Lambda-cyhalothrin-induced pancreatic toxicity in adult albino rats.

Lambda-cyhalothrin (LCT) is one of the most frequently utilized pyrethroids. This study aimed to explore the toxic effects of subacute exposure to LCT on the pancreas and the hepatic glucose metabolism in adult male albino rats. 20 rats were equally grouped into; Control group and LCT group. The latter received LCT (61.2 mg/kg b.wt.), orally on a daily basis for 28 days. At the end of experiment, blood samples were collected for the determination of serum glucose and insulin levels. Pancreases were harvested and levels of malondialdehyde (MDA); catalase (CAT); superoxide dismutase (SOD); reduced glutathione (GSH); tumor necrosis factor-α (TNF-α); interleukin-6 (IL-6); nuclear factor erythroid 2-related factor 2 (Nrf2); heme oxygenase 1 (HO-1); and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were assessed. Also, liver samples were analyzed for the activity of glucose metabolism enzymes, glycogen content, and pyruvate and lactate concentrations. Histopathological and immunohistochemical examinations of pancreatic tissues were undertaken as well. Results revealed hyperglycemia, hypoinsulinemia, increased MDA, TNF-α, IL-6, and NF-κB levels, in association with reduced CAT, SOD, GSH, Nrf2, and HO-1 levels in LCT group. Liver analyses demonstrated a clear disturbance in the hepatic enzymes of glucose metabolism, diminished glycogen content, decreased pyruvate, and increased lactate concentrations. Besides, pancreatic islets displayed degenerative changes and ß-cells loss. Immunohistochemistry revealed diminished area percentage (%) of insulin and Nrf2 and increased TNF-α immunoreaction. In conclusion, subacute exposure to LCT induces pancreatic toxicity, mostly via oxidative and inflammatory mechanisms, and dysregulates hepatic glucose metabolism in albino rats.

Safety and efficacy of the combination of cryotherapy and photodynamic modalities with imiquimod in patients with actinic keratosis: a systematic review and meta-analysis.

INTRODUCTION: Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic modalities with imiquimod has been proven to be a potential therapeutic option for AKs. However, there is no comprehensive systematic study that discussed this concept in literature taking into consideration both efficacy and safety. EVIDENCE ACQUISITION: We performed a comprehensive search of the literature for studies assessing the efficacy and toxicity of the combinatorial tripartite regimen, consisting of cryotherapy and photodynamic modalities with imiquimod in AK. Metanalysis was performed using comprehensive meta-analysis version 3.0. EVIDENCE SYNTHESIS: After the screening of 1031 studies, five studies were included. Two trials compared the effect of imiquimod/cryotherapy versus cryotherapy alone or versus cryotherapy/vehicle. Our meta-analysis indicated that imiquimod/cryotherapy effectively induces complete clinical clearance in patients with AKs (OR: 6.26; 95%CI: 1.56-24.1; P=0.01). Moreover, another two studies, which were not meta-analyzed, indicated a substantial clinical clearance in the number of AK lesions in the imiquimod plus photodynamic therapy arm as compared to 5% imiquimod or PDT alone. No serious systemic adverse events were reported in all the treatment arms. CONCLUSIONS: Combined PDT or cryotherapy with imiquimod is more effective in the complete recovery of AK than treatment with imiquimod alone.

Betanin ameliorates fipronil-induced nephrotoxicity via activation of Nrf2-HO-1/NQO-1 pathway in albino rat model.

Fipronil (FPN) is phenylpyrazole insecticide extensively used to control a wide variety of pests. Betanin (BET) is a natural colorant with promising antioxidant and anti-inflammatory effects. This study aimed to investigate the potential protective effect of BET on FPN induced nephrotoxicity in adult male albino rats. Forty rats were assigned into 4 equal groups; Group I (Control); Group II (BET) received 20 mg/kg b.wt/day; Group III (FPN) received 4.8 mg/kg b.wt/day; and Group IV (BET/FPN). All treatments were given orally for 90 days. At the end of experiment, blood samples were collected for analysis of serum urea and creatinine. Kidneys were harvested for determination of kidney injury molecule-1(KIM-1) level; gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO-1); oxidative stress biomarkers including malondialdehyde (MDA), protein carbonyl content (PCC), catalase activity (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH). Histopathological examination and immunohistochemical investigation of Nrf2, nuclear factor kappa B (NF-κB), and caspase-3 were also undertaken. The results revealed kidney dysfunction, downregulation of Nrf2, HO-1, and NQO-1 genes, redox imbalance, structural damage, decreased Nrf2 and increased NF-κB immune-expression, in addition to strong caspase-3 immunoreactivity in FPN-treated group. In the combined group, BET co-administration resulted in functional and structural amelioration, up-regulation of Nrf2, HO-1, and NQO-1 genes, mitigation of redox imbalance, and strong anti-inflammatory and antiapoptotic effects. In conclusion, BET via activation of Nrf2-HO-1/NQO-1 pathway, exhibits beneficial antioxidant, anti-inflammatory, and antiapoptotic effects against FPN-induced nephrotoxicity.

