Synthesis, anticancer activity, docking and computational studies of new pyridyl-glycosyl hybrids and acyclic analogs.

New pyridine-O-glycosides and their acyclic nucleoside analogues were prepared by heterocyclization and glycosylation. The anticancer activity against HCT-116, HepG2 and MCF-7 human cancer cells and BJ-1 cell revealed that the galacto- and xylopyranosyl glycosides possessing 4-bromophenyl have superior cytotoxic activities against HepG2 cell while glycosides 7-9 resulted in superior cytotoxic activities regarding MCF-7 breast cell. In case of HCT-116 colorectal carcinoma cells, two products and the derived glycosides and acyclic analogues showed potent activities. The most potent compounds were investigated for their possible binding affinities to the active site of CDK2 enzyme via in silico molecular docking simulation in addition to computational studies. The results support the antiproliferative effect and elucidate the interactions of 3a and 8 with catalytic sites.

[Box: see text].

Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.

Comparative effect of deliberate hypotensive anesthesia using nitroglycerine vs. phentolamine on event related potentials and cognitive functions in patients undergoing septoplasty: a randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction is a noteworthy complication of deliberate hypotensive anesthesia. The aim of this work was to compare the effect of deliberate hypotensive anesthesia using nitroglycerine versus phentolamine on event-related potentials and cognitive function in patients undergoing septoplasty surgery. METHODS: This prospective randomized controlled trial was conducted on 80 patients indicated for septoplasty under general anesthesia; 40 patients received intra-operative Nitroglycerine and 40 patients received intra-operative Phentolamine. Cognitive assessment (using Paired Associate Learning test (PALT) and Benton Visual Retention test (BVRT)) and P300 recording were done for all included patients pre-operatively and one week postoperatively. RESULTS: The scores of PALT and Benton BVRT significantly declined one week following surgery in both Nitroglycerine and Phentolamine groups. There was no statistically significant difference between Nitroglycerine and Phentolamine groups in the postoperative decline in either PALT or BVRT (P-value = 0.342, 0.662 respectively). The values of P300 latency showed a significant delay one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but in Nitroglycerine group, the delay is significantly higher than in Phentolamine group (P-value = 0.003). The values of P300 amplitude significantly decreased one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but there was no statistically significant difference between Nitroglycerine and Phentolamine groups (P-value = 0.099). CONCLUSION: Phentolamine is preferred over nitroglycerin in deliberate hypotensive anesthesia because it has less harmful effect on cognitive function than nitroglycerin.

Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar Rats via Suppressing the Oxidative Stress and Enhancing the Antioxidant Defense Mechanisms.

Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.

The Pathogenic Role of Oxidative Stress, Cytokine Expression, and Impaired Hematological Indices in Diabetic Cardiovascular Diseases.

A simultaneous increase in the prevalence of diabetes mellitus (DM), a risk factor for cardiovascular diseases (CVDs), has contributed to the escalation of CVD related mortalities. To date, oxidative stress and inflammation are increasingly recognized as significant drivers of cardiovascular complications in patients with diabetes. Therefore, this study aims to explore the correlation between oxidative stress, inflammation, and hematological indices in diabetic patients with CVDs. Patients were allocated into five groups: healthy controls; nondiabetic patients with myocardial infarction; diabetic patients with myocardial infarction; nondiabetic patients with heart failure; and diabetic patients with heart failure. The results revealed that the malondialdehyde levels were increased; whereas superoxide dismutase enzyme activities were markedly reduced in all CVD groups compared with those of healthy controls. Although the mRNA expression levels of interleukin (IL)-6, IL-18, and IL-38 were significantly increased, those of the anti-inflammatory cytokine, IL-35, have been reduced in all CVD groups compared with healthy controls. Regarding hematological indices, hematocrit, red blood cell distribution width, mean platelet (PLT) volume, plateletcrit, PLT distribution width, leukocyte count, and PLT-to-lymphocyte and neutrophil-to-lymphocyte ratios were markedly increased in the diabetic and nondiabetic CVD groups compared with those of the healthy controls. Oxidative stress and cytokine biomarkers may play a significant role in the complications of diabetic cardiomyopathy. Moreover, hematological indices are particularly sensitive to systemic inflammatory changes and are novel markers for the early detection of diabetic cardiomyopathy.

Cinnamaldehyde Mitigates Atherosclerosis Induced by High-Fat Diet via Modulation of Hyperlipidemia, Oxidative Stress, and Inflammation.

Atherosclerosis is a disease in which plaque builds up inside arteries. Cinnamaldehyde (Ci) has many biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to explore the protective effect of Ci against atherosclerosis induced by a high-fat diet (HFD) in Wistar rats. Atherosclerosis was induced by an oral administration of an HFD for 10 weeks. Atherosclerosis-induced rats were supplemented with Ci at a dose of 20 mg/kg bw dissolved in 0.5% dimethyl sulfoxide (DMSO), daily by oral gavage for the same period. Rats were divided into three groups of 10 rats each fed with (a) ND, (b) HFD, and (c) HFD+Ci, daily for 10 weeks. Treatment of rats with Ci significantly reduced the elevated levels of serum total cholesterol (T.Ch), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-Ch), very low-density lipoprotein-cholesterol (VLDL-Ch), and free fatty acids (FFAs) and significantly increased the lowered levels of high-density lipoprotein-cholesterol (HDL-Ch) level. Ci ameliorated the increased cardiovascular risk indices 1 and 2 and the decreased antiatherogenic index. Moreover, Ci reduced the elevated serum creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) activities. Ci also improved the heart antioxidant activities by decreasing malondialdehyde (MDA) and increasing glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (Gpx) activities. Furthermore, the supplementation with Ci downregulated the mRNA expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Thus, Ci successfully elicited a therapeutic impact against atherosclerosis induced by HFD via its hypolipidemic, antioxidant, and anti-inflammatory actions.

Anti-cancer and antimicrobial potential of five soil Streptomycetes: a metabolomics-based study.

Lack of new anti-cancer and anti-infective agents directed the pharmaceutical research to natural products' discovery especially from actinomycetes as one of the major sources of bioactive compounds. Metabolomics- and dereplication-guided approach has been used successfully in chemical profiling of bioactive actinomycetes. We aimed to study the metabolomic profile of five bioactive actinomycetes to investigate the interesting metabolites responsible for their antimicrobial and anti-cancer activities. Three actinomycetes, namely, Streptomyces sp. SH8, SH10 and SH13, were found to exhibit broad spectrum of antimicrobial activities, whereas isolate SH4 showed the broadest antimicrobial activity against all tested strains. In addition, isolates SH8, SH10 and SH12 displayed potent cytotoxicity against the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), whereas isolates SH4 and SH12 exhibited potent anti-cancer activity against the hepatoma cell line hepatoma G2 (HepG2) compared with their weak inhibitory properties on the normal breast cells MCF-10A and normal liver cells transformed human liver epithelial-2 (THLE2), respectively. All bioactive isolates were molecularly identified as Streptomyces sp. via 16S rRNA gene sequencing. Our actinobacterial dereplication analysis revealed putative identification of several bioactive metabolites including tetracycline, oxytetracycline and a macrolide antibiotic, novamethymycin. Together, chemical profiling of bioactive Streptomycetes via dereplication and metabolomics helped in assigning their unique metabolites and predicting the bioactive compounds instigating their diverse bioactivities.

The Effect of HCV Eradication after Direct-Acting Antiviral Agents on Hepatic Steatosis: A Prospective Observational Study.

BACKGROUND AND AIM: Eradication of hepatitis C virus (HCV) by direct-acting-antiviral- agents (DAAs) was followed by fibrosis regression, but little is available about hepatic steatosis changes after DAAs. The aim of this work was to assess the prevalence of hepatic steatosis among HCV Egyptian patients and the long term changes occuring after viral eradication. METHODS: This prospective cohort study included 150 HCV patients with significant fibrosis. They were examined by Transient elastography to evaluate liver stiffness measurement (LSM) and hepatic steatosis before treatment, at SVR12 and 1 year after the end of therapy. RESULTS: LSM showed a significant positive correlation to pretreatment of hepatic steatosis. LSM significantly decreased and hepatic steatosis significantly increased both at SVR12 and one year after DAAs. Patients with steatosis showed significantly higher median LSM and controlled attenuation parameter (CAP) values at: baseline, SVR12, and one year after therapy. Also, the pretreatment steatosis and body mass index (BMI) had a significant negative correlation with fibrosis regression one year after therapy in all studied groups. CONCLUSION: Hepatic steatosis is common in HCV Egyptian patients and increases after HCV eradication with DAAs. BMI and CAP values are negatively correlated to hepatic fibrosis regression and positively correlated to steatosis progression one year after DAAs. So, HCV patients with hepatic steatosis may need close follow up for atherosclerotic and HCC risk after DAAs, especially if they are overweight.

