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1.
Bulletin of Alexandria Faculty of Medicine. 2009; 45 (1): 75-84
in English | IMEMR | ID: emr-100736

ABSTRACT

Systemic lupus erythenwtosus [SLE] is a chronic multisystem autoimmune disease. Renal involvement [lupus nephritis; LN] is a frequent and potentially serious complication that worsens morbidity and mortality. LN is a chronic disease with remissions and relapses, and this is important to predict aiming for optimal management. However, a consistent approach still has not been adopted. To study serum and urinary' soluble vascular cell adhesion molecule-I [sVCAM-1] levels in patients with lupus nephr itis and their correlation with the disease activity, laboratory data and renal pathology. Twenty three patients with lupus nephritis and twenty age, sex and ethnic matched healthy controls were subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, eiythrocyte sedimentation rate [ESR], renal functions, urine analysis, 24-hour urinary protein excretion, liver functions, serum antinuclear antibody [ANA], anti-double stranded deoxyribonucleic acid [anti-dsDNA], serum and urinaly soluble VCAM-1 [sVCAM-1] and other necessary investigations. Percutaneous renal biopsy, with histopathological assessment and determination of activity and chronicity indices, was done for all patients. LN patients had a statistically sign[ficantly higher serum [S] and urinary sVCAM-1, S. ANA, S. antidsDNA, ESR, blood urea, S.creatinine, S.uric acid, 24-hour urinary protein excretion and S. alanine and aspartate aminotransferases, and a statistically significantly lower hemoglobin concentration, S. albumin and creatinine clearance tjian healthy controls. Renal biopsy assessment showed World Health Organization [WHO] class 11 LN in 3 patients, class iii in 4 patients, class IV in 13 patients and class V in 3 patients. S. sVCAM-1 was statistically significantly higher in classes III, IV and V LN than controls and in class IV LN than class II. Urinary sVCAM-1 was statistically signficantly higher in classes II, III, IV and V LN than controls and in classes III and IV LN than class II. Anti-dsDNA was statistically significantly higher in classes III and IV LN than controls, with no statistically significant differences in between the WHO classes. S. and urinary sVCAM-1 showed a statistically wreianon with the total SLEDAI score, pathologic activity index and urinary protein excretion, with a significantly positive correlation between S. and urinary sVCAM-1. A significantly negative correlation was present between S. sVCAM-1 and hemoglobin concentration, and between urinary sVCAM-1 and S. albumin. As regards anti-dsDNA, no statistically significant correlations were observed. In patients with LN, serum and urinary sVCAM-1 are positively correlated with the total SLEDAI score, pathologic activity index and urinary protein excretion. Measurement of their levels, specially urinary sVCAM-1, seems to be valuable in evaluating LNpatients. Further studies are recommended to assess the role of repeated measurements. Whether a blockade of soluble VCAM-1 could have a therapeutic implication in LN remains to be investigated


Subject(s)
Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/urine , Albuminuria , Disease Progression
2.
Bulletin of Alexandria Faculty of Medicine. 2009; 45 (1): 85-94
in English | IMEMR | ID: emr-100737

ABSTRACT

Despite advances in the knowledge of the molecular virology of hepatitis C virus [HCV], the mechanisms of hepatocellular injury in HCV infection are not completely understood. The available reports are in favor of a destructive mechanism mediated by the host immune system rather than a direct cytopathic effect of the virus. Some viral infections influence the susceptibility of peripheral blood mononuclear cells [PBMC] to apoprosis. This could lead to insufficient antiviral immune response, persistent viral infection and disease progression. To evaluate the expression of apoptotic markers Bcl-2 and Bax in PBMC in chronic HCV patients. The study included three groups; group 1. Fifteen chronic HCV patients with biopsy-proven liver cirrhosis and ascites; among this group, five patients had cryoglobulinemia [group la] and the remaining ten patients had no cryoglobulinemia; group lb. Group 2: Ffteen chronic HCV patients without any suspected evidence of liver cirrhosis and group 3: Fifteen healthy subjects as a control group. All groups were age and sex matched and subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, liver and renal functions, Hepatitis B suiface antigen, anti-HCV antibodies, serum cryoglobulins, detection of apoptotic markers Bcl-2 and Box in peripheral blood lymphocytes, other necessary tests and in addition serum HCV RNA levels in the patient groups, by quantitative polymerase chain reaction [PCR] assay, and peritonealfluid analysis in group 1 patients. Group 1 chronic HCV patients [with cirrhosis and ascites] had a statistically significantly low Bcl-2 percentage expression in peripheral blood lymphocytes, a significantly high Bax expression and a significantly decreased Bcl-2/Bax ratio compared than healthy controls, with a statistically significant difference between group la [cryoglobulinemic] and group lb [non-cryoglobulinemic]. Group 2 patients had a statistically significantly increased Bcl-2 percentage expression, a signcantly decreased Bax expression and a significantly increased Bcl-2/Bax ratio than controls. In chronic hepatitis C virus patients [group 1 and 2] Bcl-2 expression showed a statistically significant positive correlation with S. albumin, prothrombin activity, ALT and the Bcl-2/Bax ratio and a significantly negative correlation with S. total blirubin, blood urea and the Bax expression. Bax expression showed a statistically significant positive correlation with S. total blirubin, blood urea and S. creatinine and a significantly negative correlation with S. albumin, prothromhin activity, ALT and the Bcl-2/Bcvc ratio. Bcl-2/Bax ratio showed a statistically significant positive correlation with S. albumin, prothrombin activity and ALT and a significantly negative correlation with S. total blirubin, blood urea and S. creatinine. Chronic HCV patients exhibit a dysregulation of apoptosis, in the form of a down regulation of Bcl-2 expression together with an increasd Bax expression and, a decreased Bcl-2/Bax ratio in peripheral blood lymphocytes, with the disease pro gression. This provides an insight into the pathogenesis of chronic HCV infection and may open new avenues in the management of the disease


Subject(s)
Humans , Male , Female , Apoptosis , Genes, bcl-2 , /blood , Polymerase Chain Reaction , Liver Function Tests
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