Towards Understanding The Hepatoprotective effect of Grape Seeds Extract on Cholesterol-Fed Rats

Abstract: In our previous studies, a phenolic-rich extract of grape seed was prepared under optimal conditions. The antioxidant activity of grape seed extract (GSE) was determined in addition to 50 determination of acute oral LD toxicity. The current work studies the protective effect of GSE on hypercholesterolemia, where, W istar rats fed a standard laboratory diet (control group-CG) or a cholesterol-rich diet (hypercholesterolemic group-HCD) and to see the effect of GSE, another group fed on cholesterol-rich diet enriched with 0.3% GSEW /W-PG) for 8 weeks. Serum lipid levels, serum antioxidant status, Liver and kidney function were analysed in addition to histopathological examination of the liver. The hypocholesterolemic effects of GSE is confirmed by lowering the serum total cholesterol (TC) by 31%, low-density lipoprotein cholesterol LDL-C by 41% and elevated the high-density lipoprotein cholesterol HDL-C by 25% compared to TC, LDL-C and HDL-C of HCD group . Furthermore, the liver function expressed as glutamic pyruvate transaminase (GPT) and Albumin serum levels, decreased significantly and reached to normal level in case of oral administration of GSE. The kidney function showed no adverse effect in all groups. In addition, the antioxidant status serum level was increased as compared to those of rats fed only on cholesterol-rich diet. Histological examination of liver sections confirmed the serum analysis where GSE had a protective effect on animals fed on HCD, the liver of these animals showed mild affection in the form of microvesicular vacuolation of hepatocytes in the peripheral zone of the hepatic lobule (<50%) in comparison to the fatty change observed as microvesicular and macrovesicular vacuolation in >50% and <70% of the liver sections in HCD group. T hese results suggested that the GSE has a hypocholesterolemic effect which might be due to its ability to lower serum TC and LDL-C levels as well as slowing the lipid peroxidation process by enhancing antioxidant enzyme activity

Angiogenic output in viral hepatitis, C and B, and HCV-associated hepatocellular carcinoma

Introduction: Angiogenesis is known to play a pivotal role in most of malignancy, including HCC, and in chronic inflammation. Aim: To investigate the angiogenic output in HCV and HBV infection and its implication in the development of HCV associated HCC. Materials and methods: Blood samples were collected and grouped as; HS healthy subjects control group; HCC–HCV; chronic HCV infected patient group (HCV+ve) who are positive for serum anti-HCV antibodies and HCV–RNA; anti-HCV antibody positive and HCV–RNA negative patient group (HCV−ve); patients with positive HBsAg and HBV-DNA group (HBV+ve); and HBsAg positive and HBV-DNA negative patient group (HBV−ve). Serum levels of vascular endothelial growth factor, angiopoietin-2, endostatin and angiostatin were assessed in different studied groups. Results: The level of sVEGF was insignificantly elevated in both HCV+ve and HCV−ve groups when compared with controls, while Ang-2, sES and sAS were significantly elevated in both groups as compared with healthy controls. The studied parameters were significantly elevated in HBV-+ve patients when compared with the control. However, HBV−ve patients showed significantly elevated levels in sAng-2, sES and sAS when compared with the control while the level of sVEGF was equal to that of controls. In patients with HCC, the studied parameters showed a significant elevation when compared with healthy controls and patients either with HBV or HCV infection except for sAS in the case of HCV-+ve patients and VEGF for HBV-+ve patients who were also higher but not significant. Conclusion: The increased hepatic angiogenesis in chronic HCV and HBV could provide the molecular basis for liver carcinogenesis and contribute to the increased risk of HCC in patients with cirrhosis due to HCV and/or HBV

Modulation of NKG2D, KIR2DL and cytokine production by pleurotus ostreatus glucan enhances natural killer cell cytotoxicity toward cancer cells

Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate the possible immunomodulatory effects of mushroom polysaccharides on NK cells against different cancer cells. In this current study, fruiting bodies isolated from cultured Pleurotus ostreatus were extracted and partially purified using DEAE ion-exchange chromatography. The activation action of the collected fractions on Natural Killer cells was quantified against three different cancer cell lines in the presence or absence of human recombinant IL2 using three different activation and co-culture conditions. The possible modes of action of mushroom polysaccharides against cancer cells were evaluated at the cellular and molecular levels. Our results indicate that P. ostreatus polysaccharides induced NK-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%). NK cells activation for cytokine secretion was associated with upregulation of KIR2DL genes while the cytotoxic activation effect of NK cells against cancer cells correlated with NKG2D upregulation and induction of IFNγ and NO production. These cytotoxic effects were enhanced in the presence of IL2. Analysis of the most active partially purified fraction indicates that it is predominantly composed of glucans. These results indicate bioactive 6-linked glucans present in P. ostreatus extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive P. ostreatus polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research