BACKGROUND: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island within the promoter region.

AIM: To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis.

PATIENTS AND METHODS: This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ(2)) test was performed. Exact test was used instead when the expected frequency was less than 5.

RESULTS: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 μg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size.

CONCLUSION: Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island within the promoter region.

AIM: To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis.

PATIENTS AND METHODS: This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ(2)) test was performed. Exact test was used instead when the expected frequency was less than 5.

RESULTS: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 μg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size.

CONCLUSION: Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC.

Recently, oxidative stress was implicated in the environmental contaminant Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity, however the mechanism is unclear. We investigated the role of oxidative stress-responsive microRNAs in DEHP-induced aberrations and the protective effect of the citrus flavonoid, hesperidin (HSP). Male Wistar rats were randomly allocated into four groups as vehicle-treated control, DEHP-alone group (500 mg/kg/day) for 30 days, and HSP (25 or 50 mg/kg) for 60 days; testicular damage was triggered by oral administration of DEHP (500 mg/kg/day) after thirty days of oral administration of HSP (25 or 50 mg/kg). DEHP administration reduced testis weight coefficient, serum testosterone, testicular 3β-hydroxysteroid dehydrogenase and antioxidant enzyme activities, and elevated serum fatty acid-binding protein-9, testicular malondialdehyde, and Bax/Bcl2 ratio. Aberrant testicular miR-126-3p and miR-181a expression was observed, along with decreased expression of sirtuin1 (SIRT1) and its targets; nuclear factor-erythroid 2-related factor2, haeme oxygenase-1, and superoxide dismutase2. HSP administration significantly ameliorated these changes and restored testicular function in a dose-dependent manner. We highlight a novel role of oxidative stress-miR-126/miR-181a-SIRT1 network in mediating DEHP-induced changes which were reversed by the antioxidant HSP.

Recently, oxidative stress was implicated in the environmental contaminant Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity, however the mechanism is unclear. We investigated the role of oxidative stress-responsive microRNAs in DEHP-induced aberrations and the protective effect of the citrus flavonoid, hesperidin (HSP). Male Wistar rats were randomly allocated into four groups as vehicle-treated control, DEHP-alone group (500 mg/kg/day) for 30 days, and HSP (25 or 50 mg/kg) for 60 days; testicular damage was triggered by oral administration of DEHP (500 mg/kg/day) after thirty days of oral administration of HSP (25 or 50 mg/kg). DEHP administration reduced testis weight coefficient, serum testosterone, testicular 3β-hydroxysteroid dehydrogenase and antioxidant enzyme activities, and elevated serum fatty acid-binding protein-9, testicular malondialdehyde, and Bax/Bcl2 ratio. Aberrant testicular miR-126-3p and miR-181a expression was observed, along with decreased expression of sirtuin1 (SIRT1) and its targets; nuclear factor-erythroid 2-related factor2, haeme oxygenase-1, and superoxide dismutase2. HSP administration significantly ameliorated these changes and restored testicular function in a dose-dependent manner. We highlight a novel role of oxidative stress-miR-126/miR-181a-SIRT1 network in mediating DEHP-induced changes which were reversed by the antioxidant HSP.

Recently, oxidative stress was implicated in the environmental contaminant Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity, however the mechanism is unclear. We investigated the role of oxidative stress-responsive microRNAs in DEHP-induced aberrations and the protective effect of the citrus flavonoid, hesperidin (HSP). Male Wistar rats were randomly allocated into four groups as vehicle-treated control, DEHP-alone group (500 mg/kg/day) for 30 days, and HSP (25 or 50 mg/kg) for 60 days; testicular damage was triggered by oral administration of DEHP (500 mg/kg/day) after thirty days of oral administration of HSP (25 or 50 mg/kg). DEHP administration reduced testis weight coefficient, serum testosterone, testicular 3β-hydroxysteroid dehydrogenase and antioxidant enzyme activities, and elevated serum fatty acid-binding protein-9, testicular malondialdehyde, and Bax/Bcl2 ratio. Aberrant testicular miR-126-3p and miR-181a expression was observed, along with decreased expression of sirtuin1 (SIRT1) and its targets; nuclear factor-erythroid 2-related factor2, haeme oxygenase-1, and superoxide dismutase2. HSP administration significantly ameliorated these changes and restored testicular function in a dose-dependent manner. We highlight a novel role of oxidative stress-miR-126/miR-181a-SIRT1 network in mediating DEHP-induced changes which were reversed by the antioxidant HSP.

