Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.

Grafted Sertoli cells prevent neuronal cell death and memory loss induced by seizures.

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.

An Overview of the Current Hepatitis B Treatment Strategies after Liver Transplantation.

Currently, liver transplantation (LT) is considered as the only option for the treatment of patients with various causes of liver failure, including patients with chronic hepatitis B virus (HBV) infections. Overall, patients with HBV who undergo LT are at increased risk of hepatitis B infection recurrence. Although the current knowledge regarding the pathophysiology of this infection has been dramatically increased over the past few decades, it is still considered a complex disease process with varying degrees of clinical characteristics and changing patterns over time. There are various treatment strategies for preventing HBV recurrence in the LT setting. Generally, these regimens include oral nucleoside/ nucleotide analogues (NAs), hepatitis B immune globulin (HBIG), and vaccines or the combination of these drugs. The treatment strategy of choice should be based on cost-effectiveness, along with other patients underlying conditions. In this case, studies indicate that potent NAs are more cost-effective than HBIG in most case scenarios. In this article, we aimed to review the general medications used in the prophylaxis of the recurrence of HBV infection after LT.

Novel 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors: Synthesis, Docking Studies, Molecular Dynamics Simulation and Biological Activities.

BACKGROUND: HIV-1 integrase (IN) has been considered as an important target for the development of novel anti-HIV-1 drugs. OBJECTIVE: The aim of this study was to design novel groups of HIV IN inhibitors. METHODS: In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2- a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole ß-diketoacids as a well-known group of IN inhibitors. RESULTS: Based on in-vitro anti-HIV-1 activity in a cell-based assay, compounds 5, 6a and 6k displayed moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 µM, respectively. However, integrase inhibition assay showed that most of the analogues did not have significant effects against integrase enzyme except compound 5 with an IC50 value of 45 µM. Our results indicated that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 µM and SI of 175. Docking and molecular dynamics simulation studies were also performed to provide some insights into the probable mechanism of tested compounds. CONCLUSION: These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3- carboxylic acid derivatives may consider as promising lead compounds for the development of new anti-HIV-1 drugs.

An update on treatment options for primary sclerosing cholangitis.

Primary sclerosing cholangitis is a chronic cholestatic liver disease defined by strictures of the biliary tree which could ultimately lead to liver cirrhosis and cholangiocarcinoma. Although the exact underlying etiology of this disorder is not fully understood, the pathology is believed to be caused by immune mediated mechanisms. Growing body of evidence suggests several treatment modalities mainly focusing on the inflammation aspect of this disorder. However, there is still no consensus regarding the best treatment option for these patients. Thus, the present study aimed to review the current treatment options for patients with primary sclerosing cholangitis.

GRM7 polymorphisms are not associated with ischemic stroke in Iranian population.

Objectives: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.Methods: In the present study, we aimed at identification of association between Glutamate Metabotropic Receptor 7 (GRM7) and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.Results: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.Conclusion: Consequently, the assessed GRM7 variants are not implicated in risk of ischemic stroke in Iranian population.

Avocado-Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited.

Avocado and soybean unsaponifiables (ASU) constitute vegetable extracts made from fruits and seeds of avocado and soybean oil. Characterized by its potent anti-inflammatory effects, this ASU mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and slow-acting symptomatic treatment of hip and knee osteoarthritis; autoimmune diseases; diffuse scleroderma and scleroderma-like states (e.g., morphea, sclerodactyly, scleroderma in bands). Besides, it was reported that it can improve the mood and quality of life of postmenopausal women in reducing menopause-related symptoms. This article aims to summarize the studies on biological effects of the avocado-soybean unsaponifiable, its chemical composition, pharmacotherapy as well as applications in auto-immune, osteoarticular and menopausal disorders. Finally, we will also discuss on its safety, toxicological and regulatory practices.

Are Molecularly Imprinted Polymers (MIPs) Beneficial in Detection and Determination of Mycotoxins in Cereal Samples?

The process of matrix clean-up and extraction of analytes has a significant influence on the detection and determination of the analyte, especially in trace amounts. Molecularly imprinted polymers (MIPs) are solid particles that can absorb specific molecules regarding the template molecule used in the synthesis process of each type of MIP. As a result, they can be used in more effective and more specific solid-phase extraction processes. On the other hand, mycotoxins are second metabolites of molds and fungus which are potentially cytotoxic and/or genotoxic even in trace amounts, and due to extensive consumption of cereals and the great concern of public health, several methods were developed and currently are in the process of development to detect and determine the presence and amounts of mycotoxins in cereals. This review is aimed to investigate the application and efficacy of MIPs in detecting and determination of mycotoxins in cereals.

Dys-regulation of peripheral transcript levels of ecto-5'-nucleotidase in multiple sclerosis patients.

CD73, also entitled as ecto-5'-nucleotidase (NT5E), is an ecto-nucleotidase that contributes in the breakage of extracellular ATP to adenosine and the preservation of immune balance. In spite of acknowledged role for immune response imbalance in the pathogenesis of multiple sclerosis (MS), data regarding NT5E expression in MS patients are scarce. In the current study, we assessed expression of NT5E in peripheral blood of MS patients and healthy subjects to unravel its role in the pathogenesis of MS. Results of Multilevel Bayesian model showed no significant difference in NT5E expression between total MS patients and healthy subjects. However, its expression was significantly lower in male MS patients compared with male controls (P= 0.031, 95% credible intervals: [-6.93, -0.56]). No significant correlation was found between expression of NT5E and age in any study subgroups. Remarkably, NT5E transcript levels had 92.31% sensitivity and 80% specificity in diagnosis of MS disease. The diagnostic power of NT5E transcripts was 86.2% based on AUC values. Consequently, the current study indicates the role of NT5E in the pathogenesis of MS disease in male subjects. Moreover, expression level of this gene might be used as a putative marker especially in male MS patients.

Docking-based 3D-QSAR (CoMFA, CoMFA-RG, CoMSIA) study on hydroquinoline and thiazinan-4-one derivatives as selective COX-2 inhibitors.

A series of 26 selective COX-2 inhibitors which reported previously by our laboratory was selected to generate three-dimensional quantitative structure activity relationship (3D-QSAR) model. Active conformation of each molecule was predicted by docking studies and used for molecular alignment. Activity of 20 molecules as a train set was predicted using three methods including comparative molecular field analysis (CoMFA), CoMFA region focusing (CoMFA-RG) and comparative molecular similarity index analysis (CoMSIA). The best models of CoMFA-RG and CoMSIA revealed correlation coefficients r2 of 0.955 and 0.947, the leave one out cross-validation coefficients q2 of 0.573 and 0.574, respectively. In addition, CoMFA-RG and CoMSIA models were validated by a test set of six molecules with predicted coefficients r2pred of 0.644 and 0.799, respectively. Contour maps of generated models provided fruitful information about structural aspect of molecules that affected their COX-2 inhibitory activity. Based on three models results, steric and electrostatic properties are the most important factors in controlling the activity of the molecules. Results of CoMFA-RG and CoMSIA models were utilized to design new molecules. Comparison of experimental and predicted pIC50 values of designed molecules indicated that CoMFA-RG had the more predictive ability. Communicated by Ramaswamy H. Sarma.