Morbidity and mortality during hepatitis C treatment using sofosbuvir and daclatasvir with or without ribavirin, in a cohort of Egyptian patients.

BACKGROUND: Though direct-acting antiviral agents (DAAs) therapy is associated with a high cure rate of hepatitis C virus infection, a potential risk of serious adverse events (SAEs) exists. The aim of this study was to determine the incidence and predictors of morbidity and mortality related to DAAs therapy. METHODS: This prospective study was conducted on a real word cohort of 1562 treatment naïve chronic hepatitis C (CHC) Egyptian patients, who received 12-weeks therapy with sofosbuvir (SOF) plus daclatasvir (DCV) ± ribavirin (RBV). The incidence and predictors of SAEs and mortality during treatment course and over the following 12 weeks were recorded. RESULTS: The mean age of study participants was 51.38 ± 9.70 years (55.22%, males). Liver cirrhosis was defined in 72.4% of participants. SAEs were recorded in 120 participants (7.68%), including hepatic decompensation, gastrointestinal bleeding, anemia and hepatocellular carcinoma. Nine patients (0.58%) died and 69 patients (4.42%) discontinued therapy due to SAEs. Severity of cirrhosis was the significant predictor of morbidities and mortality. Hepatic decompensation was predicted by baseline serum albumin [cutoff value: 3.00 g/dL, area under the receiver operating characteristic curve (AUROC): 0.953] and serum bilirubin (cutoff value: 1.75 mg/dL, AUROC: 0.940). CONCLUSION: The risk of morbidity and mortality related to SOF/DCV ± RBV therapy in CHC patients is small and is significantly linked to advanced cirrhosis.

Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: A pilot study.

OBJECTIVES: This is a randomized trial adopted to evaluate the safety and efficacy of immunization with specific anti-hepatocellular carcinoma dendritic cells (DCs) in Egyptian patients with advanced hepatocellular carcinoma (HCC) as a treatment or adjuvant therapy in comparison with the traditional therapy. METHODS: This study was conducted on 20 HCC patients who were assigned to four groups according to BCLC staging; group I: HCC patients (stage B) received trans-arterial chemoembolization (TACE) and DCs as an adjuvant therapy; group II: HCC patients (stage B) received TACE only; group III: advanced HCC patients (stage D) received DCs vaccine; group IV: advanced HCC patients (stage D) received supportive treatment. DCs were generated from peripheral blood monocytes and pulsed with a lysate of an allogeneic hepatic cancer cell line (HepG2). Toxicity and immunological response were reported as primary outcomes whereas clinical biochemical and radiological responses were reported as secondary outcomes. RESULTS: Our study detected that patients who received DCs vaccine (group III) showed mild decrease in Child-Pugh score as well as AFP and PIVKA II levels and developed 20% partial response [PR] 40% stable disease [SD] and 40% progressive disease [PD] compared to the patients of group IV on supportive treatment who developed 100% PD. Although group I patients developed PR (60%) SD (20%) and PD (20%) no significant difference was detected in the clinical biochemical or radiological response between group I and group II patients. DCs vaccine had minimal adverse effects with no autoimmunity and elicited a better immunological response such as increased CD8 cells percentage and number as well as decreased TGFß levels in the vaccinated patients. CONCLUSION: DCs vaccine is safe as it is not associated with significant toxicity. However due to the small number of included patients the efficacy and immune response of using DCs vaccine in the treatment of advanced HCC patients need to be justified by testing of a large cohort.

Predictors for Fibrosis Regression in Chronic HCV Patients after the Treatment with DAAS: Results of a Real-world Cohort Study.

INTRODUCTION: The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens. METHODS: This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients. RESULTS: Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one year of interferon containing and interferon free DAAs regimens respectively. Using multiple regression analysis; it was found that BMI, degrees of hepatic stiffness and steatosis were related to regression of hepatic fibrosis after therapy. CONCLUSION: DAAs with or without interferon resulted in a significant reduction of liver fibrosis. BMI, steatosis and liver stiffness were independent factors for fibrosis regression in chronic HCV patients treated with DAAs. Further studies are needed to explore the mechanism by which steatosis affects HCV related fibrosis regression after treatment with DAAs.

Long-standing nonulcerative bladder pain syndrome: Impact of Thiele massage on bladder and sexual domains.