Comparative study of oral versus parenteral crocin in mitigating acrolein-induced lung injury in albino rats.

Acrolein (Ac) is the second most commonly inhaled toxin, produced in smoke of fires, tobacco smoke, overheated oils, and fried foods; and usually associated with lung toxicity. Crocin (Cr) is a natural carotenoid with a direct antioxidant capacity. Yet, oral administration of crocin as a natural rout is doubtful, because of poor absorbability. Therefore, the current study aimed to compare the potential protective effect of oral versus intraperitoneal (ip) crocin in mitigating Ac-induced lung toxicity. 50 Adult rats were randomly divided into 5 equal groups; Control (oral-saline and ip-saline) group, Cr (oral-Cr and ip-Cr) group, Ac group, oral-Cr/Ac group, and ip-Cr/Ac group; for biochemical, histopathological, and immunohistochemical investigations. Results indicated increased oxidative stress and inflammatory biomarkers in lungs of Ac-treated group. Histopathological and immunohistochemical examinations revealed lung edema, infiltration, fibrosis, and altered expression of apoptotic and anti-apoptotic markers. Compared to oral-Cr/Ac group, the ip-Cr/Ac group demonstrated remarkable improvement in the oxidative, inflammatory, and apoptotic biomarkers, as well as the histopathological alterations. In conclusion, intraperitoneal crocin exerts a more protective effect on acrolein-induced lung toxicity than the orally administered crocin.

Implementation of an interactive mobile application to pilot a rapid assay to detect HIV drug resistance mutations in Kenya.

Usability is an overlooked aspect of implementing lab-based assays, particularly novel assays in low-resource-settings. Esoteric instructions can lead to irreproducible test results and patient harm. To address these issues, we developed a software application based on "Aquarium", a laboratory-operating system run on a computer tablet that provides step-by-step digital interactive instructions, protocol management, and sample tracking. Aquarium was paired with a near point-of-care HIV drug resistance test, "OLA-Simple", that detects mutations associated with virologic failure. In this observational study we evaluated the performance of Aquarium in guiding untrained users through the multi-step laboratory protocol with little supervision. To evaluate the training by Aquarium software we conducted a feasibility study in a laboratory at Coptic Hope Center in Nairobi, Kenya. Twelve volunteers who were unfamiliar with the kit performed the test on blinded samples (2 blood specimens; 5 codons/sample). Steps guided by Aquarium included: CD4+ T-Cell separation, PCR, ligation, detection, and interpretation of test results. Participants filled out a short survey regarding their demographics and experience with the software and kit. None of the laboratory technicians had prior experience performing CD4+ separation and 7/12 had no experience performing laboratory-based molecular assays. 12/12 isolated CD4+ T cells from whole blood with yields comparable to isolations performed by trained personnel. The OLA-Simple workflow was completed by all, with genotyping results interpreted correctly by unaided-eye in 108/120 (90%) and by software in 116/120 (97%) of codons analyzed. In the surveys, participants favorably assessed the use of software guidance. The Aquarium digital instructions enabled first-time users in Kenya to complete the OLA-simple kit workflow with minimal training. Aquarium could increase the accessibility of laboratory assays in low-resource-settings and potentially standardize implementation of clinical laboratory tests.

The ameliorative effect of Moringa oleifera oil on tributyltin-induced brain toxicity in albino rats.

Tributyltin (TBT) is an organotin compound widely used as a biocide in antifouling paints. Moringa oleifera oil (MOO) has a promising antioxidant potential, which necessitates further exploration. This study was conducted to investigate the potential protective effect of MOO against TBT-induced brain toxicity. The 30 rats were grouped into five groups (six each), Group I negative control, Group II positive control (vehicle), Group III MOO (5 ml/kg body weight [b.wt.]), Group IV TBT (10 mg/kg b.wt.), and Group V TBT & MOO. All treatments were given orally for 28 days. Thereafter, brains were exposed to oxidative stress and neurological parameters analyses. Histopathological and immunohistochemical (caspase-3, Bax, Bcl-2) examinations were also carried out. In rats administered TBT, increased malondialdehyde level, decreased reduced glutathione, and low total antioxidant capacity levels were in support of oxidative stress mechanism. Neurotoxicity was indicated by high nitric oxide level and increased acetylcholinestrase activity. Along with the histopathological alterations, the dysregulated expression of caspase-3, Bax, and Bcl-2 were indicative of the apoptotic mechanism mediated by TBT. Co-administration of MOO with TBT ameliorated the aforementioned toxic effects. In conclusion, TBT causes brain toxicity via oxidative, nitrosative, and apoptotic mechanisms. MOO demonstrates protective effect against TBT-induced brain toxicity mostly via potent antioxidant and antiapoptotic properties.

