Publications by authors named "Amir Hooshang Mohammadpour"

73 Publications

Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects.

J Cardiovasc Dev Dis 2021 Feb 26;8(3). Epub 2021 Feb 26.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed.

Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed.

Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF.

Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.
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http://dx.doi.org/10.3390/jcdd8030024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996747PMC
February 2021

Application of inulin/Eudragit RS in 5-ASA pellet coating with tuned, sustained-release feature in an animal model of ulcerative colitis.

Int J Pharm 2021 Mar 2;597:120347. Epub 2021 Feb 2.

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

A tunable release of 5-aminosalicylic acid (5-ASA) could bring therapeutic benefits in the treatment of inflammatory bowel disease (IBD). A 3 factorial design was used to achieve a tuned delivery of 5-ASA pellets in the small and large intestine using a coating composed of inulin/Eudragit RS (RS). The ratio of inulin/RS and coating level were independent variables while the dependent variables were the percent of drug release at pH 1.2 in 2 h and total release of drug in 10 h at pH 6.8. 5-ASA release from pellets was examined at different pH levels and the therapeutic efficacy of the optimum pellets was compared to 5-ASA pellets of Pentasa in rats with ulcerative colitis. The inulin/RS of 18/82 at a coating level of 16% was found to be the optimum for delivery of the drug to the small and large intestine. The coated pellets offered a superior therapeutic outcome compared to uncoated pellets and Pentasa in terms of colitis activity index (CAI), and the colon's tissue enzymes of GSH and MDA. The optimum coating composed of inulin and RS could offer a tuned sustained release of 5-ASA throughout the small and large intestine with the sensitivity of drug release to microbial degradation.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120347DOI Listing
March 2021

Evaluation of the Cardioprotective Effect of Granulocyte Colony Stimulating Factor in Patients with Carbon Monoxide Poisoning.

Protein Pept Lett 2020 Oct 22. Epub 2020 Oct 22.

Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.

Background: Carbon monoxide (CO), which is well known as silent killer, has many toxic effects on organs with high rate of metabolism such as heart and brain. CO-induced cardiotoxicity resulted in a wide range of disabilities including electrocardiogram (ECG) abnormalities, elevation in level of cardiac enzymes, arrhythmias, impairment of left ventricular and myocardial infarction (MI). Cardio-protective effects of Granulocyte colony-stimulating factor (G-CSF) on infarcted heart was proved previously in various reports.

Objective: In this study, possible effect of G-CSF on cardiac function of patients with moderate to severe acute CO poisoning was investigated.

Methods: Cardioprotective effects of G-CSF in CO-poisoned patients was evaluated through ECG, Holter monitoring, echocardiography, and biochemical studies. Continuous intravenous infusion of G-CSF (90 µg/kg) and normal saline were administered respectively to treatment and placebo groups.

Results: The results demonstrated that in moderate to severe CO poisoning, myocardial injury is common. ECG changes (e.g., ST-segment and T-wave changes, QTC), cardiac arrhythmias (e.g., heart blocks and ventricular arrhythmias), serum level of Troponin I, left ventricular ejection fraction were determined after G-CSF administration. Frequencies of ST depression, inversion or flatting of T wave and QTC in ECG were significantly reduced after G-CSF treatment. In addition, in-cidence of cardiac arrhythmias due to CO poisoning were reduced after G-CSF treatment. However, G-CSF did not exert protective effects on TPI level and function of left ventricular in CO-poisoned patients.

Conclusion: GCSF could probably reduce CO-induced cardiac ischemia in patients with acute CO poisoning.
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http://dx.doi.org/10.2174/0929866527666201022112810DOI Listing
October 2020

Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review.

Eur J Clin Pharmacol 2021 Mar 6;77(3):275-289. Epub 2020 Oct 6.

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.

Background: Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this review, we try to summarize reports of antibacterial antibiotic-induced DRESS focusing on characteristics of DRESS induced by each antibiotic group.

Methods: The data were collected by searching PubMed/MEDLINE and ScienceDirect. The keywords used as search terms were "DRESS syndrome," "drug-induced hypersensitivity syndrome (DIHS)," "antibiotics," "antimicrobial," and names of various antimicrobial groups. Finally, 254 relevant cases with a definite or probable diagnosis of DRESS based on RegiSCAR criteria were found until 30 May 2020 and reviewed.

Results And Conclusion: Totally, 254 cases of antibacterial antibiotic-induced DRESS are reported. Most of them are related to antituberculosis drugs, vancomycin, and sulfonamides, respectively. Rash and fever were most frequent clinical findings. Eosinophilia and liver injury were the most reported hematologic and visceral organ involvement, respectively. Most of the patients are managed with systemic corticosteroids. The death occurred in 16 patients which most of them experienced liver or lung involvement. The reactivation of various viruses especially HHV-6 is reported in 33 cases. The mean latency period was 29 days. It is necessary to perform thorough epidemiological, genetic, and immunological studies, also systematic case review and causality assessment, as well as well-designed clinical trials for better management of antibiotic-induced DRESS.
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http://dx.doi.org/10.1007/s00228-020-03005-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537982PMC
March 2021

Evaluation of the Correlation between Serum Concentrations of Asymmetric Dimethylarginine and Corrected TIMI Frame Count in Patients with Slow Coronary Flow.

