Evaluation of Subacute Toxicity Induced by Methoxychlor: The protective Effect of Ascorbic acid

The present study was designed to detect the effects of sublethal concentration of Methoxychlor (MXC) on hematological constituents, thrombocytic indices, liver and kidney damage biomarker and erythrocytic oxidative status. As well as the possible protective effect of ascorbic acid (vit-C) were tested in rats at subacute period under laboratory conditions. MXC was administered orally at a dose of 200mg/kg, twice weekly, to male rats, for one month. Co – administration of ascorbic acid at a dose of 1g\L drinking water was achieved. MXC caused a significant reduction in hematological constituents and thrombocytic indices. MXC induced a significant increase in the serum alkaline phosphatase (ALP), gamma glutamyle transferase (γ-GT), uric acid and creatinine, whereas decrease in total protein and albumin levels. With regards, to the results of oxidative status revealed that decrease in superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities while increase in lipid peroxidation (LPO) components malondialdehyde (MDA). MXC plus vit-C treated group was significantly differed in most previous parameters than the MXC -treated group. These data, along with the determined changes suggest that MXC produce substantial systemic organ toxicity in rats during the period of a 30-days subacute exposure. The co- treatment with vit- C could ameliorate these toxic changes

Characterization of vacancy defects in Cu(In,Ga)Se2 by positron annihilation spectroscopy

The photovoltaic performance of Cu(In1-x,Gax)Se2 (CIGS) materials is commonly assumed to be degraded by the presence of vacancy-related defects. However, experimental identification of specific vacancy defects remains challenging. In this work we report positron lifetime measurements on CIGS crystals with x = 0, and x = 0.05, saturation trapping to two dominant vacancy defect types, in both types of crystal, is observed and found to be independent of temperature between 15–300 K. Atomic superposition method calculations of the positron lifetimes for a range of vacancy defects in CIS and CGS are reported. The calculated lifetimes support the assignment of the first experimental lifetime component to monovacancy or divacancy defects, and the second to trivacancies, or possibly the large In-Se divacancy. Further, the calculated positron parameters obtained here provide evidence that positron annihilation spectroscopy has the capability to identify specific vacancy-related defects in the Cu(In1-x,Gax)Se2 chalcogenides

Immunostimulatory and anti-inflammatory impact of Fragaria ananassa methanol extract in a rat model of cadmium chloride-induced pulmonary toxicity

Cadmium is an extremely dangerous heavy metal that can lead to disastrous consequences in all organisms. Several natural remedies reduce the toxicities of experimentally generated metals in animals. Strawberry Fragaria ananassa contains several bioactive compounds that may mitigate heavy-metal toxicity. The study aim was to evaluate the ability of a strawberry fruit methanol extract (SE) to reduce Cd toxicity and to identify and quantify the active constituents of SE. Forty Wistar rats were classified into four groups: the control group– 1 ml saline IP; SE group– 100 mg of SE/kg rats orally; cadmium (Cd) group–2 mg CdCl2/kg body weight/IP daily; and treated group– SE given 1 hour before Cd administration. Administration of Cd induced several histopathological and immunohistochemical alterations in lung sections. Biochemical analysis of lung homogenates and mRNA levels of antioxidants and inflammatory cytokines indicated significant changes to the risk profile. SE administration significantly decreased the oxidative stress, inflammation, tissue damage, the mean area percentage of collagen fibers, and positive immuno-expressions of TNF-α and NF-κB induced by CdCl2. Moreover, the MDA, TNF-α, GM-CSF, and IL-1β levels in Cd-exposed rat lung tissue were significantly lower in the SE-treated group than in the Cd-group. SE significantly augmented lung GSH, SOD, HO‐1, GPx-2, and Nrf2 levels in Cd-exposed rats. SE mitigated Cd-caused oxidative stress and lung inflammation. Therefore, regularly consuming a strawberry-rich diet could benefit general health and help prevent and treat diseases

Preoperative Evaluation of Thyroid Epithelial Lesions by DNA Ploidy and Galectin-3 Expression in FNAC

AIM: This study aimed to investigate the value of DNA ploidy and galectins-3 immunostain in the preoperative evaluation of thyroid epithelial lesions.MATERIAL AND METHODS: Sixty patients presenting with thyroid enlargement were included in this study and referred by clinicians for FNA. Routine cytological evaluation was done on PAP   stained slides according to the WHO criteria and at least three slides were prepared for routine cytological examinations. The nuclear DNA analysis was performed at the Pathology Department, National Research Center using the Leica Qwin 500 Image Analyzer (LEICA Imaging Systems Ltd, Cambridge, England). Galectin-3 expression was investigated in all tissues using streptavidin-biotin technique.RESULTS: Conventional Fine needle aspiration cytology (FNAC) of 60 cases could diagnose malignancy with a sensitivity of 60%, negative predictive value (NPV) 71.4%, and overall diagnostic accuracy of 80%. The aneuploidy was significantly associated with malignancy, with sensitivity 90.9%, specificity 83.3% and accuracy 88.3%. On using galectin-3 immunocytochemichal stain on cell blocks prepared from FNA the values were improved, sensitivity 93.3% specificity 86.7% and overall accuracy 90% and it was noticed that galectin-3 over expression was significantly associated with malignancy.CONCLUSIONS: From the results of this study we can consider that DNA ploidy and Galectin-3 could refine the FNA results and  increase its sensitivity as a screening test from sensitivity(60%) to reach sensitivity (93.3%), thus decreasing the false negative cases. From this study, it is concluded that the application of ancillary techniques as galectin-3 immunocytochemical markers may become a reliable indicator for surgical intervention, DNA ploidy measurements on the other hand may be of value in galectin-3 negative cases to determine the behavior of the lesion in such cases & refine the preoperative assessment by out ruling false negative cases

Top research priorities in liver and gallbladder disorders in the UK

OBJECTIVES: There is a mismatch between research questions considered important by patients, carers and healthcare professionals and the research performed in many fields of medicine. The non-alcohol-related liver and gallbladder disorders priority setting partnership was established to identify the top research priorities in the prevention, diagnostic and treatment of gallbladder disorders and liver disorders not covered by the James-Lind Alliance (JLA) alcohol-related liver disease priority setting partnership. DESIGN: The methods broadly followed the principles of the JLA guidebook. The one major deviation from the JLA methodology was the final step of identifying priorities: instead of prioritisation by group discussions at a consensus workshop involving stakeholders, the prioritisation was achieved by a modified Delphi consensus process. RESULTS: A total of 428 unique valid diagnostic or treatment research questions were identified. A literature review established that none of these questions were considered 'answered' that is, high-quality systematic reviews suggest that further research is not required on the topic. The Delphi panel achieved consensus (at least 80% Delphi panel members agreed) that a research question was a top research priority for six questions. Four additional research questions with highest proportion of Delphi panel members ranking the question as highly important were added to constitute the top 10 research priorities. CONCLUSIONS: A priority setting process involving patients, carers and healthcare professionals has been used to identify the top 10priority areas for research related to liver and gallbladder disorders. Basic, translational, clinical and public health research are required to address these uncertainties

Reversibility of liver fibrosis

Liver fibrosis, and its end stage cirrhosis are a major cause of morbidity and mortality and therapeutic options are limited. However, the traditional view of liver disease as an irreversible process is obsolete and it is now evident that the development of liver fibrosis is a dynamic and potentially bidirectional process. Spontaneous resolution of scarring is seen in animal models of liver fibrosis and in human trials in which the stimuli responsible for chronic or repeated hepatic inflammation is successfully removed. Key players in the process are hepatic stellate cells, macrophages, MMPs and their inhibitors Timps. It is also evident that in advanced fibrotic liver disease, specific histological features define what is currently described as "irreversible" fibrosis. This includes the development of paucicellular scars enriched in extensively cross-linked matrix components, such as fibrillar collagen and elastin. Our recent work has focused on the role of macrophage metalloelastase (MMP-12) in the turnover of elastin in reversible and irreversible models of fibrosis. We have shown that elastin turnover in liver injury and fibrosis is regulated by macrophages via Mmp-12 expression, activity and ratio to its inhibitor Timp-1. Failure of elastin degradation, together with increased deposition leads to accumulation of elastin in the fibrotic scars

Disordered protein-graphene oxide co-assembly and supramolecular biofabrication of functional fluidic devices

Supramolecular chemistry offers an exciting opportunity to assemble materials with molecular precision. However, there remains an unmet need to turn molecular self-assembly into functional materials and devices. Harnessing the inherent properties of both disordered proteins and graphene oxide (GO), we report a disordered protein-GO co-assembling system that through a diffusion-reaction process and disorder-to-order transitions generates hierarchically organized materials that exhibit high stability and access to non-equilibrium on demand. We use experimental approaches and molecular dynamics simulations to describe the underlying molecular mechanism of formation and establish key rules for its design and regulation. Through rapid prototyping techniques, we demonstrate the system's capacity to be controlled with spatio-temporal precision into well-defined capillary-like fluidic microstructures with a high level of biocompatibility and, importantly, the capacity to withstand flow. Our study presents an innovative approach to transform rational supramolecular design into functional engineering with potential widespread use in microfluidic systems and organ-on-a-chip platforms

Extra-corporeal membrane oxygenation for refractory cardiogenic shock after adult cardiac surgery:a systematic review and meta-analysis

Background - Postcardiotomy cardiogenic shock (PCCS) refractory to inotropic support and intra-aortic balloon pump (IABP) occurs rarely but is almost universally fatal without mechanical circulatory support. In this systematic review and meta-analysis we looked at the evidence behind the use of veno-arterial extra-corporeal membrane oxygenation (VA ECMO) in refractory PCCS from a patient survival rate and determinants of outcome viewpoint. Methods - A systematic review was performed in January 2017 using PubMed (with no defined time period) using the keywords “postcardiotomy”, “cardiogenic shock”, “extracorporeal membrane oxygenation” and “cardiac surgery”. We excluded papers pertaining to ECMO following paediatric cardiac surgery, medical causes of cardiogenic shock, as well as case reports, review articles, expert opinions, and letters to the editor. Once the studies were collated, a meta-analysis was performed on the proportion of survivors in those papers that met the inclusion criteria. Meta-regression was performed for the most commonly reported adverse prognostic indicators (API). Results - We identified 24 studies and a cumulative pool of 1926 patients from 1992 to 2016. We tabulated the demographic data, including the strengths and weaknesses for each of the studies, outcomes of VA ECMO for refractory PCCS, complications, and APIs. All the studies were retrospective cohort studies. Meta-analysis of the moderately heterogeneous data (95% CI 0.29 to 0.34, p 70 years, 95% CI −0.057 to 0.001, P = 0.058), and long ECMO support (95% CI −0.068 to 0.166, P = 0.412). Postoperative renal failure, high EuroSCORE (>20%), diabetes mellitus, obesity, rising lactate whilst on ECMO, gastrointestinal complications had also been reported. Conclusion - Haemodynamic support with VA ECMO provides a survival benefit with reasonable intermediate and long-term outcomes. Many studies had reported advanced age, renal failure and prolonged VA ECMO support as the most likely APIs for VA ECMO in PCCS. EuroSCORE can be utilized to anticipate the need for prophylactic perioperative VA ECMO in the high-risk category. APIs can be used to aid decision-making regarding both the institution and weaning of ECMO for refractory PCCS