Depression of glutamate and GABA release by presynaptic GABAB receptors in the entorhinal cortex in normal and chronically epileptic rats

Presynaptic GABA(B) receptors (GABA(B)R) control glutamate and GABA release at many synapses in the nervous system. In the present study we used whole-cell patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents in the presence of TTX to monitor glutamate and GABA release from synapses in layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the release of both transmitters was reduced by application of GABA(B)R agonists. Quantitatively, the depression of GABA release in layer II and layer V, and of glutamate release in layer V was similar, but glutamate release in layer II was depressed to a greater extent. The data suggest that the same GABA(B)R may be present on both GABA and glutamate terminals in the EC, but that the heteroreceptor may show a greater level of expression in layer II. Studies with GABA(B)R antagonists suggested that neither the auto- nor the heteroreceptor was consistently tonically activated by ambient GABA in the presence of TTX. Studies in EC slices from rats made chronically epileptic using a pilocarpine model of temporal lobe epilepsy revealed a reduced effectiveness of both auto- and heteroreceptor function in both layers. This could suggest that enhanced glutamate and GABA release in the EC may be associated with the development of the epileptic condition.     

Potential impacts of COVID-19 on reproductive health: Scientific findings and social dimension

COVID-19 virus is classified as a respiratory disease that can be mainly transmitted via respiratory droplets, however, there are recently published reports suggested its ability to transmit via sexual intercourse, assisted reproductive technology (ART) treatments, pregnancy, and nursing. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been detected. A significant concern was raised about whether COVID‐19 may affect female and male reproductive functions. These findings imposed more restrictions on social relationships between individuals even if inside the family, adding more physiologic load. In this context, there is a crucial need to identify the biological and behavioral reproductive risk factors associated with COVID­19 disease. Questions regarding the potential risks of sexual transmission during intercourse and/or application of ART, vertical transmission (throughout pregnancy, delivery, and breastfeeding), the health of pregnant and postpartum women, and fetal or postnatal health problems of neonates/children remain largely unanswered. The contribution of individuals to different social and economic activities depends on the maintenance of good quality life and health. The ongoing COVID-19 pandemic raised on the end of December 2019 has drastically affected different aspects of human wellbeing. The pandemic not only affected the health of individuals, but also negatively affected mental health and social interaction. This review illustrates: a) scientific findings related to the impact of the COVID-19 pandemic on the reproductive process, considering gender, hormonal balance, gonad functions, pregnancy, and ART, b) the sociosexual dimension of COVID-19 disease and precautions that should be taken to avoid infection via sexual transmission or vertical transmission, which may alleviate the fear associated with continuing normal social relationships and economic activities.     

Acinetobacter baumannii as a community foodborne pathogen: Peptide mass fingerprinting analysis,genotypic of biofilm formation and phenotypic pattern of antimicrobial resistance

Acinetobacter baumannii (A. baumannii) is one of the most common Gram-negative pathogens that represent a major threat to human life. Because the prevalence of Multidrug-resistant biofilm-forming A. baumannii is increasing all over the world, this may lead to outbreaks of hospital infections. Nonetheless, the role of raw meat as a reservoir for A. baumannii remains unclear. Here our research was aimed to exhibit the frequency, precise identification, and genotyping of biofilm-related genes as well as antimicrobial resistance of A. baumannii isolates of raw meat specimens. Fifty-five A. baumannii strains were recovered from 220 specimens of different animal meat and then identified by Peptide Mass Fingerprinting Technique (PMFT). All identified isolates were genotyped by the qPCR method for the existence of biofilm-related genes (ompA, bap, blaPER-1, csuE, csgA, and fimH). In addition, the antimicrobial resistance against A. baumannii was detected by the Kirby-Bauer method. Based on our findings, the frequency rate of 55 A. baumannii isolates was 46.55%, 32.50%, 15.00%, and 9.68% of sheep, chicken, cow, and camel raw meat samples, respectively. The PMFT was able to identify all strains by 100%. the percentages of csuE, ompA, bla_PER-1, bap, and csgA genes in biofilm and non-biofilm producer A. baumannii were 72.73%, 60%, 58.2%, 52.74%, and 25.45%, respectively. In contrast, the fimH was not detected in all non-biofilm and biofilm producer strains. The ompA, bap, blaPER-1, csgA were detected only in biofilm-producing A. baumannii isolates. The maximum degree of resistance was observed against amoxicillin/clavulanic acid (89.10%), gentamicin (74.55%), tetracycline (72.73%), ampicillin (65.45%), and tobramycin (52.73%). In conclusion, our investigation demonstrated the high incidence of multi-drug resistant A. baumannii in raw meat samples, with a high existence of biofilm-related virulence genes of ompA, bap, blaPER-1, csgA. Therefore, it has become necessary to take the control measures to limit the development of A. baumannii.     