Int J Vasc Med 2020 19;2020:4592190. Epub 2020 Sep 19.

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Coronary slow flow (CSF) is an important angiographic entity that is characterized by delayed opacification of coronary arteries in the absence of epicardial occlusive disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. Elevated levels of ADMA cause the induction of endothelial dysfunction and thus promote atherosclerosis. This study was aimed at determining the role of ADMA in the development of CSF. One hundred twenty-nine subjects who fulfilled the inclusion criteria were enrolled in this study. According to coronary angiography results, these subjects were divided into five groups. The serum concentration of ADMA was measured in these subjects. In this study, there was no significant correlation between serum concentrations of ADMA and mean corrected TIMI frame count (CTFC) ( > 0.05). However, the ADMA level was significantly correlated with CTFC in the left anterior descending (LAD) coronary artery in patients with CSF ( = -0.381, = 0.045). Also, plasma ADMA levels were significantly higher in patients with CSF and without CAD compared to patients without CSF and with CAD (50-90%) ( = 0.034). Besides, serum concentrations of ADMA were significantly higher in subjects with BMI < 25 kg/m compared with those having BMI > 30 kg/m ( = 0.003). It was also shown that the levels of ADMA were significantly higher in subjects with age as a cardiovascular risk factor compared with those without this risk factor ( = 0.024). Further studies with larger population sizes are needed to confirm the present findings on the association between the serum concentrations of ADMA and CSF.
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http://dx.doi.org/10.1155/2020/4592190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520690PMC
September 2020

Application of Erythropoietin in Chronic Heart Failure Treatment.

Mini Rev Med Chem 2020 ;20(20):2080-2089

Department of Clinical Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Heart Failure (HF) is recognized as an important public health concern worldwide, especially in developed countries, due to its high rate of morbidity and mortality. Although new pharmacological and non-pharmacological agents have improved the clinical sequelae of HF in patients, its mortality remains high, especially among the elderly. Erythropoietin (EPO), a glycoprotein, besides its traditional role in promoting erythropoiesis and production of erythroid progenitors, its beneficial role in reducing infarct area and improving heart function through EPO-induced antiapoptotic and antioxidant effects have been increasingly recognized. This review gathers the evidence to date about the effectiveness of EPO in HF patients. In addition to the growing evidence of EPO in the treatment of HF in the animal studies for improving cardiac function and infarct size, more clinical studies are needed to assess the role of EPO treatment in the management of HF.
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http://dx.doi.org/10.2174/1389557520999200728155543DOI Listing
January 2020

A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19).

Naunyn Schmiedebergs Arch Pharmacol 2020 07 19;393(7):1137-1152. Epub 2020 May 19.

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.
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http://dx.doi.org/10.1007/s00210-020-01901-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235439PMC
July 2020

Assessment of Withania somnifera root extract efficacy in patients with generalized anxiety disorder: A randomized double-blind placebo-controlled trial.

Curr Clin Pharmacol 2020 Apr 13. Epub 2020 Apr 13.

Halal Research Center of IRI, FDA, Tehran. Iran.

Background: Anxiety disorders are the most universal psychiatric problems in the general population. Due to their chronic nature, these diseases are managed with a multi-drug regimen lasting for a long period of time. Medication discontinuation leads to 25% and 80% recurrence in the first month and the first year, respectively. Despite several treatment approaches, there is no specific and optimal method for patient management. Therefore, it is necessary to find some new theraputic approaches with fewer side effects. Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect. The aim of this study was to investigate the effect of W. somnifera root extract as an alternative therapy to reduce standard generalized anxiety disorder (GAD) symptoms.

Methods: Forty patients who met the inclusion criteria (with a confirmed diagnosis of GAD as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) took part in this randomized double-blind placebo-controlled trial and were randomly selected for participation in the treatment group (W. somnifera extract, 1g/day; n = 22) or the placebo group (n = 18). All patients were under treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and were prescribed one capsule of the extract or placebo per day for six weeks. The Hamilton anxiety rating scale (HAM-A) was used to assess the severity of GAD symptoms at baseline as well as the second and sixth weeks of the trial.

Results: Comparison of the HAM-A scores during the course of the trial revealed a significant amelioration ofHAM-A score in the treatment group versus placebo (14 and 8 units reduction, respectively (P < 0.05)). Moreover, there was a significant difference in the reduction of GAD score between the second (P =0.04) and sixth week (P =0.02) in the treatment group. The extract was safe and no adverse effect was observed during the trial.

Conclusion: W. somnifera extract offers some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD.
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http://dx.doi.org/10.2174/1574884715666200413120413DOI Listing
April 2020

Response to Letter to the Editor: "Evaluate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina".

Avicenna J Phytomed 2020 Mar-Apr;10(2):116-117

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103429PMC
April 2020

The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences.

Curr Med Chem 2021 ;28(1):137-151

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.
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http://dx.doi.org/10.2174/1389450121666200302095103DOI Listing
February 2021

Comparison of serum levels of asymmetric dimethylarginine between patients who take two types of atypical anti psychotics.

Med J Islam Repub Iran 2019 23;33:114. Epub 2019 Oct 23.

Pharmaceutical Instiute of Technology, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Schizophrenia is associated with increased cardiovascular morbidity. Asymmetric dimethylarginine (ADMA) has been suggested as a cardiovascular biomarker. Treatment with atypical antipsychotics can increase some traditional risk factors of coronary artery disease. In addition to traditional risk factors, this study is carried out as a comparison of serum levels of ADMA and non-traditional factors among patients who take two types of atypical antipsychotics. In this clinical study, 57 schizophrenic patients with multiple episodes and 20 healthy voluntaries that fulfilled inclusion and exclusion criteria were entered into the study. The patients were divided into 3 groups (18 patients received risperidone alone, 20 patients received clozapine alone and 19 patients did not receive any drug). Plasma concentrations of ADMA, high-sensitivity Creactive protein (hs-CRP) and homocysteine were measured through enzyme-linked immunosorbent assay (ELISA), and traditional risk factors of metabolic syndrome were measured. Mean age of participants was 46.08±12.54 years. Moreover, the traditional (High-density lipoprotein (HDL), total cholesterol, waistline, and Body Mass Index (BMI)) and non-traditional factors (Homocysteine, hs-CRP) and ADMA were higher in patients with schizophrenia compared to healthy group (p≤ 0.05). Also, in the clozapine group, all mentioned non-traditional factors and ADMA were significantly higher than other groups (p≤ 0.05). In the clozapine group, levels of non-traditional factors and ADMA were significantly higher which indicates these patients are at risk of cardiovascular disease.
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http://dx.doi.org/10.34171/mjiri.33.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946932PMC
October 2019

Development of an effective liposomal cholesterol ester transfer protein (CETP) vaccine for protecting against atherosclerosis in rabbit model.

Pharm Dev Technol 2020 Apr 26;25(4):432-439. Epub 2019 Dec 26.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Clinical trials of cholesterol ester transfer protein (CETP) peptide vaccine were stopped after disappointing results in humans due to the inadequacy of adjuvant aluminum hydroxide in stimulating the immune response against the self-antigen of CETP. To increase the efficacy of the CETP vaccine, we developed a novel liposomal form of tetanus toxoid-CETP (TT-CETP) peptide (Lip CETP) with well-characterized properties and high encapsulation efficiency. The vaccine efficacy against atherosclerosis was evaluated in rabbits challenged with a high cholesterol diet. Rabbits were immunized with Lip-CETP or liposome containing CETP with CpG ODN (Lip CETP/CpG). Control groups received empty liposomes or buffer. Anti-TT-CETP specific antibodies in serum were determined and gene expression of cytokine IFN-γ and IL-4 were measured in blood peripheral mononuclear cells. Therapeutic response was evaluated by titration of plasma lipoproteins during the study and pathologic analysis of aorta atherosclerotic lesions at the end. Lip-CETP/CpG elicited strong anti-TT-CETP antibodies and a higher IFN-γ level than the buffer. IL-4 was lower than the buffer in all vaccinated groups. Plasma lipoproteins showed no significant difference in the studied groups. Atherosclerosis thickness grade of the aorta was lower than the buffer group ( < 0.001) in rabbits vaccinated with Lip-CETP but not with Lip-CETP/CpG. In conclusion, Lip-CETP showed a strong atheroprotective effect.
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http://dx.doi.org/10.1080/10837450.2019.1706181DOI Listing
April 2020

Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review.

Curr Med Chem 2020 ;27(40):6825-6836

Halal Research Center of IRI, FDA, Tehran, Iran

Objective: This study aimed to systematically investigate whether anti-androgens could significantly reduce Obsessive-Compulsive Disorder (OCD) symptoms compared to placebo or usual care in OCD patients.

Methods: PubMed, EMBASE, CENTRAL and International Clinical Trials Registry Platform (ICTRP) databases were searched up to October 2018 using relevant keywords. All randomized and if not available non-randomized studies conducted on a population including OCD patients who were administered with anti-androgen, which reported changes in their symptoms, were included. The studies on compulsive hypersexuality were excluded. Required data were extracted from full-text of the included articles by two independent authors. One randomized and four non-randomized trials were found.