Abstract Seed germination and growth of seedlings are critical phases of plant life that are adversely affected by various environmental cues. Water availability is one of the main factors that limit the productivity of many crops. This study was conducted to assess the changes in the sensitivity of chickpea seedlings to osmotic stress by prior treatment of chickpea seeds with a low concentration (50 ppm) of ellagic acid. Ellagic acid was isolated and purified from Padina boryana Thivy by chromatographic techniques. After ellagic acid treatment, seeds were germinated for 10 days under different osmotic potentials (0, -0.2, -0.4, -0.6 and -0.8 MPa) of polyethylene glycol (PEG) solutions. Ellagic acid treatment accelerated the germination and seedling growth of chickpea under osmotic stress conditions. Consistent with the accelerated growth, ellagic acid treated seedlings also showed a significant increase in the total antioxidant capacity (FRAP) as well as an increase in the compatible solutes (proline and glycine betaine) content. Additionally, treated seedlings revealed lower lipid peroxidation levels (MDA), electrolyte leakage (EL) and H2O2. Flavonoid and reduced glutathione (GSH) content, and the activity of antioxidant enzymes [catalase (CAT), peroxidase (POX), superoxide dismutase (SOD), glutathione reductase (GR)] and enzymes of the shikimic acid pathway [phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS)] all showed a remarkable increase with ellagic acid pretreatment compared to untreated seedlings especially under mild osmotic stress values (-0.2 and -0.4 MPa). These results suggested that treatment with ellagic acid could confer an increased tolerance of chickpea seedlings to osmotic stress, through reducing levels of \{H2O2\} and increasing antioxidant capacity.

BACKGROUND: The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss.

METHODS: Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA).

RESULTS: Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group.

CONCLUSIONS: In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition.

Background: The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss.
Methods: Fifty adult female Wistar rats with an average weight 150-200 g were randomized into 5 groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/ kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically histochemically and histomorphometrically. The bone mineral density was measured using DEXA.
Results: Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group.
Conclusions: In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition.

Supraclavicular nerve block (SCB) is a commonly used regional block for upper extremity surgery. The most common form of failure of SCB is ulnar segmental sparing. We aimed to evaluate the accuracy of perfusion index (PI) in early detection of segmental sparing of the ulnar component of SCB. A prospective observational study included adult patients scheduled for surgery under ultrasound-guided SCB. PI was simultaneously measured at the index finger and little finger. PI was recorded every minute for the first 10 min after SCB. PI ratio was calculated at every measurement point as PI/baseline PI. The area under the receiver operating characteristic (AUROC) curve was calculated for the ability of PI ratio to detect segmental ulnar sparing with comparison of little finger readings to the index finger readings. Forty-nine patients were available for the final analysis. Nine patients (18%) had segmental ulnar sparing. PI ratio at the little finger showed excellent predictive ability for ulnar sparing starting from the fifth minute (AUROC 0.92 [0.8-0.98], cutoff value ≤ 1.71) and reached the highest value at the seventh minute (AUROC 0.96 [0.86-1], cutoff value ≤ 1.35), whereas PI ratio at the index finger showed poor predictive ability. When using the PI for evaluation of successful SCB, segmental ulnar sparing could be accurately detected when the PI was measured at the little finger and not at the index finger. An increase of 71% in PI at the little finger 5 min after SCB could accurately rule out ulnar sparing.Clinical trial identifier NCT03880201. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03880201?term=NCT03880201&draw=2&rank=1 .

BACKGROUND: Fluid challenge test is a widely used method for the detection of fluid responsiveness in acute circulatory failure. However, detection of the patient's response to the fluid challenge requires monitoring of cardiac output which is not feasible in many settings. We investigated whether the changes in the pulse oximetry-derived peripheral perfusion index (PPI), as a non-invasive surrogate of cardiac output, can detect fluid responsiveness using the fluid challenge test or not.

METHODS: We prospectively enrolled 58 patients with septic shock on norepinephrine infusion. Fluid challenge test, using 200 mL crystalloid solution, was performed in all study subjects. All patients received an additional 300 mL crystalloid infusion to confirm fluid responsiveness. Velocity time integral (VTI) (using transthoracic echocardiography), and PPI were measured at the baseline, after 200 mL fluid challenge, and after completion of 500 mL crystalloids. Fluid responsiveness was defined by 10% increase in the VTI after completion of the 500 mL. The predictive ability of ∆PPI [Calculated as (PPI after 200 mL - baseline PPI)/baseline PPI] to detect fluid responders was obtained using the receiver operating characteristic curve.

RESULTS: Forty-two patients (74%) were fluid responders; in whom, the mean arterial pressure, the central venous pressure, the VTI, and the PPI increased after fluid administration compared to the baseline values. ∆PPI showed moderate ability to detect fluid responders [area under receiver operating characteristic curve (95% confidence interval) 0.82 (0.70-0.91), sensitivity 76%, specificity 80%, positive predictive value 92%, negative predictive value 54%, cutoff value ≥ 5%]. There was a significant correlation between ∆PPI and ∆VTI induced by the fluid challenge.

CONCLUSION: ∆PPI showed moderate ability to detect fluid responsiveness in patients with septic shock on norepinephrine infusion. Increased PPI after 200 mL crystalloid challenge can detect fluid responsiveness with a positive predictive value of 92%; however, failure of the PPI to increase does not exclude fluid responsiveness.

CLINICAL TRIAL IDENTIFIER: NCT03805321. Date of registration: 15 January 2019. Clinical trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03805321?term=ahmed+hasanin&rank=9 .