Histological and Electron Microscopic Study of the Postulated Protective Role of Green Tea Against DEHP Liver Toxicity in Mice

Di(2-ethylhexyl)phthalate [DEHP] is a plasticizer (softener) used to increase the flexibility of polyvinyl chloride (plastic). Animal studies following acute and chronic exposure of DEHP show several toxic changes in many organs including the liver. There have been no studies of compound specific techniques for reducing DEHP body burden. A study of the impact of dietary modifications (increased intake of antioxidants, zinc and glutathione precursors, and decreased dietary fat) on the effects of exposure to DEHP might be useful. Antioxidants effect of green tea was confirmed in many studies as a substance that protects the body from free radicals against degenerative changes by minimizing the amount of damage. This study was performed to evaluate the postulated protective effect of green tea against DEHP Liver toxicity in the mice on histological and ultra structural level. Results showed no significant differences in the mean of hepatocytes affection regarding necrosis or hydropic degeneration between 2nd, 3rd & 4th groups. Marked increase in amount of collagen fibers between hepatocytes and marked depleted glycogen contents in many hepatocytes were detected in 2nd, 3rd & 4th groups. Ulrastructral changes of the hepatocytes showed degenerated membranous organelles, destructed nuclear membrane and cytoplasmic necrosis in 2nd, 3rd & 4th groups. Many fat globules detected in the 3rd group were diminished in the 4th one. In conclusion, in-significant difference in hepatocytes affection existed between green tea control group, DEHP group & green tea/DEHP group. It is concluded that green tea has no antioxidant role against DEHP liver degeneration, in contrast it may have an oxidant role; further studies are needed

Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

This work aimed to evaluate the effect of diphenyl dimethyl bicarboxylate (DDB) and dexamethasone alone and in combination with praziquantel on various parasitological, immunological and pathological parameters reflecting disease severity and morbidity in murine schistosomiasis. DDB and dexamethasone had no effect on worm burden but altered tissue egg distribution. This indicates that, under the schedule used, neither drug interfered with the development of adult worms or oviposition, but both can modulate liver pathology. Dexamethasone resulted in a greater reduction in granuloma size than did DDB. Dexamethasone-treated mice also showed lower levels of serum gamma interferon (IFN-γ), interleukin-12 (IL-12) and IL-4, together with higher IL-10 levels, than infected untreated control animals. These data suggest that dexamethasone is a convenient and promising coadjuvant agent that results in decreased morbidity in murine schistosomiasis

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Histological and Electron Microscopic Study of the Postulated Protective Role of Green Tea Against DEHP Liver Toxicity in Mice

Di(2-ethylhexyl)phthalate [DEHP] is a plasticizer (softener) used to increase the flexibility of polyvinyl chloride (plastic). Animal studies following acute and chronic exposure of DEHP show several toxic changes in many organs including the liver. There have been no studies of compound specific techniques for reducing DEHP body burden. A study of the impact of dietary modifications (increased intake of antioxidants, zinc and glutathione precursors, and decreased dietary fat) on the effects of exposure to DEHP might be useful. Antioxidants effect of green tea was confirmed in many studies as a substance that protects the body from free radicals against degenerative changes by minimizing the amount of damage. This study was performed to evaluate the postulated protective effect of green tea against DEHP Liver toxicity in the mice on histological and ultra structural level. Results showed no significant differences in the mean of hepatocytes affection regarding necrosis or hydropic degeneration between 2nd, 3rd & 4th groups. Marked increase in amount of collagen fibers between hepatocytes and marked depleted glycogen contents in many hepatocytes were detected in 2nd, 3rd & 4th groups. Ulrastructral changes of the hepatocytes showed degenerated membranous organelles, destructed nuclear membrane and cytoplasmic necrosis in 2nd, 3rd & 4th groups. Many fat globules detected in the 3rd group were diminished in the 4th one. In conclusion, in-significant difference in hepatocytes affection existed between green tea control group, DEHP group & green tea/DEHP group. It is concluded that green tea has no antioxidant role against DEHP liver degeneration, in contrast it may have an oxidant role; further studies are needed

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

Introduction: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial- mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients. Methods: In this case-control study that was conducted in 2013-2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-β1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-β1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman's rank correlation coefficient (Spearman's rho). Results: Serum levels of TGF-β1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-β1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-β1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04). Conclusion: Increased TGF-β1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients

Differential expression of cell cycle regulators in HCVinfection and related hepatocellular carcinoma

AIM: To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS: Subjects of the current study included 50 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis (LC), and 30 cases of hepatitis C-related hepatocellular carcinoma (HCC) admitted to the Department of Hepato-Gastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were also included as normal controls. Laboratory investigations including urine and stool analysis, liver function tests and prothrombin concentration; serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1, Cyclin E, p21, p27 and Rb/p105 proteins. RESULTS: Normal wedge liver biopsies didn’t express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1, p21 and p27. Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC (P < 0.01) to HCC (P < 0.001) cases; meanwhile, Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity. The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well- and poorly-differentiated tumors. p21 showed only a nuclear pattern of staining, while, p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases. Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases (P < 0.001), between Cyclin D1 and Cyclin E in HCCs (P < 0.01); however, an inverse relationship was detected between Cyclin D1 and p21 or p27 (P < 0.001) and between p21 and Rb/p105 (P < 0.05) in HCCs. CONCLUSION: Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC; while, Cyclin E may be a useful marker formonitoring tumor behavior. p21 and p27 can be used as predictive markers for HCC. Furthermore, higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis