ABSTRACT
Background: Depression is one of the most common affective disorders. Tri-Cyclic Antidepressants [TCA] and Selective serotonin re-uptake inhibitors [SSRIs] were the most common agents used in treatment of depression. There is now evidence that depression is associated with overproduction of pro-inflammatory cytokines including tumor necrosis factor-alpha [TNF-alpha] and the effectiveness of antidepressants is related to suppression of their production with consequent improvement of depression symptoms
Objectives of this Study: This study was designed to compare between acute toxicity with TCA and SSRIs and to detect their effect on the TNF-alpha m-RNA expression, trying to establish a new and easy parameter to help in diagnosis and prognosis of the cases
Subjects and Methods: This study included 40 acutely poisoned patients of both sex and different ages admitted to the poison control center [PCC], Ain Shams University. These patients were classified into: Group I: it included 13 patients acutely intoxicated with one of SSRIs, Group II: it included 27 patients complaining of acute intoxication with one of TCA. Group III: Control group, which is subdivided into Group IIIa: including 10 apparently healthy volunteers and Group IIIb: including 10 depressed patients with no history of treatment. Every subject was subjected to history taking and clinical examination. Aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were estimated. Quantitative TNF-alpha m-RNA expression in peripheral blood mononuclear cells was performed
Results: Most of the cases in the 2 studied groups [SSRIs and TCA] were females, teenagers or young adults and were acutely intoxicated due to suicidal attempts with no significant difference between the two groups. There was a significant difference between the TNF-alpha levels in patients acutely poisoned with either SSRIs or TCA with no history of depression or its treatment and the normal healthy volunteers as a control group [IIIa]. On the other hand, there was a highly significant difference between the patients acutely intoxicated with SSRIs or TCA with history of depression and on treatment and the depressed patients with no treatment as a control group [IIIb]. The study also detected that there was a significant difference between the 2 studied groups [IandII] as regards cardiovascular ,neurological signs and symptoms ,AST and ALT levels
In conclusion: TCA toxicity is much more dangerous than SSRIs toxicity. The toxicity by both groups of drugs leads to a decrease in the TNF-alpha level in the blood either in normal or depressed cases. Based on this, TNF-alpha can be used in diagnosis but not prognosis of toxicity with antidepressants
ABSTRACT
Increased expression of inducible nitric oxide synthase [iNOS] has been observed in patients with chronic inflammatory diseases of the gastrointestinal tract leading to sustained production of nitric oxide [NO] which may induce DNA damage. Since Helicobacter pylori [H. pylori] infection produces a state of chronic immunostimmulation in the gastric epithelium and a causal relationship between H. pylori CagA+ strains infection and gastric cancer has been suggested, therefore, our aim was to evaluate the significance of iNOS expression in gastric lesions induced by H. pylori CagA+ strains with correlation to the encountered endoscopic and pathological diagnoses. Eighty four dyspeptic patients underwent endoscopic examination. Four antral gastric biopsies were obtained for detection of H. pylori by histopathological assessment [Giemsa staining], urease test and gene expression of H. pylori using PCR assay. Immunohistochemical staining for iNOS expression and quantitative detection of anti-CagA antibodies were performed. It was found that H. pylori infection was detected in 64.3%, CagA seropositivity in 54.8% and iNOS expression in 61.9%. Anti-CagA antibodies seropositivity and iNOS immunoexpression were significantly related to H. pylori infection. The positive rates of iNOS immunostaining increased with the lesion progression from chronic superficial gastritis to chronic atrophic gastritis to intestinal metaplasia [45.2%, 87.5% and 92.8% respectively]. Positive immunostaining rates of iNOS correlated significantly with H.pylori Cag A seropositivity with respect to both endoscopic and pathologic diagnoses. In conclusion, CagA+ H. pylori strains are associated with enhanced immunoexpression of iNOS in H. pylori-related gastric diseases, therefore they might contribute as risk cofactors that conduces to gastric carcinogenesis. Given the high prevalence of H. pylori gastric diseases and frequent performance level of endoscopic gastric examinations among Egyptian patients, prompt identification of gastric infections caused by H. pylori harboring Cag A virulence factor is necessary for the early eradication of infection before the development of pre-neoplastic lesions