Stress mechanism - an emerging role for furosemide

The beneficial effect of furosemide in emergency treatment of acute left ventricular failure starts immediately with the intravenous administration before the occurrence of diuresis. Pulmonary-systemic redistribution of blood volume had been suggested in relieving the left ventricular strain. A central mechanism for furosemide could be suggested because; recent data point to furosemide high specificity and selectivity in antagonizing cerebral GABA neurotransmission and a state of neurohumoral imbalance was suggested in these patients. So this study was conducted to evaluate the potential role of furosemide in the physiological stress mechanism. The effect of a single intraperitoneal dose of furosemide [4mg/kg. of body weight] was tested in a model of emotional stress induced by ultrasound noise, on rat behavioral activity, serum corticosterone level together with the volume of diuresis. Ultrasound noise exposure in a frequency range of 30,000 Hz to 65,000 Hz led to a significant limitation of its activity [freezing reaction]. Serum corticosterone level and behavioral activity are increased significantly in furosemide treated non-stressed and stressed rats compared with both control or stressed group. The increase was marked in furosemide treated-stressed rats. The increase in serum corticosterone and behavioral activity by furosemide in stressed rats indicate a transformation of the stress state from [freezing reaction] to a state of a [defense reaction]. In conclusion; furosemide stimulates the central stress mechanism. This stimulation may be in favor of rapid and potent beneficial effect of furosemide inrecovery of neurohumoral imbalance in stress conditions which probably mediates the pituitary hypothalamic axis

Association of chronic hepatitis C infection and diabetes mellitus.

The aim of the study was to detect a possible aetiological association between chronic hepatitis C virus (HCV) infection and diabetes mellitus (DM). Among the 591 HCV seropositive chronic liver disease (CLD) patients, 150 (25.4%) had associated diabetes mellitus while only 25 of 223 HCV seronegatives (11.2%) were diabetics. The HCV seropositive patients were three times more likely to suffer from diabetes mellitus than those who were HCV seronegative and the results were highly significant (odds ratio = 2.7, CI = 1.7-4.4, P < 0.0001). Liver biopsy showed cirrhosis in 24 out of 53 (45.3%) HCV seropositive diabetics and 9/20 (45%) of the HCV seronegative diabetics. The association between the degree of liver disease and the development of diabetes mellitus did not differ statistically between the two groups. Islet cell antibody (ICA) was present in 44.4% of HCV seropositives compared to 73.3% of seronegative diabetics, while NIDDM showed 40% ICA positivity. Although ICA level was highest in HCV seronegative diabetics, the difference between the various groups was not significant statistically. About 29% of HCV seropositive diabetics were on insulin therapy while only 16% of HCV seronegative diabetics received insulin therapy. HCV seropositives were about 2 times more prone to require insulin therapy than HCV seronegatives (odds ratio = 2.0, CI = 1.2-5.7, P = 0.010). We conclude that chronic hepatitis C patients in Egypt are three times more likely to develop DM than HCV seronegative patients. Pancreatic beta -cells might be an extrahepatic target of HCV.

Does schistosomiasis play a role in the high sero prevalence of HCV antibody among Egyptians?

Many studies have demonstrated a very high prevalence of HCV antibodies among blood donors (BD) and chronic liver disease (CLD) patients in Egypt. This high prevalence might be attributed to cross reactivity between HCV antibodies and schistosome antibodies. We decided to study the association and cross serology between the presence of anti-HCV and Schistosomal infection among BD and CLD patients. Sera of blood donors and CLD patients were tested for anti-HCV by second generation ELISA. Antibodies to Schistosoma species were quantified by IHA test. Two tailed z score was used to detect significant difference. To test for cross reactivity between the two antibodies 20 BD and 20 CLD patients positive for both HCV-antibody and schistosome antibody were taken as controls. Another 20 samples also served as a control group; 10 of them seropositive for HCV only and 10 positive for IHA for schistosomiasis alone. All were subjected to: 1) RIBA-2 confirmatory test 2) Adsorption of schistosome antibodies using 100 microgram schistosome antigens per 100 microliters serum 3) Both HCV-ELISA-2 and RIBA-2 were checked after adsorption. The titre of schistosome antibodies in positive sera ranged from 1:128 to 1:1536. HCV seroprevalence was more pronounced among antischistosomal positive sera. This was seen in both BD and CLD patients where antischistosomal positive sera were at double risk to show positive HCV antibody. After adsorption of schistosome antibody, there was no change in reactivity of both ELISA-2 and RIBA-2. We conclude that HCV antibodies were significantly higher in schistosomal antibody positive Egyptians, there was no cross reactivity between the two antibodies and the high prevalence could be due to HCV transmission during anti-bilharzial parenteral therapy or due to depressed cell mediated immunity associated with schistosomal infection.