Results: The only randomized trial showed that flutamide, an anti-androgen agent, was effective in reducing compulsion scores in male OCD patients with comorbid Tourette syndrome, compared to placebo. Three out of four non-randomized trials showed that different anti-androgens including finasteride, cyproterone acetate and triptorelin were effective in reducing OCD symptoms. The only study, which failed to show the efficacy of an anti-androgen agent, administered OCD patients with flutamide. Despite the positive results, available studies provide the evidence with low quality based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach.

Conclusion: Available studies are not sufficient for a precise answer to our study question. There is still a need for further large randomized blinded clinical trials to evaluate the effectiveness of antiandrogens in OCD patients. It is recommended that gender, comorbidities and subscales of Yale- Brown Obsessive-Compulsive Score (Y-BOCS) should be considered in designing the studies and interpreting their results.
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http://dx.doi.org/10.2174/0929867326666191209142209DOI Listing
January 2021

Anti-inflammatory drugs in the prevention of post-operative atrial fibrillation: a literature review.

Inflammopharmacology 2020 Feb 31;28(1):111-129. Epub 2019 Oct 31.

Halal Research Center of IRI, FDA, Tehran, Iran.

Atrial fibrillation (AF) is a serious and common complication following heart surgery. Cardiac surgery triggers inflammation in the heart and makes it susceptible to the incidence of AF. Therefore, anti-inflammatory drugs may reduce the rate of AF incidence in the post-surgery conditions. Immunosuppressant agents, steroidal anti-inflammatory drugs (corticosteroids), non-aspirin non-steroid anti-inflammatory drugs (NSAIDs), colchicine and omega-3 unsaturated fatty acids (n-3 UFA) are drugs with well-known anti-inflammatory properties. The efficacy, safety and other aspects of using these drugs in the prevention of post-operative AF (POAF) have been reviewed here. Studies evaluating the efficacy of colchicine have shown that it could be effective in the prevention of POAF. However, there is a need for additional studies to find a colchicine regimen with optimal efficacy and higher tolerability. The use of corticosteroids may also be of value based on the most of meta-analyses. In the case of n-3 polyunsaturated fatty acids and NSAIDs, current data fail to support their efficacy in POAF prevention. Moreover, perioperative administration of NSAIDs may be associated with some severe safety considerations. Immunosuppressant agents have not been used for the prevention of POAF. Further studies are needed to find the most effective strategy for POAF prevention with the least safety considerations and the highest health benefits.
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http://dx.doi.org/10.1007/s10787-019-00653-xDOI Listing
February 2020

Preparation, in vitro and in vivo evaluation of PLGA/Chitosan based nano-complex as a novel insulin delivery formulation.

Int J Pharm 2019 Dec 17;572:118710. Epub 2019 Oct 17.

Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

The smart self-regulated drug delivery systems for insulin administration are desirable to achieve glycemic control, and decrease the long-term micro- and macro vascular complications. In this study, we developed an injectable nano-complex formulation for closed-loop insulin delivery after subcutaneous administration and release of insulin in response to increased blood glucose levels. The nano-complex was prepared by mixing oppositely charged chitosan and PLGA nanoparticles. PLGA nanoparticles were prepared using double-emulsion solvent diffusion method, and were loaded with glucose oxidase (GOx) and catalase (CAT) enzymes. These negatively charged particles decrease micro-environmental pH, by gluconic acid production in the glucose molecules presence. Positively charged chitosan nanoparticles were prepared using ionic gelation method, and were loaded with insulin. These nanoparticles (NPs) released insulin by dissociation in acidic pH caused by the GOx activity. Following in vitro studies, in vivo evaluation of nano-complex formulations in streptozocin induced diabetic rats showed significant glycemic regulation up to 98 h after subcutaneous administration.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118710DOI Listing
December 2019

Altered serum Zinc and Copper in Iranian Adults who were of normal weight but metabolically obese.

Sci Rep 2019 10 16;9(1):14874. Epub 2019 Oct 16.

Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Metabolically obese normal weight (MONW) individuals are potentially at increased risk of developing metabolic syndrome. Serum zinc and copper concentrations were assessed in individuals with MONW to determine whether MONW is associated with altered serum zinc and/or copper status. Normal weight subjects (total n = 2419; 1298 men and 1121 women), were recruited as part of Mashhad Stroke and Heart Association Disorder (MASHAD) Study cohort. They were divided into two groups according to the presence or absence of MetS, defined using IDF criteria. Serum zinc and copper concentrations were determined by atomic absorption. Of the 2419 normal weight adults, 377 had MetS. Of this group, 53.7% and 49.7% had a serum zinc <70 µg/dl (Q1) (p = 0.001) or a serum copper <79 µg/dl (Q1) respectively. Furthermore, 27.3% had a serum copper >131 µg/dl (Q4) (p = 0.034), and 18.8% had a serum zinc >95 µg/dl (Q4). Logistic regression analysis was performed to determine the odds ratio (OR) for an association of serum zinc, copper and zinc to copper ratio with MetS in normal weight subjects. The subjects with a serum zinc >95 µg/dl (Q4) had 0.386 [OR: 0.614(95%CI 0.457-0.823)] lower chance of MetS (p = 0.001) and the subjects with a serum copper >131 (Q4) had OR 1.423 (95% CI: 1.09-1.857) higher chance of MetS (p = 0.009). These data remained significant after adjustment for age and sex, for serum zinc and copper, respectively. Furthermore, our results strongly suggested that zinc and copper were the independent risk factor for metabolic syndrome in normal weight subjects. There is an imbalance between serum copper and zinc concentrations among individuals with MONW when compared with normal BMI individuals without MetS. This may increase the risk of individuals with MONW developing conditions associated with this imbalance, such as diabetes and cardiovascular disease.
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http://dx.doi.org/10.1038/s41598-019-51365-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795855PMC
October 2019

Effects of selective serotonin reuptake inhibitors on DNA damage in patients with depression.

J Psychopharmacol 2019 11 26;33(11):1364-1376. Epub 2019 Sep 26.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The relationship between depression and increased oxidative stress is well known. DNA damage by oxidation factors is an important cause of the aging process in psychiatric disorders.

Aims: Owing to the scarcity of human studies and high inconsistencies in studies of the effects of antidepressants on DNA damage, the current study was undertaken to investigate the effects of depression and its treatment on DNA damage.

Methods: In a 15-week open-label study of citalopram ( = 25) and sertraline ( = 20), levels of DNA damage were measured by comet assay, proinflammatory (Interlukin-6 (IL-6)) and oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)) markers by ELISA, and gene expression of base excision repair enzymes (8-oxoguanine glycosylase (OGG1) and poly (ADP)-ribose polymerase-1 (PARP1)) by quantitative real-time polymerase chain reaction in healthy control patients ( = 14), with depression at the baseline and the same patients after week 15.

Results: DNA damage, 8-OHdG, IL-6 and expression of PARP1 were elevated in patients with depression compared with the healthy controls ( < 0.001). Selective serotonin reuptake inhibitor (SSRI) therapy could significantly reduce the depression score ( < 0.01), DNA damage ( < 0.001), as well as 8-OHdG and IL-6 ( < 0.0001). Nevertheless, the expression of PARP1 and OGG1 showed no significant changes after treatment.

Conclusions: This is the first study on the effect of SSRIs on the DNA damage and some of the repair enzymes in depression. Based on the results, depression can cause increased DNA damage. This damage is followed by activation of compensatory mechanisms whereby the expression of DNA damage repair enzymes is elevated. Finally, the treatment of psychiatric disorder by antidepressants can lower the level of oxidative DNA damage.
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http://dx.doi.org/10.1177/0269881119874461DOI Listing
November 2019

Rare P376L variant in the SR-BI gene associates with HDL dysfunction and risk of cardiovascular disease.

Clin Biochem 2019 Nov 25;73:44-49. Epub 2019 Jun 25.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Scavenger receptor class B type 1 (SR-BI) encoded by SCARB1 gene serves as a multifunctional HDL receptor, facilitating the uptake of cholesteryl esters from HDL to the liver. Recent studies have identified the association between the P376L missense mutation of the SCARB1 gene with increased serum HDL-Cholesterol level. However, the contribution of this variant to the development of cardiovascular disease (CVD) remains unclear.

Objective: We have investigated the association between the P376L polymorphism with the properties of HDL and CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort.

Methods: Six hundred and fifteen individuals who had a median follow-up period of 7 years were recruited as part of the MASHAD cohort. Anthropometric, biochemical parameters and HDL lipid peroxidation (HDLox) were assessed. Genotyping was performed using TaqMan-real-time-PCR based method. The association of P376L-rs74830766 with cardiovascular-risk-factors and CVD events were evaluated.

Results: Carriers of the P376L variant were significantly more likely than non-carriers to develop CVD using multivariate analyses adjusted for traditional CVD risk factors defined as: age, sex, BMI, presence of diabetes, or hypertension, positive smoking habit, and total cholesterol (OR: 3.75, 95%CI: 1.76-7.98, p = 0.001). In an adjusted model, there was a two fold increase in cardiovascular endpoints among individuals who were heterozygous for the P376L variant (hazard ratio, 2.08; 95% CI, 1.12-to 3.84, p = 0.02). Although there was no association between the presence of the P376L variant and HDL-C level, serum HDLox, measured as dysfunctional HDL, was 13% higher among carriers of the P376L variant than non-carriers.

