Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients

Background: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment.

Methods: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment.

Results: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL.

Conclusion: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.     

Immunohistochemical Expression of Cathepsin L in Atopic Dermatitis and Lichen Planus

Background:

Cathepsin L is a member of papain superfamily. It seems to promote T-cell survival, selection maturation in the thymus and enhance the antigen presentation. Cathepsin L plays an important role in tumor necrosis factors (TNF-α) induced cell death. Also it degrades the tight junction between cornedesomses in the epidermis. Elevated expression of cathepsin L has been found in many inflammatory and neoplastic diseases.

Objective:

The aim of this study was to determine immunohistochemical expression of cathepsin L in atopic dermatitis (AD) and lichen planus (LP) patients in order to evaluate its role in the pathogenesis of both diseases.

Materials and Methods:

This study included 15 patients with AD (Group I), 15 patients with LP (Group II), in addition to 10 healthy skin specimens served as controls (Group III). Punch biopsies were taken from lesional skin of the patients and controls for immunohistochemical detection of cathepsin L expression.

Results:

Highly significant increase was found in cathepsin L expression in AD and LP patients compared to controls [P = 0.001].

Conclusion:

Cathepsin L could be implicated as an important protease in the pathogenesis of AD and LP. It could be a useful marker for assessing AD severity.     

Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models.     

New therapeutic aspect for carvedilol: antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation.     

Intravascular laser speckle imaging catheter for the mechanical evaluation of the arterial wall

Laser speckle imaging (LSI) is a novel technique for measuring the mechanical properties of atherosclerotic plaques. In LSI, the decorrelation time constant of speckle intensity fluctuations provides an index of viscoelasticity that is closely related to plaque microstructure and composition. Here, we demonstrate for the first time, the feasibility of conducting LSI in vivo using a prototype 1.5 mm (4.5 Fr) diameter intravascular catheter. Investigation of the catheter performance using human arterial samples ex vivo shows that plaque time constants measured by the LSI catheter correlate well with those measured using a free-space bulk optics system. To demonstrate LSI in vivo, the catheter is interfaced with a portable console for intravascular evaluation in the aorta of a living rabbit. Distinct differences in arterial time constants are identified at normal aortic and stented sites in vivo with intravascular LSI.     

Silent central nervous system involvement in Egyptian Behçet's disease patients: clinical, psychiatric, and neuroimaging evaluation

Beh?et's disease (BD) is an idiopathic multisystem disorder. Involvement of CNS occurs in 4-48% of cases. This study was designed to evaluate the prevalence of subclinical neuropsychiatric affection in asymptomatic Egyptian BD patients using psychometric tests and brain imaging with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), also to assess possibly associated clinical predictive variables. Twenty-five BD patients without overt CNS involvement and ten healthy controls matched for age, education, and sex completed a comprehensive neuropsychological battery including Hamilton scales for anxiety and depression and Wechsler memory scale-revised. Disease activity was assessed using Beh?et's Disease Current Activity Form (BDCAF). SPECT was done for all subjects, and 12 patients underwent brain MRI. Compared to controls, 23 (92%) and 24 (96%) patients had anxiety and depression scores respectively above normal range; also, BD patients had significantly lower memory quotient (MQ). SPECT revealed abnormalities in 16/25 (64%), while in 3/12 patients (25%), MRI was abnormal. Subjects with abnormal SPECT had significantly higher ages than those with normal SPECT (P?=?0.02) and were more frequently males (P?=?0.03). No statistically significant differences between cases with normal or abnormal SPECT were found regarding disease duration, frequency of headache, BDCAF, frequency of active eye disease, major vascular involvement, mean Hamilton anxiety and depression scores, and mean MQ. Early diagnosis of neurological involvement in BD is important in reducing or preventing complications. Neuropsychiatric evaluation and HMPAO brain SPECT were found to be useful for detecting subclinical neurological abnormalities in BD patients.     

Epstein-Barr virus and breast cancer: Epidemiological and Molecular study on Egyptian and Iraqi women

Background and purposeThe role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is potentially important for better understanding of breast cancer etiology, early detection and possibly prevention of breast cancer. The aim of the current study is to unravel the association between EBV and primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women).Patients and MethodsThe study was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC), in situ hybridization (ISH) and PCR techniques.ResultsOur gold standard for EBV reactivity in breast cancer cases was positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50 (28%) of Egyptian and Iraqi women; respectively where p = 0.073, compared to 0/20 (0%) of their control groups (p < 0.05). Regarding the association between EBV positivity and tumor grade, there was not any statistical significant difference between EBV presence and tumor grade in both populations where p = 0.860 and p = 0.976 and the calculated rank biserial correlation coefficient was 0.114 and 0.269 for Egyptian and Iraqi women respectively.ConclusionOur findings show that EBV might act as a promoter for the development of PIBC and it might contribute to increased tumor aggressiveness in Egyptian and Iraqi patients.     

Population-based study of ovarian cancer in Côte d'Or: prognostic factors and trends in relative survival rates over the last 20 years

Background  

The aim of this population-based study was to assess independent prognostic factors in ovarian cancer using relative survival (RS) and to investigate changes in RS rates from 1982 to 2005.     

Mortality of oral cavity cancer in Iran

Background: Oral cavity cancer is the eighth most frequent cancer among men in the world. Its incidence varies widely geographically and two-thirds of the incident cases are diagnosed in developing countries. The aim of this study was to present the mortality trends from this cancer for Iranian population during a period of almost a decade, in order to provide update information regarding time trends for this cancer.Methods: We analyzed National death Statistics reported by the Iranian Ministry of Health and Medical Education from 1995 to 2004, stratified by age group, sex, and cause of death. Oral cavity cancer [ICD-10; C00-08] was assessed for annual mortality rates/100,000, overall, by sex and by age group (<15, 15-49 and ≥50 years of age) and age standardized rates (ASR) were calculated. Results: The age standardized mortality rate of oral cavity cancer increased dramatically during these years from 0.09 per 100,000 in 1995 to 0.59 per 100,000 in 2002. However, a sharp decrease was observed from 2002 to 2004. Moreover the mortality of oral cavity cancer was higher for males except from 2000-2002 during which the rate of female’s death was close to male’s. Age specific rates for oral cavity cancer indicated higher mortality rate for older age. Conclusion: In conclusion, this study provides comprehensive projection for burden of death due to oral cavity cancer, indicating that the trend of its mortality was increased in recent decade and then would be leveled off. Whilethe burden of oral cavity cancer in Iran is lower than other Asian countries, further studies are required to establish risk factors or modifiers for this cancer in Iranian population in order to decrease its incidence and mortality.