immunological and histopathological changes of Tramadol, Tramadol/Acetaminophen and Acetaminophen in male Albino rats "Comparative study"

Tramadol is a synthetic opioid analgesic. It is commonly prescribed for moderate to severe pain, becoming abused more popular among teens in most countries. Paracetamol as anti-inflammatory drugs [acetaminophen] [APAP] is widely used as an analgesic and antipyretic agent. Meanwhile, tramadol/acetaminophen [tramacet] is effective in acute or chronic moderate-to-moderately severe pain. In comparative study, the current investigation threw the light on the effect of over doses of tramadol and/or APAP on the immune function and hepatocytes in adult male Sprague-Dawley rats. Treated rats received oral doses of each drug for 15 consecutive days and after last treatment, they kept three days later for withdrawal studies. The rats were divided into four treatment groups, in the first group, rats received saline and used as control. The second, third and fourth groups treated with tramadol [45 mg/kg], tramadol/APAP [45/450 mg/kg], APAP [450 mg/kg] respectively, once a-day at the first week and ending with 90, 90/900, 900 mg/kg at the second week. Rats were sacrificed at the end of the first, second weeks and three days of last treatment. Daily doses of tramadol and /or APAP exposure in rats decreased the cellularity of spleen. Moreover, phagocytic and killing of S. aureus by PMN and macrophage cells caused a highly significant decrease in treated groups. IFN-gamma was reduced in a statistically different treated group of rats. Serum IL-10 was unaffected by any of the treatment regimens but increased only in tramadol/APAP treated rats. Spleen histology exhibited mild pathological alteration with different injures between treated groups. Splenic white pulp accompanied by ill deformed which reflected the reduction of white pulp zones, thickened vasculature in the splenic net work, fibrous trabeculae become prominent feature, where splenic red pulp occupied large areas of the splenic network with predominant edema and megakaryocytes. On the other hand, the effect of tramadol and/or APAP induced DNA alterations of hepatocytes in dose dependent pattern as elucidated by dendrogramatic analysis. Liver histopathological changes of treated groups included vacuolated hepatocytes, dilated sinusoid with proliferated Kupffer cells; atrophied hepatocytes with nuclei reduced in size and darkly stained. Many areas of hepatocytes showed loss of architecture, congested central vein, expanded portal area with edema and inflammatory reaction. It could be concluded that the effect of tramadol/APAP induced anti-inflammatory cytokines than tramadol and APAP alone. Tramadol and/or APAP may display severe pathological consequences of hepatocytes. These hepatic lesions may be caused impairment of the liver function

Role of specific clone of lymphocytes, [CD4[+] and CD8[+]] and the sympathetic activity in pathophysiology of altered immunity in ischemic stroke

Ischemic stroke is one of the major causes of high morbidity and mortality allover the world. The understanding of the pathophysiology of post-ischemic immune response is very limited. Cerebral ischemic stroke affects the normally well-balanced interplay of the 2 super systems: the nervous and the immune system. T-cell lymphocytes, [CD4[-], CD8[-]], may contribute to altered immunity associated with stroke. Increased sympathetic activity during ischemic stroke may have a role in altered lymphocytes function. The present study investigated the contribution of CD4[-] and CD8[-] and the sympathetic activity in altered immunity in ischemic stroke. Determination of CD4[-] and CD8[-] percentage in patient's blood was done by flowcytometry. Evaluation of sympathetic activity done by measuring urinary vanilmandelic acid [VMA] levels by spectrophotometry. The study also correlated the changes of these parameters with specific clinical and diagnostic variables in stroke. The study showed that CD4[-] and CDS percentage were significantly lower [p<0.001], while CD4[-] /CD8[-] ratio was significantly higher [p<0.001] in patients than controls. There was also significantly increased [p<0.001] mean urinary VMA excretion levels [mg/day] in patients compared to control group. Significantly lower CD4[-]% and CD4[-] /CD8[-] ratio and higher CD8[-]% were found in patients with recurrent stroke or history of transient ischemic attacks, progressive strokes and large size of infarction in comparison to other comparable patients. The study indicated that patients with ischemic strokes may have altered immunity and sympathetic over-activity which may be one of the mechanisms by which modulation of immune response can be induced after stroke. This brain-immune interaction after stroke may have protective, destructive, or regenerative effects in the brain, therefore the development of therapeutic strategies is not straightforward, and must take all these factors into consideration

Insulin and glutamic acid decarboxylase antibodies in chronic hepatitis [C] patients with diabetes mellitus

Diabetes mellitus is associated more with HCV chronic liver disease than in the general population and in the other types of chronic liver disease. The increased incidence of diabetes in HCV patients might be related to an autoimmune process produced by the virus or the virus itself has a cytopathic effect on the pancreatic beta clells. The aim of this work was to study the plasma basal insulin level and the seropositivity against glutamic acid decarboxylase [GADA] - an islet cell cytoplasmic antigen. Patients: the study was carried out on 45 patients categorized into 3 equal groups. Group I included 15 diabetic patient with HCV chronic liver disease, Group II included 15 diabetic patients with chronic liver disease which is not related to HCV, Group III included 15 non diabetic patients with HCV chronic liver disease. All patients were selected to be matched regarding age, sex and sevirity of liver disease. The results showed that basal insulin level [22.4 +/- 23.1 micro IU/ml in group I, 21.6 +/- 23.8 micro IU/ml in group II, and 8.8 +/- 6.4 micro IU/ml in group III] were significantly higher in the diabetic patients [GI and GII] compared to the non diabetic [GIII] [P<0.01]. The insulin resistance index as calculated by HOMA equation [9.6 +/- 7.9 in group I, 9.2 +/- 10.3 in group II and 2.4 +/- 1.2 in group III], were also significantly higher in the diabetic groups [p < 0.01]. Seropositivity for [GADA] was 9/15 [60%] of patients of groups I and III and 3/15 [20%] of patients of group II. We concluded that diabetes mellitus associated with HCV chronic liver disease in characterized hyperinsulinaemia and increased insulin resistance. There may be a role of autoimmunity in the pathogenesis of diabetes in HCV chronic liver disease. Follow up of the non diabetic HCV patients with positive GADA for development of diabetes is recommended