Conclusion: We have found that carriers of the P376L variant possessed higher HDLox and were at increased risk of CVD in a representative population-based cohort, as compared to non-carriers.
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http://dx.doi.org/10.1016/j.clinbiochem.2019.06.014DOI Listing
November 2019

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs.

J Cell Physiol 2019 11 24;234(11):19339-19351. Epub 2019 Apr 24.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP , Mdr and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.
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http://dx.doi.org/10.1002/jcp.28644DOI Listing
November 2019

The effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina: A randomized clinical trial.

Avicenna J Phytomed 2019 Jan-Feb;9(1):1-9

Department of Internal Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Inflammation along with oxidative stress has an important role in the pathophysiology of unstable angina which leads to acute myocardial infarction, arrhythmias and eventually heart failure. Curcumin has anti-inflammatory and anti-oxidant effects and thereby, it may reduce cardiovascular complications. This randomized controlled trial aimed to investigate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina.

Materials And Methods: Forty patients with unstable angina who met the trial inclusion and exclusion criteria, participated in this double-blind randomized clinical trial. The patients were randomized into two groups: curcumin (80 mg/day for 5days) and placebo (80 mg/day for 5days). Cardiac function was evaluated by two-dimensional echocardiography devices at baseline (immediately after hospitalization) and 5 days after the onset of the trial. Atrial and ventricular arrhythmias were recorded by Holter monitors in cardiology ward, Ghaem academic hospital, Mashhad, Iran. Progression to heart failure, myocardial infarction, and pulmonary and cardiopulmonary resuscitation events as well as mortality were recorded daily throughout the study.

Results: There were no significant differences between the two groups in atrial and ventricular arrhythmias (p=0.2), and other echocardiographic parameters (Ejection fraction, E, A, E/A ratio, Em, and pulmonary artery pressure) at baseline and five days after the start of the trial.

Conclusion: Nanocurcumin administered at the dose of 80 mg/day for five days had no effect in the incidence of cardiovascular complications in patients with unstable angina.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369319PMC
February 2019

High-density lipoprotein lipid peroxidation as a molecular signature of the risk for developing cardiovascular disease: Results from MASHAD cohort.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

High-density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three-hundred and thirty individuals who had a median follow-up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41-1.86; p < 0.001). For every increase in HDLox by 0.1 unit, there was an increase in CVD risk by 1.62-fold. In an adjusted analysis, there was a >2.5-fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox > 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88-3.94). Higher HDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population-based cohort.
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http://dx.doi.org/10.1002/jcp.28276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699926PMC
February 2019

Drug interactions of cola-containing drinks.

Clin Nutr 2019 12 10;38(6):2545-2551. Epub 2019 Feb 10.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Cola-containing drinks (CCDs) are among the most common drinks in the world. There are some reports on interactions between CCDs and some drugs. However, there is no review on reported and possible interactions of CCDs. Thus, this paper attempted to provide a comprehensive review on this subject. It is well-accepted that CCDs are acidic and contain caffeine. It has been suggested that these two properties potentiate interactions of CCDs with different drugs in the context of both pharmacodynamics and pharmacokinetic, which includes drug absorption, metabolism, and renal excretion of drugs. It has been shown that serum concentrations of MTX, clozapine, carbamazepine, phenytoin, and ibuprofen increased following CCD consumption; these interactions can be toxic. Additionally, it has been reported that serum levels of lithium and warfarin were decreased and their efficacy reduced when simultaneously administered with CCDs. Serum concentrations of erlotinib and different azoles, including itraconazol, posaconazole, and ketoconazole, have been shown to increase when these drugs were co-administered with a CCD. As proposed and discussed here, CCDs have the potential for interactions with numerous other drugs and thus clinicians should be aware of reported and potential interactions of CCDs with various medications in order to avoid adverse reactions and achieve expected clinical response.
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http://dx.doi.org/10.1016/j.clnu.2019.01.029DOI Listing
December 2019

Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers.

Spec Care Dentist 2019 Mar 14;39(2):166-172. Epub 2019 Feb 14.

Department of New Science and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Oral mucositis (OM) is a complication of head and neck cancer (HNC) therapy with negative impact on the quality of life. Although definitive treatment has not yet been established, there is interest towards the use of natural compounds owing to their few side effects. Curcumin has a variety of biological and pharmacological properties including anticancer and anti-inflammatory effects.

Aim: The aim of this study is to evaluate the effect of curcumin in the form of nanomicelle on OM in HNC patients receiving radiotherapy.

Methods: In this clinical trial, 32 HNC patients were allocated to case and control groups, and respectively received nanocurcumin or placebo during radiotherapy.

Results: We found a statistically significant difference in the severity of mucositis between the 2 groups at all visits. In contrast to the control-group patients, who all developed OM in the 2nd week of radiotherapy, only 32% of the case group developed OM with no obvious oral or systemic side effects.