PURPOSE: To assess the efficacy of Thiele massage (TM) as monotherapy for nonulcerative interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A prospective evaluation of 40 women with IC/BPS who underwent TM was conducted. TM was initially administrated by a physiotherapist and then self-administrated at home twice weekly for 16 weeks. Patients were assessed every 4 weeks on an outpatient basis. Assessment tools included 3-day voiding diaries, the Likert visual analog scale (VAS) for pain, and the Interstitial Cystitis Symptom Index (ICSI) and the Interstitial Cystitis Problem Index (ICPI) of the O'Leary-Sant questionnaire. Sexual function was assessed using the Female Sexual Function Index (FSFI). RESULTS: Thirty-six patients completed the study with a mean age ± SD 41.31 ± 9.93 (range 21-60 years). The mean duration of illness ± SD was 81.29 ± 34.55 (range 12-300 months). Perception of pain was higher than at basal level according to Likert VAS (9.2 ± 1.5 vs 9.8 ± 0.5, P = .018). The ICSI and ICPI questionnaires were deteriorated (16.83 ± 2.57 vs 12.89 ± 3.50, P = .015 and 15.75 ± 0.94 vs 14.31 ± 2.55, P < .001, respectively). TM had no significant impact on the total score of FSFI (P = .119); however, there was a negative impact on the lubrication domain with more dryness (0.045). CONCLUSIONS: TM is not an effective option as monotreatment modality for nonulcerative IC/BPS. An attempt of physiotherapy should be integrated in a multidisciplinary treatment.

Cardiac and pulmonary toxicity of mesoporous silica nanoparticles is associated with excessive ROS production and redox imbalance in Wistar rats.

Mesoporous silica nanoparticles (MSNs) represent one of the most promising drug delivery systems. MSNs have attracted considerable attention in recent years both in industry and biomedicine due to their unique properties. Thus, evaluation of the toxic effects of MSNs is necessary before the biomedical and clinical applications. We investigated the in vivo effect of MSNs on the production of reactive oxygen species (ROS), antioxidant defenses and histology of the heart and lung. Rats received 25, 50, 100 and 200 mg/kg body weight of synthesized MSNs intraperitoneally for 30 days and samples were collected for analysis. MSNs induced significant increase in serum cardiac function markers, tumor necrosis factor alpha and lipids. MSNs-induced rats exhibited anemia, thrombocytopenia, leukocytosis, significantly increased ROS, malondialdehyde and nitric oxide, and declined antioxidant defenses in the heart and lung of rats. In addition, MSNs induced histological alterations in the heart and lung of rats. In conclusion, our results demonstrated that MSNs induce cardiotoxicity and pulmonary toxicity via excessive generation of ROS, suppressed antioxidants, inflammation and histological alterations. Further investigations are recommended to understand the molecular mechanism underlying the toxic effects of MSNs and to improve the performance of nanomedicine.

Managing diabetes and liver disease association.

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.

Epidemiology of liver cancer in Nile delta over a decade: A single-center study.

BACKGROUND: In Egypt, there has been a remarkable increase in the proportion of hepatocellular carcinoma (HCC) among chronic liver diseases patients. This rising proportion may be explained by the increasing risk factors as hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, improvement of the diagnostic tools of HCC as well as the extended survival among patients with cirrhosis to allow time for some of them to develop HCC. The aim of this study was to study the epidemiology of HCC in Nile delta over the last decade. METHODS: The study was carried out on patients diagnosed as HCC in liver cancer clinic in Tanta University Hospital, Egypt, from January 2005 to January 2015. This retrospective study reviewed the files of HCC patients with special stress on age, sex, residence, occupation, smoking, and viral markers. RESULTS: Over the last decade, 1440 HCC patients were diagnosed or referred to liver cancer clinic in Tropical Medicine Department in Tanta University Hospital from January 2005 to January 2015. The mean age of HCC patients was 56.13 ± 9.53 years. Nearly, half of the patients with HCC were smokers and quarter of HCC patients were diabetics. HBV surface antigen-positive patients were only 3.26%, and the majority of patients were HCV-Ab positive (94.86% of patients). CONCLUSIONS: In Nile delta, hepatitis C rather than hepatitis B was linked to the development of HCC in our region which may be related to the high prevalence of HCV in this area.

Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt. PATIENTS AND METHODS: During the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum α-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI). RESULTS: Among 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening. CONCLUSION: The high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended.

Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis.

