Study of apoptosis inducing Fas receptors on T and B lymphocytes, soluble Fas and caspase 3 in type 1 diabetes mellitus

Aim: The aim of this work was designed to assess the expression of Fas receptors on T and B lymphocytes from patients with type 1 diabetes mellitus at different stages of the disease and to analyse the role of the soluble isoform of Fas and caspase-3 in Fas mediated apoptosis of T and B lymphocytes. Subjects and this study was carried on 21 type 1 diabetic patients divided into two groups: newly diagnosed [ND] and longstanding [LS], and 10 normal subjects as control group. All patients were subjected to thorough history taking, clinical examination, and laboratory investigations [fasting blood glucose and glycated haemoglobin], Immunofluorescence staining and flow cytometry analysis for Fas receptors on T and B -lymphocytes was done. Soluble isoform of Fas [S-Fas] was measured in the plasma by Elisa, and caspase-3 activity was assessed by colorimetric chemical method. Fas receptors: expression on T lymphocytes was significantly decreased among ND diabatic patients than LS and normal controls [P<0.001 and P < 0.049] and the percentage of T cells expressing Fas receptors was significantly increased in ND diabetics versus LS and controls [P = 0.000 and P= 0.000]. The soluble isoform of Fas was significantly increased in ND diabetic patients as compared to LS and control groups [P =0.000 and P< 0.015]. There was a positive correlation [r=0.750, P= 0.000] between Fas receptor expression as mean fluorescence intensity ratio of T cells and that of B cells and a negative correlation with s-Fas [r= 0.750, P= 0.000 and r= -0.540, P=0.004 and r= -0.573, P=0.002, respectively] in diabetic patients. Conclusions: Defective apoptosis of peripheral lymphocytes is well documented and clearly expressed both at the cell membrane Fas receptors and plasma s-Fas levels in ND type 1 diabetic patients. So, it is likely that defective Fas-mediated apoptosis of peripheral lymphocytes may contribute partly to loss of tolerance seen in type 1 diabetes mellitus

Plasma Homocysteine: s marker for coronary atherosclerosis and endothelial dysfunction in rheumatiod arthritis?

The aim of the present work is to assess total homocysteine level [tHcy] in rheumatoid arthritis [RA] patients and its relation to the presence of coronary atherosclerosis and endothelial dysfunction. Subjects and 20 female patients with rheumatoid arthritis and 10 healthy control subjects matched for age and sex were subjected to estimation of total plasma homocysteine concentration by high performance liquid chromatography and fluroscent detection, and von Willebrand factor [vWF], a reliable marker of endothelial cell dysfunction using ELISA technique. Intimal-medial thickness, peak systolic and diastolic velocities in the common carotid artery were measured using Duplex ultrasound, and resistance index was calculated. The results revealed significant increase in total homocysteine level in rheumatoid patients as compared to normal controls [31.33 +/- 14.4 versus 12.5 +/- 2.08, P<0.05] with no significant difference between patients with ischaemic heart disease and without. Also, von Willebr and factor was significantly higher in patients as compared to controls [2.01 +/- 0.5 versus 1.5 +/- 0.3, P<0.05] with positive correlation between homocysteine level and vWF [r=0.881]. Duplex ultrasound evaluation demonstrated mean intima-media thickness wich was significantly greater in RA patients as compared to the control group [0.63 +/- 0.1 versus 0.3+0.6, P<0.05] and positively associated with [tHcy] level [r=0.836310] with high resistance index [62.6 +/- 19.48]. Conclusions: RA patients have fasting hyperhomocysteinemia, which may be a marker for premature atherosclerosis and endothelial dysfunction. Further studies are needed to determine the clinical impact of homocysteine lowering therapy

Osteoporotic changes in Egyptian cirrhotic patients

Aim: Hepatic osteodystrophy occurs in most patients with chronic liver disease. Subjects and In this study, bone density, measured by dual energy X-ray absorptiometry [DEXA], and some biochemical markers of bone turnover were studied in 30 Egyptian schistosomal patients classified equally into 3 groups according to the Child-Pugh score of severity of liver disease. Patients showed significant reduction of BMD in both lumbar spine and femoral neck [LS: -2.87 +/- 1.39; FN: -0.54 +/- 1.13, p< 0.001]. Osteoporosis was found in 56.7% of patients. Urinary D-Pyr/cr, as a marker of bone resorption, showed marked significant increase in Child B and C patients [p<0.001], while serum B-AP and serum PICP, as markers of bone formation, showed less changes. Serum B-AP was significantly increased in the patient group [p<0.05], while serum PICP was insignificantly decreased in patients as compared to controls. The rate of bone loss, determined by the ratio of urinary D-Pyr/cr to PICP, was increased in Child A, B, and C patients. Serum testosterone was significantly decreased in both Child B and C patients and was markedly decreased in the whole patient group [p<0.001]. Conclusions: These results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and its risk increases with the severity of liver disease. It also provides bone biomarkers as useful alternatives to bone biopsy in evaluating hepatic bone changes