Conclusion: Our data show that nanomicelle curcumin is an effective agent in the prevention of OM or reducing its severity. Thus, the administration of nanocurcumin can be considered as a reasonable approach to hinder the development of OM in HNC patients requiring radiotherapy.
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http://dx.doi.org/10.1111/scd.12358DOI Listing
March 2019

Association Between Trace Element Status and Depression in HTLV-1-Infected Patients: a Retrospective Cohort Study.

Biol Trace Elem Res 2019 Sep 4;191(1):75-80. Epub 2019 Feb 4.

Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Depression and Anxiety are two important public health problems that are known to be associated with viral infections. The association between the intake of nutrients such as zinc and copper with symptoms of depression has been studied previously. The aim of the current study was to investigate the association between depression with human T cell lymphotropic virus type 1 (HTLV-1) infection and serum content of zinc and copper in a large Iranian population cohort. The study population consisted of 279 HTLV-1-positive patients who were identified after recruitment as part of a large cohort study: the Mashhad Stroke and Heart Association Disorder (MASHAD) study. They were divided into two groups of diagnosed with or without depression based on their symptoms. Serum zinc and copper levels of all subjects were measured using the flame atomic absorption spectrometry. The population sample comprised of 279 individuals infected with HTLV-1 of whom 192 (68.8%) were women. The mean serum zinc in the group with and without depression was 78.69 ± 13.79 μg/dl and 86.87 ± 19.44 μg/dl, respectively (p < 0.001). Also, the serum copper level was higher in the depressive group (116.75 ± 39.56) than in the non-depressive group (104.76 ± 30.77) (p 0.004). The association between serum zinc and copper with depression in HTLV-1-infected patients which was shown in this study could be considered in the treatment strategies in these patients.
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http://dx.doi.org/10.1007/s12011-018-1613-6DOI Listing
September 2019

The change of immunosuppressive regimen from calcineurin inhibitors to mammalian target of rapamycin (mTOR) inhibitors and its effect on malignancy following heart transplantation.

Int Immunopharmacol 2019 Apr 31;69:150-158. Epub 2019 Jan 31.

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Malignancy is a significant cause of mortality after organ transplantation. There is an increased rate of malignancy following heart transplantation (HTx) compared to the general population and other organ transplant recipients. Post-HTx patients with a history of malignancy are also at a higher risk of developing new malignancies or exacerbation of their existing malignancies. Mammalian target of Rapamycin inhibitors (mTORIs) are newly introduced immunosuppressive drugs with a unique mechanism of action. By changing the immunosuppressive regimen from classic drugs, especially calcineurin inhibitors (CNIs) to mTORIs, the rate of developing de novo malignancies and the relapse of former malignancies is significantly reduced. However, issues like allograft function, total surveillance of patients, and post-transplantation complications should be considered during the conversion of drug regimens utilizing CNIs to drug regimens employing mTORIs. We reviewed different post-heart transplant maintenance immunosuppressive regimens and their effect on post-HTx malignancies with a focus on mTORIs, compared safety against effectiveness, and gathered conclusions based on our review of the literature, which may lead clinicians to make a better evidence-based decision regarding post-HTx maintenance immunosuppressive drug regimens. Overall, CNI to mTORI conversion in post-HTx maintenance immunosuppressive drug regimens was associated with a reduced rate of developing malignancy in post-HTx patients. Furthermore, nephrotoxicity decreased significantly while using mTORIs in combination with lower doses of CNIs and the rejection rate was equivalent to CNI-only regimens. In conclusion, mTORI-based maintenance immunosuppressive drug regimens seem to be safe and beneficial when considering efficacy vs. adverse effects, and all-cause mortality rates are significantly lower in patients switched to mTORIs when compared to CNI recipients.
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http://dx.doi.org/10.1016/j.intimp.2019.01.035DOI Listing
April 2019

Human T lymphotropic virus type 1 and risk of cardiovascular disease: High-density lipoprotein dysfunction versus serum HDL-C concentrations.

Biofactors 2019 May 29;45(3):374-380. Epub 2019 Jan 29.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

