Toxicology of long-term and high-dose administration of methylphenidate on the kidney tissue - a histopathology and molecular study.

The present study aims to assess the influences of oral methylphenidate on kidney function and structure versus vehicle treatment in adult male rats. In this study, thirty adult male rats equally into two treatment groups divided randomly, and among them, MPH has been administered for 21 days, at doses of 20 mg/kg, and the control group has received salin. In renal, under the effect of MPH applying quantitative real-time PCR, we analyzed nephrotoxicity-related molecular pathways like autophagy, inflammation, and apoptosis. Moreover, the levels of GSH, CAT, and SOD were investigated as antioxidant enzymes. Afterward, stereological analysis in MPH-treated rats has been performed. Analysis of qPCR displayed inflammation, impaired autophagy, and enhanced apoptosis with histological changes in the kidney's tissue, also an important rise in the antioxidant enzymes' level. Besides, 20 mg/kg of MPH led to a decline in the mean of Bowman's space thickness and renal corpuscle's volume in comparison to the control rats. Collectively, our histological and molecular data implicit that in the kidney region, administrating of MPH evoked discriminative expression alterations in nephrotoxicity-associated signaling cascades, specifically autophagy, inflammation, and apoptosis paired with important damage to kidney tissue.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

Effect of Boswellia species on the metabolic syndrome: A review.

The metabolic syndrome, a cluster of metabolic disorders, includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia leading to insulin resistance, development of diabetes mellitus, and cardiovascular diseases. For the treatment of metabolic syndrome, traditional herbal medicines such as frankincense or Boswellia species have been used due to their anti-inflammatory, anti-oxidant, anti-obesity, antidiabetic, antihypertensive, and hypolipidemic properties. Based on the literature, published evidence up to 2020 about the therapeutic effects of Boswellia species on the metabolic disorder among Medline, Scopus, and Google Scholar were precisely evaluated by keywords such as obesity, diabetes, hyperglycemia, hypertension, blood pressure, dyslipidemia, metabolic syndrome, frankincense, and Boswellia. According to the results, Boswellia species have beneficial effects to control metabolic syndrome and its related disorders such as hyperglycemia, dyslipidemia, hypertension, obesity, diabetes, and its complications. Boswellia species by reducing the resistance to insulin and restoring pancreatic beta cells decrease blood glucose. Also, Boswellia species has antithrombotic and anticoagulant properties that regulate blood pressure. The anti-oxidant properties of Boswellia species modulate the blood lipid profile via reducing TNF-α, IL-1ß levels, and increasing the adiponectin level. The therapeutic and protective effects of Boswellia species on metabolic disorders were remarkably confirmed regarding decreasing hyperglycemia, hyperlipidemia, hypertension, and obesity.

Relationship Between Single-Nucleotide Polymorphisms of Tumor Necrosis Factor Alpha, Interleukin-10, Factor II and Factor V with Risk of Inhibitor Development in Patients with Severe Hemophilia A.

BACKGROUND: About one-fourth of patients with hemophilia A (HA) develop alloantibodies against factor (F) VIII, as the main treatment challenge. Here, we assessed the relationship between interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), FII and FV polymorphisms and risk of inhibitor formation in patients with severe HA. METHODS: We divided 39 patients with severe HA in two groups of case (n: 19) and control (n: 20). Genotyping was performed by multiplex amplification tetra arms refractory mutation systempolymerase chain reaction (ARMS-PCR) and PCR-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor development in codominant and dominant inheritance pattern. Moreover, TNFα rs1800629 A allele, decrease the risk of inhibitor formation, while IL10 rs1800896 A>G, FV rs6025 G>A, and FII rs1799963 G>A polymorphisms were not associated with risk of inhibitor development. CONCLUSION: It seems that TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor formation in Iranian patients with HA.

Hemophilia in Iran.

BACKGROUND: Hemophilia A (HA) and B (HB) are common bleeding disorders, Iran having the ninth largest such population in the world. A considerable number of studies have been performed on different aspects of their disorder. OBJECTIVE: The aim of the study was to gather all obtainable data about Iranian patients with HA and HB, including molecular studies, clinical presentations and treatment, and development and management of patients with inhibitor, to help better understand the disease and its management in other parts of the world. METHODS: For this review study, we searched MEDLINE and Scientific Information Database for English and Persian sources until 2015. RESULTS AND DISCUSSION: There are 5369 patients with HA and HB in Iran among which 4438 patients have HA. About one-fifth of HA patients' genes were analyzed and their underlying defects detected. Hemarthrosis, epistaxis, ecchymosis, and post-dental extraction bleeding are the most common clinical presentations. Bleeding was mainly managed by on-demand replacement therapy with factor VIII/factor IX (FVIII/FIX) concentrates or cryoprecipitate in HA, and fresh frozen plasma in HB in the absence of factor concentrate. Mean per capita for FVIII in HA patients is 1.56 IU, which is higher than the global per capita mean. However, mean per capita for FIX (0.24 IU) is lower than the global mean but highest among eastern Mediterranean countries. Replacement with plasma-derived components has led to infection in a large number of patients as well as inhibitor development against exogenous infusion of coagulation factors. According to a World Federation of Hemophilia survey, 223 HA and 6 HB patients in Iran have developed inhibitor and have been mainly managed by recombinant FVII (rFVIIa) and activated prothrombin-complex concentrate. CONCLUSION: Although this study was performed in Iranian patients, the large number thereof gives confidence that the results can be used more widely for other countries, especially in the developing world.