Volume homeostasis in schistosomal patients with and without renal involvement

The aim of this study was studying some humoral and renal mechanisms controlling volume homeostasis during volume expansion and volume depletion among schistosomal patients with and without renal involvement. The subjects included in this study were ten non ascitic schistosomal patients [group A], another ten non ascitic proteinuric schistosomal patients [group B], ten control subjects [group C]. All groups were subjected to full history taking, clinical examination and investigations [stool analysis or rectal snip biopsy, urine analysis and urine protein estimation, renal function tests, liver function tests, hepatitis viral markers and percutaneous renal biopsy for nephrotic patients]. Experimental protocol included two studies: study I: this included infusion of isotonic saline [0.9%] in a dose of 40 ml/kg body weight over 30 minutes for acute volume expansion. Study 2: this included the administration of furosemide in a dose of 0.75 mg/kg body weight during one minute. The change in plasma volume after each study was calculated. Estimation of at rial natriuretic peptide [ANP] by radioimmunoassay basally and 1 hour after the study, plasma renin activity [PRA] and plasma aldosterone [PA] were done pre-study as well as, 1,2, and 3 hours post study. Fractional excretion of sodium, urinary sodium excretion rate, free water clearance as well as urinary flow rate were calculated before and after the study. Serum proteins and serum albumin were significantly lower in the schistosomal proteinuric group [group B]. Prothrombin activity showed a significant decrease in both groups A and B. All subjects of the three groups were negative for the studied viral markers. All nephrotic patients [group B] were biopsied and revealed membrano-proliferative type of glomerulonephritis. The percentage increase and decrease in plasma volume after volume expansion and depletion were comparable in the three studied groups with no significant difference. The basal ANP showed no significant difference between the three groups, it showed a significant rise especially in group B after volume expansion and a significant decline after volume depletion in the three groups. Schistosomal proteinuric patients [group B] showed incomplete suppression of PRA after volume expansion, there was a sustained rise in PRA and PA in schistosomal patients [group A] after volume depletion. The basal PA was significantly higher in schistosomal patients [group A] than the controls, it showed a significant decrease after volume expansion in the three studied groups. Fractional excretion of sodium showed a significant rise after volume expansion in the three studied groups, there was a significantly lower value in the first hour interval in all schistosomal patients [group A and B] than that of the control group[C], after volume depletion it showed a significant rise in the first and second hours only in all schistosomal patients [A and B]. Urinary sodium excretion rate showed a significant increase after volume expansion in the three studied groups, but the natriuresis was found to be impaired after the first hour in all schistosomal patients [group A and B] in comparison to the control subjects [group C]. After volume depletion,urinary sodium excretion rate showed a significant increase in the three studied groups. All schistosomal patients [group A and B] showed blunted natriuretic and diuretic response to furosemide when compared to the control group [C]. Free water clearance after volume expansion showed a significant rise in the first hour interval in group A, in the first and second hour interval in B and in the three hours intervals in C. After volume depletion there was no significant difference in the basal, first,second, and third hour interval values between the three groups. Urine flow rate increased significantly after volume expansion and diuretics in the three groups. All schistosomal patients [group A and B] showed significant lower values in the first and second hour after both volume expansion and depletion than the controls. ANP was involved in the regulation of blood volume in schistosomal patients with and without proteinuria. The high basal aldosterone levels in schistosomal patients may be related to impaired metabolic degradation rather than increased production. There was blunted natriuresis and diuresis in schistosomal patients early in the preascitic stage, this may be due to resistance to the properly released ANP. This resistance was related neither to its hypotensive action nor to hyperaldosteronism.The impaired urinary sodium excretion may be related to the increased tubular reabsorption. Schistosomal proteinuric patients tended also to retain sodium inspite of the proper hormonal response, so renal resistance may be a cause. Schistosomal patients tended to retain water and the ability to excrete free water was better in schistosomal proteinuric There was a state of diuretic resistance to furosemide in schistosomal patients with and without proteinuria