High-density lipoprotein (HDL) is thought to be protective against cardiovascular disease (CVD), and HDL dysfunction is considered to be a risk factor for CVD. It is unclear whether there is an association between Human T lymphotropic virus type 1 (HTLV1) infection and CVD risk. We have assessed HDL lipid peroxidation (HDLox) as a marker of HDL dysfunction and CVD risk in a subgroup of the MASHAD cohort study. One hundred and sixty two individuals including 50 subjects positive for HTLV1 infection and 112 individuals negative for HTLV1 infection were recruited. Anthropometric and biochemical parameters including serum hs-CRP, fasted lipid profile (HDL-C, LDL, triglycerides, and cholesterol), and fasting blood glucose were determined. Serum HDLox was also measured in the study participants. Multivariate analyses were used to evaluate the association between serum HDLox and HTLV1 infection. None of the traditional CVD risk factors were associated with HTLV1 infection, including serum HDL-C. However, serum HDLox was independently associated with the presence of HTLV1 infection. Logistic regression analysis showed that subjects who were positive for HTLV1 infection were also significantly more likely than uninfected individuals to have higher HDLox (odds ratio 9.35, 95%CI: 3.5-24.7; P < 0.001). HDLox was increased approximately 20% (P < 0.001) in infected subjects compared to the uninfected group. Serum HDLox is a marker of CVD risk factor and increased in individuals affected by HTLV1 infection compared to healthy subjects. © 2019 BioFactors, 45(3):374-380, 2019.
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http://dx.doi.org/10.1002/biof.1489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548577PMC
May 2019

Association between serum zinc and copper levels and antioxidant defense in subjects infected with human T-lymphotropic virus type 1.

J Blood Med 2019 27;10:29-35. Epub 2018 Dec 27.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran,

Introduction: Copper (Cu) and zinc (Zn) are important trace elements that are also structural ions of superoxide dismutase (SOD), which reduce oxidative stress. Zinc deficiency and excess copper have been reported to be associated with inflammation. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus, which is believed to cause systemic inflammation. The aim of this study is to measure levels of Zn, Cu, SOD, and prooxidant-antioxidant balance (PAB) in HTLV-1-positive patients and investigate the association between serum Zn and Cu concentrations and levels of oxidative stress in them.

Methods: The serum samples of 1,116 subjects who had participated in the "Mashhad Stroke and Heart Atherosclerotic Disorder" study, including 279 HTLV-1-positive and 837 HTLV-1-negative patients, were used. Levels of Zn, Cu, SOD, and PAB were measured.

Results: Zinc and SOD levels were lower in the HTLV-1-positive group; however, the difference was statistically significant only for the level of SOD (=0.003). On the other hand, levels of copper and PAB were significantly higher in HTLV-1 positive subjects; =0.004 and =0.002, respectively.

Conclusion: In HTLV-infected patients, serum Zn concentration is lower and Cu concentration is higher than healthy controls. This altered situation might be either primary or secondary to HTLV-1 infection, which should be investigated in larger studies. We showed that SOD is significantly lower in HTLV-1-infected subjects. As in some other viruses that evolve different mechanisms to potentiate virus replication by changing the physiologic condition of host cells, HTLV-1 too probably decreases the activity of copper-zinc SOD1 by suppressing its gene.
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http://dx.doi.org/10.2147/JBM.S184913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312056PMC
December 2018

Atrial fibrillation in β-thalassemia patients with a focus on the role of iron-overload and oxidative stress: A review.

J Cell Physiol 2019 08 10;234(8):12249-12266. Epub 2018 Dec 10.

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in β-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.
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http://dx.doi.org/10.1002/jcp.27968DOI Listing
August 2019

Safety and tolerability of carvacrol in healthy subjects: a phase I clinical study.

Drug Chem Toxicol 2021 Mar 29;44(2):177-189. Epub 2018 Nov 29.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

This study was designed to assess safety and tolerability of carvacrol in healthy individuals. Subjects were randomly divided into two groups receiving 1 and 2 mg/kg/day carvacrol. Before and after carvacrol administration, routine blood and urine laboratory tests and spirometry were performed for all participants. The results showed that one-month treatment with carvacrol did not significantly affect the measured variables. In the group receiving 1 mg/kg/day carvacrol, calcium, erythrocyte sedimentation rate (ESR), mean cell volume (MCV), hemoglobin (Hb), and hematocrit (HCT) levels were significantly reduced but creatinine phosphokinase (CPK) was significantly increased, after treatment compared to baseline values ( < 0.05- < 0.001). There was significant reductions in high-density lipoprotein cholesterol (HDL), total bilirubin, amylase, iron, red blood cells (RBC) count, and HCT after one-month treatment with 2 mg/kg/day carvacrol compared to pretreatment values ( < 0.05- < 0.01). Although, triglyceride (TG), phosphorus, lactate dehydrogenase (LDH), prothrombin time (PT), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly increased after treatment with carvacrol 1 mg/kg/day ( < 0.05- < 0.001), all post-treatment measured parameters were within normal range. Treatment with carvacrol 2 mg/kg/day for one month increased FEV ( < 0.05). Nevertheless, there was no significant difference in measured variables except LDH, MCH, MCHC, and MCV ( < 0.05- < 0.01), between the two groups. The results of this phase I study regarding carvacrol effects on healthy subjects, showed clinical safety and tolerability for this agent.
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http://dx.doi.org/10.1080/01480545.2018.1538233DOI Listing
March 2021