Cardiac Progenitor Cells.

Cardiovascular diseases top the list of fatal illnesses worldwide. Cardiac tissues is known to be one of te least proliferative in the human body, with very limited regenraive capacity. Stem cell therapy has shown great potential for treatment of cardiovascular diseases in the experimental setting, but success in human trials has been limited. Applications of stem cell therapy for cardiovascular regeneration necessitate understamding of the complex and unique structure of the heart unit, and the embryologic development of the heart muscles and vessels. This chapter aims to provide an insight into cardiac progenitor cells and their potential applications in regenerative medicine. It also provides an overview of the embryological development of cardiac tissue, and the major findings on the development of cardiac stem cells, their characterization, and differentiation, and their regenerative potential. It concludes with clinical applications in treating cardiac disease using different approaches, and concludes with areas for future research.

Short-term competency of aortic valve repair in Egyptian patients.

OBJECTIVES: In recent years, repair techniques for diseased aortic valves have received increasing attention. This study reports the short-term outcome of aortic valve repair (AVr) for three pathologic categories: rheumatic heart disease, aortic regurgitations (ARs) from subarterial ventricular septal defect (VSD), and infective endocarditis in order achieve the valve competency. METHODS: From January 2017 to March 2019, 30 patients underwent AVr with significant AR in the National Heart Institute (NHI) and Banha university. All patients underwent echocardiography before and after the procedure; 30 patients underwent AVr with significant AR, nine patients (30%) with juxta-arterial VSD, two patients (6.66%) with infective endocarditis (IE), and 19 patients (63.33%) with rheumatic aortic valve disease. For intraoperative transesophageal echocardiography and direct examination for better clarification of the anatomy and guidance of repair after cardiopulmonary bypass (CPB), annular repair, leaflet repair by shaving, plication, triangular resection, augmentation with the pericardium, and VSD closure were done. RESULTS: Only three patients developed aortic incompetence grade II, no in-hospital mortality; however, we had 3 months later mortality for one patient with IE, only one patient with rheumatic heart disease progressed from grade II to grade IV aortic incompetence (AI) and aortic valve replacement was done so AVr was successfully done for the subaortic VSD, rheumatic, and IE patients instead of replacement of the valve. CONCLUSIONS: In favor of AVr, good patient selection, amenable techniques for the suitable pathology will give a good target hence the aim of the work.

Beneficial effects of folic acid on the kidneys and testes of adult albino rats after exposure to methomyl.

The aim of this study was to evaluate the protective effect of folate against methomyl-induced toxicity on the kidneys and testes of male rats. Adult male albino rats were divided into four groups; Group I served as the control (vehicle), Group II received folic acid (1.1 mg per kg b.wt.), Group III methomyl (1 mg per kg b.wt.) and Group IV folic acid and methomyl. Treatments were administered via oral gavage on a daily basis for 14 weeks. Thereafter blood samples were collected and serum creatinine, testosterone and total antioxidant capacity (TAC) were determined. Animals were sacrificed and semen analysis was conducted. The kidneys and testes were excised and malondialdehyde (MDA) levels were determined. Histopathological and immunohistochemical analyses for caspase-3 were also undertaken. Methomyl treatment resulted in a significant (p < 0.001) elevation of creatinine and MDA levels and significant (p < 0.001) reduction in testosterone and TAC levels. Furthermore, methomyl caused a significant (p < 0.001) reduction in sperm quality. Histopathological examination indicated testicular and renal damage with strong immunoreactivity for caspase-3. Functional and tissue damage was prevented in rats treated with a combination of methomyl and folic acid. This is ascribed to the ability of folate to directly scavenge reactive oxygen species and indirectly enhance cellular redox homeostasis. This study identified that folic acid supplementation may have a beneficial effect in preventing or reducing the deleterious effects of methomyl exposure on kidney as well as testis structure and function. Future studies should focus on the fertility outcome/pregnancy index in rats.