The role of CK7, Ki-67, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates

The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.     

Phase II Trial: Undifferentiated Versus Differentiated Autologous Mesenchymal Stem Cells Transplantation in Egyptian Patients with HCV Induced Liver Cirrhosis

The study was aimed to evaluate the effect of autologous transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis C virus infection. Twenty-five patients with Child C liver cirrhosis, MELD score >12 were included. They were divided into 2 groups. Group I, the MSCs group (n=15), this group was subdivided into two subgroups: Ia & Ib (undifferentiated and differentiated respectively). Group II (control group; n=10) involved patients with cirrhotic liver under conventional supportive treatment. Ninety ml BM was aspirated from the iliac bone for separation of MSCs. Surface expression of CD271, CD29 and CD34 were analyzed using flowcytometry. Hepatogenesis was assessed by immunohistochemical expression of OV6, AFP and albumin. Finally approximately 1 million MSCs/Kg were suspended in saline and were placed in blood bag and injected slowly intravenously over 15 min at a rate of 5 drops/min in one session. Follow up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin levels, decline of elevated bilirubin and MELD score in MSCs group. Statistical comparisons between the two subgroups (group Ia & Ib) did not merit any significant difference regarding clinical and laboratory findings. In conclusion: Bone marrow MSCs transplantation either undifferentiated or differentiated can be used as a potential treatment for liver cirrhosis.     

Nebulized hypertonic saline to prevent ventilator associated pneumonia in premature infants,a randomized trial

Background/objectives: Ventilator associated pneumonia (VAP) is a leading cause of death. Nebulized hypertonic saline solution (HSS) has been used to improve pulmonary clearance and reduce infection in intubated patients. This study examines whether nebulized HSS may reduce VAP in intubated premature infants.

Methods: We analyzed results of 100 intubated premature infants who completed the study. Infants were divided into: (a) the “Control” group, where VAP prevention protocol was implemented and (b) the “Intervention” group, where nebulized HSS twice daily was added to the package of care. Clinical, radiologic, and laboratory evidence of VAP, endotracheal aspirate and blood cultures, and days on mechanical ventilation were compared between groups.

Results: VAP occurred in 18% in the intervention group compared to 52% in the control group, relative risk 0.35 (CI:0.18–0.66, p?=?.001). VAP incidence density was 16/1000 patient-ventilator days in intervention group versus 30/1000 in control group. There was a significant reduction in the days of mechanical ventilation in the intervention group (10.7?±?8.6 and 16.9?±?3.4, p?Conclusions: Nebulized HSS may help preserving lung clearance mechanisms and therefore reduce VAP in premature infants. Multi center, double blinded, randomized, controlled, trial is needed to confirm safety and efficacy of such intervention.     

Aluminium-induced deterioration in reproductive performance and seminal plasma biochemistry of male rabbits: protective role of ascorbic acid

Aluminium (Al) has been proposed as an environmental factor that may contribute to some diseases, affect several enzymes and other biomolecules and induced free radical-mediated cytotoxicity. Also, Al induced reproductive toxicity and exerted a significant adverse effect on the steroidogenesis. The antioxidant ascorbic acid (AA) plays an important role in various physiological processes in the body including detoxification of different toxic materials. Therefore, the present investigation aimed to elucidate possible protective effects of AA in alleviating the toxicity of aluminium chloride (AlCl3) on reproductive performance, lipid peroxidation and enzyme activities in seminal plasma of male New Zealand white rabbits. Six rabbits per group were assigned to one of four treatment groups: 0 mg AA and 0 mg AlCl3 /kg body weight (BW) (control); 40 mg AA/kg BW; 34 mg AlCl3 /kg BW; 34 mg AlCl3 plus 40 mg AA/kg BW. Rabbits were orally administered their respective doses every other day for 16 weeks. Results obtained showed that AlCl3 significantly (P<0.05) decreased libido (by increasing the reaction time), ejaculate volume, sperm concentration, total sperm output, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), total functional sperm fraction (TFSF), normal and live sperm and semen initial fructose. While initial hydrogen ion concentration (pH) and dead and abnormal sperm were increased (P<0.05). Live body weight (LBW), feed intake (FI) and relative weights of testes (RTW) and epididymis (REW) were significantly (P<0.05) decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly (P<0.05) increased in seminal plasma of rabbits treated with AlCl3 compared with control. While, activities of glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (AcP) were significantly (P<0.05) decreased. Ascorbic acid alone significantly increased LBW, FI, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of free radicals. Also, the present study showed that ascorbic acid might be effective in the protection of aluminium-induced reproductive toxicity. It was suggested that AlCl3 exerted a significant adverse effect on reproductive performance of male rabbits. Furthermore, AA could be able to antagonize the toxic effects of AlCl3 and improved semen quality of male rabbit.     

Genetic variation in BCL-2 and response to interferon in hepatitis C virus type 4 patients

The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. BCL-2 gene polymorphism at codon 43 (127G/A) has been found to be a reliable and sensitive marker for the prediction of response to interferon therapy during viral infections. This study examined the correlation of BCL-2 gene polymorphism with the response to treatment with pegylated-IFN-alfa2b and ribavirin. Eighty patients with type 4 HCV and 40 healthy volunteers as controls were enrolled in a prospective study. Quantification of HCV-RNA by real-time PCR was performed for every patient, and gene polymorphism of BCL-2 (ala 43 Thr) was performed for all patients and controls. There was a statistically significant difference between non-responder patients and control group as regards the 43Thr genotype and allele (P<0.05). Also, there was a statistically significant difference between responders and non-responders (P<0.05) as regards 43Thr genotype and alleles. We conclude that BCL-2 gene polymorphism at codon 43 (127G/A) is a new biological marker to potentially identify responders and non-responders of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN in combination with ribavirin.     

Beneficial effects of pioglitazone against cardiovascular injury are enhanced by combination with aliskiren in a rat model of diabetic nephropathy

Objectives Aliskiren is the first in a new class of orally active direct renin inhibitors, approved for the treatment of hypertension. However, the efficacy of aliskiren in diabetic cardiovascular complications remains to be defined. This study aimed to test the hypothesis that aliskiren may enhance the beneficial effects of pioglitazone against cardiovascular injury associated with diabetic nephropathy. Methods Diabetic nephropathy was induced in rats by unilateral nephrectomy followed by streptozotocin injection. Diabetic nephropathic rats were orally given vehicle, pioglitazone, aliskiren, or combined pioglitazone and aliskiren for four weeks to compare their effects on cardiovascular injury, particularly myocardial fibrosis. Key findings Pioglitazone treatment significantly attenuated cardiac lipid peroxidation, oxidative injury and myocardial fibrosis in diabetic nephropathic rats. This was associated with up‐regulation of transforming growth factor‐β1 and matrix metalloproteinase‐2 genes, along with down‐regulation of tissue inhibitor of metalloproteinase‐2 gene in cardiac tissue. The combination of aliskiren with pioglitazone exerted greater beneficial effect than monotherapy with either drug, on all the aforementioned parameters. Conclusions Our findings suggested that aliskiren enhanced the protective effects of pioglitazone against myocardial fibrosis, in experimental diabetic nephropathy. Thus, the combination of aliskiren and pioglitazone may be a potential therapeutic strategy for cardiovascular injury associated with diabetic nephropathy.