Design,synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity

A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-d-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.     

Biodetoxification of coumaphos insecticide using immobilizedEscherichia coli expressing organophosphorus hydrolase enzyme on cell surface

Recently, we reported an improved technology for the degradation of organophosphate nerve agents using whole cells of genetically engineeredEscherichia coli that anchored and displayed the enzyme organophosphorus hydrolase on the cell surface. In this paper we report the immobilization of these cells on highly porous sintered glass beads and the subsequent application of the immobilized cell in a continuous-flow packed bed bioreactor for the biodetoxification of a widely used insecticide, coumaphos.     

Comparative study of the efficacy of pulsed electromagnetic field and low level laser therapy on mitogen-activated protein kinases

Mitogen-Activated Protein Kinases (MAPKs) consist of three major signaling members: extracellular signal-regulated kinase (ERK), p38 and C-JUN N-terminal kinase (JNK). We investigated physiological effects of Pulsed Electromagnetic Field Therapy (PEMFT) and Low Level Laser Therapy (LLLT) on human body, adopting the expression level of mitogen-activated protein kinases as an indicator via assessment of the activation levels of three major families of MAPKS, ERK, p38 and JNK in the peripheral lymphocytes of patients before and after the therapies. Assessment for the expression levels of MAPKs families' were done, in the peripheral lymphocytes of patients recently have appendectomy, using flow cytometric analysis of multiple signaling pathways, pre and post LLLT and PEMFT application (twice daily for 6 successive days) on the appendectomy wound. There were non-significant differences in the expression levels of MAPKs families' pre- therapies application. But there were significant increase in the ERK expression levels post application of LLLT compared to its pre application (p<0.01). Also, there was significant increase in the ERK, p38 and C-Jun N terminal expression level values post application of PEMFT compared to its pre application expression levels (p<0.01 for each). The present study demonstrates that PEMFT has a powerful healing effect more than LLLT as it increase the activation of ERK, P38 and C-Jun-N Terminal while LLLT only increase the activation of ERK. LLLT has more potent pain decreasing effect than PEMFT as it does not activate P38 pathway like PEMFT.     

COMU: A third generation of uronium‐type coupling reagents

COMU is a third generation of uronium‐type coupling reagent based on ethyl 2‐cyano‐2‐(hydroxyimino)acetate (Oxyma) as well as a morpholino carbon skeleton. The presence of the morpholino group has a marked influence on the solubility, stability and reactivity of the reagent. COMU performed extremely well in the presence of only 1 equiv. of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. The by‐products of COMU are water soluble and easily removed, making it an excellent choice of coupling reagent for solution‐phase peptide synthesis. Finally, COMU shows a less hazardous safety profile than benzotriazole‐based reagents, such as HATU and HBTU, which in addition exhibit unpredictable autocatalytic decompositions and therefore a higher risk of explosion. Furthermore, in contrast to benzotriazole‐based reagents, COMU is significantly less likely to cause allergic reaction. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Antimetabolites: Design,synthesis, and cytotoxic evaluation of novel dihydropyridine thioglycosides and pyridine thioglycosides

A convenient synthesis of a novel series of dihydropyridine and pyridine thioglycosides was developed. The evaluation of anti-proliferative activity against HepG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have antitumor activity, especially 5b, 5f, 5j, 5n, 7b, 7f, 7j, 7n, 8b, 8f, and 8j. The results of molecular docking reveal that these compounds have high binding affinity by hydrogen bond formation with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).