Screening endoscopy is recommended for early detection of esophageal varices (EVs) in cirrhotic patients with portal hypertension. However, this approach is limited by its invasiveness and cost. The aim of the study was to determine if platelet count can predict the presence of EVs, especially large (grade III, IV) EVs in need of prophylactic therapy, in a cohort of Egyptian patients with liver cirrhosis. In all, 110 patients with cirrhosis were prospectively analyzed. The presence of medium or large EVs was correlated with patients' platelet count and FIB-4. Esophageal varices were present in 87 (79.09%) patients. Among those with thrombocytopenia (platelet level below 150,000), 25.97% (20 patients) and 27.27% (21 patients) had EV grade II and EV grade III or IV, respectively. Whereas in patients in whom the platelet count was above 150,000, only 21.21% (7 patients) and 9.09% (3 patients) of patients had grade II EV and EV grade III or IV, respectively. A platelet count cut-off value of 149,000 was found to have specificity of 82% and sensitivity 39% for detection of presence of varices. A FIB-4 cut-off value of 3.175 was found to have an 83.3% sensitivity and 39.5% specificity in detecting large (grade III, IV) EVs. Platelet count is a noninvasive parameter with high accuracy for prediction of EVs. Cirrhotic patients with normal platelet counts (above 150,000), especially in financially deprived developing countries, can avoid screening endoscopy as they are at a low risk for variceal bleeding, and presence of large EVs in these patients is much less common than in those with thrombocytopenia. A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic banding in cirrhotic patients.

Spirulina versicolor improves insulin sensitivity and attenuates hyperglycemia-mediated oxidative stress in fructose-fed rats.

AIM: The current study aimed to investigate the anti-hyperglycemic, anti-hyperlipidemic and insulin sensitizing effects of the cyanobacterium Spirulina versicolor extract in fructose-fed rats. MATERIALS AND METHODS: Rats were fed 30% fructose solution in drinking water for 4 weeks. Animals exhibited hyperglycemia and hyperinsulinemia were selected for further investigations. Diabetic and control rats were orally supplemented with 50 mg/kg body weight S. versicolor extract for 4 weeks. RESULTS: At the end of 8 weeks, fructose-fed rats showed a significant increase in serum glucose, insulin, cholesterol, triglycerides, cardiovascular risk indices and insulin resistance. Treatment of the fructose-fed rats with S. versicolor extract improved this metabolic profile. Fructose feeding produced a significant increase in serum tumor necrosis factor alpha and a decrease in adiponectin levels. In addition, fructose-fed rats exhibited a significant increase in liver, kidney and heart lipid peroxidation levels, and declined antioxidant defenses. Supplementation of the fructose-fed rats with S. versicolor extract reversed these alterations. CONCLUSION: S. versicolor attenuates hyperglycemia-mediated oxidative stress and inflammation, and is thus effective in improving insulin sensitivity in fructose-fed rats.

GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC) cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS). Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS) and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS). Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM) mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA) metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

Evaluation of circulating ADH and MIC-1 as diagnostic markers in Egyptian patients with pancreatic cancer.

BACKGROUND: Despite the incidence rate of pancreatic cancer (PC) is uncommon in developing countries, it is considered as one of the most lethal disease. Improving patients' survival requires diagnosis of the disease at early stage. Therefore, it is imperative to identify more specific and sensitive marker(s) to be used for early detection of PC. OBJECTIVES: Our aim is to evaluate the potential role of circulating ADH and MIC-1 to be used as diagnostic markers in Egyptian patients and assess their value either alone or combined with CA19-9 in early detection of PC. METHODS: Alcohol dehydrogenase (ADH), macrophage inhibitory cytokine (MIC-1) and CA19-9 were measured by ELISA in serum procured from PC patients (n = 50) versus normal subjects (n = 20). RESULTS: Our results demonstrate that the circulating levels of ADH, MIC-1 and CA19-9 in blood of PC were significantly higher than in healthy controls (HCs) (p < 0.001). The highest marker sensitivity observed at early stage was MIC-1 (90%) and specificity was ADH (83%). The level of all three markers was elevated significantly in early stage of PC in comparison to HCs. The addition of ADH and MIC-1 to CA19-9 significantly improved the efficacy of diagnosis (p = 0.023). CONCLUSION: Our data demonstrate that not only the combination of ADH and MIC-1 to CA19-9 can be used in early detection of PC but also can improve the overall quality of diagnosis of this lethal disease.