Scholar, through January 2021. Studies on rodent and fish exposed to CPF assessing metabolic functions were selected. All studies were in the English language, with other languages being excluded from the review. Two investigators independently assessed each of the articles. The first author's name, publication date, animal model, age, sample size, gender, dose, duration, and route of exposure and outcomes were extracted from each publication. The present review summarizes findings from 61 publications on glycemic, lipid profile, insulin, and body weight changes in rodents and fish exposed to CPF exposure. Most of the studies reported hyperglycemia, hyperlipidemia, and decreased insulin levels and body weight following exposure to CPF. Additionally, we confirmed that the CPF-induced metabolic alterations were both dose- and time-dependent. Our findings support an association between CPF exposure and metabolic diseases. However, more studies are needed to identify the metabolic-disrupting effects of CPF and their underlying mechanisms.

Metabolic impact of saffron and crocin: an updated systematic and meta-analysis of randomised clinical trials.

The present systematic and meta-analysis study was designed to show the protective impact of saffron and crocin supplementation on hyperlipidaemia and hyperglycaemia in randomised and clinical trials (RCTs). A pooled analysis using a model for random-effects showed that HDL-C levels were 0.21 fold higher in the saffron and 0.01 fold higher in the crocin group than placebo. LDL-C levels in the saffron group reduced by 0.51 and 0.04 fold in the crocin group versus the placebo. Moreover, TC levels in the saffron group were 0.19 lower and 0.11 fold lower in crocin group than in the placebo group. TG level in saffron group was 0.04 lower and 0.02 fold lower in crocin than the control group. The blood glucose levels did not significantly differ from the control group. This study suggests that saffron and crocin may modulate the serum lipid profile in patient with metabolic disorders.

Oxidative Stress Indices Changes in the Hearts of Rat Pups in Response to Maternal Buprenorphine Treatment during Gestation and Lactation.

This study aimed to assess the effects of Buprenorphine (BUP) on oxidative parameters in pups born to mothers exposed to the drug during gestation and lactation. Pregnant and lactating rats received BUP, 0.5 or 0.1 mg/kg subcutaneously for 21 and 28 days, respectively. At the end of the study, the pups were anesthetized, and the hearts were dissected out to measure oxidative stress indices, including the levels of Malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), and the activity of Superoxide dismutase (SOD). Our findings indicated that BUP did not alter MDA, NO, GSH levels, nor SOD activity in the cardiac tissue of pups exposed to this drug during the fetal period and through breast milk. We suggest performing additional studies to determine the association between BUP and oxidative modifications in cardiac tissues of pups born to mothers under BUP therapy during gestation and lactation.

High prevalence of multidrug-resistant non-fermentative Gram-negative bacilli harboring bla IMP-1 and bla VIM-1 metallo-beta-lactamase genes in Birjand, south-east Iran.

BACKGROUND AND OBJECTIVES: Non-fermentative Gram-negative Bacilli (NFGNB) is known as a major cause of healthcare-associated infections with high levels of antibiotic resistance. The aim of this study was to investigate the antibiotic resistance profiles and molecular characteristics of metallo-beta-lactamase (MBL)-producing NFGNB. MATERIALS AND METHODS: In this cross-sectional study, the antibiotic resistance profile of 122 clinical NFGNB isolates was determined by the Kirby-Bauer disk diffusion and microdilution broth methods. Bacterial isolates were investigated for the detection of MBLs production using the combination disk diffusion Test (CDDT). The existence of bla IMP, bla VIM, and bla NDM genes in all carbapenem-resistant isolates was determined employing polymerase chain reaction (PCR) assays. RESULTS: High resistance in Pseudomonas aeruginosa was reported to cefotaxime and minocycline, whereas Acinetobacter baumannii isolates were highly resistant to all antibiotics except colistin. Multidrug resistance (MDR)-NFGNB (66% vs. 12.5%, P=0.0004) and extensively drug resistant (XDR)-NFGNB (55.7% vs. 12.5%, P=0.001) isolates were significantly more common in hospitalized patients than in outpatients. The production of MBL was seen in 40% of P. aeruginosa and 93.3% of A. baumannii isolates. It was found that 33.3% and 46.7% of carbapenem-resistant P. aeruginosa isolates, and 13.3% and 28.9% of carbapenem-resistant A. baumannii isolates were harboring bla IMP-1 and bla VIM-1 genes, respectively. The incidence of MDR (98.2% vs. 28.3%, P<0.001) and XDR (96.4% vs. 11.7%, P<0.001) in MBL-producing NFGNB isolates was significantly higher than non-MBL-producing isolates. CONCLUSION: This study demonstrated a higher rate of resistance among NFGNB isolates with an additional burden of MBL production within them, warranting a need for robust microbiological surveillance and accurate detection of MBL producers among the NFGNB.

A systematic review of clinical and laboratory findings of lead poisoning: lessons from case reports.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.

Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials.

INTRODUCTION: Our aim was to investigate and evaluate the influence of metformin on cancer-related biomarkers in clinical trials. METHODS: This systematic study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Major databases, including Scopus, Web of Sciences, PubMed, Ovid-Medline, and Cochrane, were systematically reviewed by February 2020. Clinical trials investigating metformin effects on the evaluation of homeostatic models of insulin resistance (HOMA-IR), Ki-67, body mass index (BMI), fasting blood sugar (FBS), and insulin were selected for further analysis. Quality assessment was performed with version 2 of the Cochrane tool for determining the bias risk for randomized trials (RoB 2). Heterogeneity among the included studies was assessed using the Chi-square test. After quality assessment, a random effects model was performed to summarize the data related to insulin, HOMA-IR, Ki-67, and a fixed-effect model for FBS and BMI in a meta-analysis. RESULTS: Nine clinical trials with 716 patients with operable breast and endometrial cancer and 331 with primary breast cancer were involved in the current systematic and meta-analysis study. Systematic findings on the nine publications indicated metformin decreased insulin levels in four studies, FBS in one, BMI in two, Ki-67 in three studies, and HOMA-IR in two study. The pooled analysis indicated that metformin had no significant effect on the following values: insulin (standardized mean differences (SMD) = -0.87, 95% confidence intervals (CI) (-1.93, 0.19), p = 0.11), FBS (SMD = -0.18, 95% CI (-0.30, -0.05), p = 0.004), HOMA-IR (SMD = -0.17, 95% CI (-0.52, 0.19), p = 0.36), and BMI (SMD = -0.13, 95% CI (-0.28, 0.02), p = 0.09). Metformin could decrease Ki-67 in patients with operable endometrial cancer versus healthy subjects (SMD = 0.47, 95% CI (-1.82, 2.75), p = 30.1). According to Egger's test, no publication bias was observed for insulin, FBS, BMI, HOMA-IR, and Ki-67. CONCLUSIONS: Patients with operable breast and endometrial cancer under metformin therapy showed no significant changes in the investigated metabolic biomarkers in the most of included study. It was also found that metformin could decrease Ki-67 in patients with operable endometrial cancer. In comparison to the results obtained of our meta-analysis, due to the high heterogeneity and bias of the included clinical trials, the present findings could not confirm or reject the efficacy of metformin for patients with breast cancer and endometrial cancer.