Postprandial platelet depleted plasma 5-hydroxytrypamine concentration in symptomatic female with diarrhea predominant irritable bowel syndrome

Serotonin [5-HT] may play an important role in the regulation of colonic motility in humans. However, Meal ingestion is often associated with exacerbation of gastrointestinal symptoms in subjects with irritable bowel syndrome [IBS]. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome [IBS]. To assess plasma serotonin [5-HT], 5-hydroxyindole acetic acid [5-HIAA] concentrations, 5-HT turnover, platelet 5-HT stores, and any relationship to symptomatology. In addition, to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. After an overnight fast, 20 healthy female volunteers [aged 21- 46 years] [mean 29.3], and 39 female subjects with diarrhea predominant irritable bowel syndrome [d-IBS] [aged 20-48 years] [mean 31.4], were given a standard carbohydrate meal [457 Kcal]. Platelet depleted plasma 5-HT, and 5-HIAA concentrations for two hours [60 minute intervals] under fasting conditions, and then for a further four hours [30 minute intervals] after standard carbohydrate meal were assessed, together with fasting platelet 5- HT concentrations. IBS symptomatology, in particular abdominal pain and bloating, and urgency to defecate were assessed throughout the study. Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea-predominant and from subjects with normal bowel habit by endoscopic biopsy, the tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection. When related to fasting level, there was no statistically significant difference in postprandial plasma 5-HT concentrations between d-IBS and healthy subjects. However, when fasting levels were not taken into consideration, d-IBS subjects exhibited higher postprandial plasma 5-HT concentrations compared with healthy subjects [p = 0.040]. Furthermore, d-IBS subjects who exhibited postprandial symptomatology had higher levels of postprandial plasma 5-HT, whether assessed with respect to fasting baseline levels [p = 0.065] or not [p = 0.046], compared with dIBS subjects who did not report postprandial symptomatology. This appeared to be associated with a concomitant increase in plasma 5-HIAA [p = 0.162] but reduction in turnover [0.057]. Also, d-IBS subjects had higher platelet concentrations of 5-HT than healthy subjects [p = 0.009]. The mean mucosal 5-HT concentrations obtained from the rectum regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with d-IBS were significantly [p = <0.05] lower than those obtained from the control subjects. No significant difference were observed in 5-HIAA concentrations among the two groups. These data suggest that postprandial symptomatology may be associated with increased platelet plasma 5-HT concentrations in female subjects with d-IBS. The increased release of 5-HT into plasma leads to depletion of mucosal 5-HT in subjects with d-IBS. The presence of increased platelet stores of 5-HT may act as a useful marker for the diagnosis and management of d-IBS

Evaluation of antibodies to 60s ribosomal phosphoproteins in systemic lupus erythematosus

Despite their recognition in systemic lupus erythematosus [SLE] patients more than 30 years ago, the prevalence and disease associations of anti-ribosomal P[anti-P] antibodies are controversial. We attempted in this study to evaluate the prevalence, the clinical significance and the pathogenesity of anti-ribosomal antibodies in SLE patients. Our study included 82 patients with SLE [71 females and 11 males] with age ranging from 17 to 50 years [27.6 +/- 9.2] in addition to twenty age and sex matched healthy individuals as a control group. Routine investigations, together with urine microscopy, 24-hour urinary protein quantitation, creatinine clearance, liver function tests and serum C3 level were performed. Renal biopsy was performed for most patients with lupus nephritis. Brain Computed tomography [C.T], Electroencephalogram [EEG] and Magnetic Resonance Immaging [MRI] were done for patients with neuropsychiatric lupus. The clinical activity of the disease was assessed by the SLE disease activity index [SLEDAI] after full clinical examination including rheumatological examination. Immunologic investigations included: 1] determination of anti-P antibodies by an enzyme linked immunosorbent assay [ELISA] method using a highly purified COOH terminal 22 amino acid peptide as an antigen. 2] indirect immunofluoresent technique for the detection of antideoxy ribonucleic acid [dsDNA], anti-smooth muscle antibodies [ASA] and anti-mitochondrial antibodies [AMA]. 3] ELISA methods for the detection of anticardiolipin antibodies [ACA] IgG and IgM, hepatitis C virus antibodies [HCV] IgG and hepatitis B surface antigen [HBsAg]. Anti-P antibodies were positive in 22/82 [26.8%] of patients with SLE and in none of the normal control subjects. Accordingly we classified our patients into two groups: Group I with positive anti-P antibodies [22 patients] and group II with negative anti-P antibodies [60 patients]. Hepatitis [which could be attributed to SLE and not to other causes since they were negative for ASA, AMA, HCV and HBV] was reported in 21/82 [25.6%] of our SLE patients. Fifteen of them were from the anti-P positive group [15/22, 68.1%] and 6 were from the anti-P negative group [6/60,10%]. This difference was statistically highly significant [p<0.001]. Regarding the incidence of lupus nephritis, it was [18/22, 81.8%] in the anti-P positive group, while in the anti-P negative group it was [24/60, 40%], the difference was statistically significant [p<0.001]. There was no statistically significant difference between anti-P positive and anti-P negative patients with regard to the presence of anti-ds DNA antibodies. Lupus psychosis was reported in 12/22 [54.5%] of anti-P positive patients [group I] and in 6/60 [10%] of anti-P negative patients [group 11], the difference was statistically highly significant [p<0.001]. The level of ACA in the sera of our patients was correlated significantly with the level of anti-P antibodies [r = 0.573 and p<0.001 for IgG ACA and r = 0.773 and p<0.001 for IgM ACA]. Clinical observations revealed that the presence of anti-P antibodies was significantly correlated with disease severity determined by systemic lupus erythematosus disease activity index [SLEDAI]. The SLEDAI score was significantly elevated with a mean of 26.9 +/- 2.6 in anti-P positive patients [group I] and a mean of 17.2 +/- 1.6 in the anti-P negative patients [group II] [p<0.001]. The level of C3 was significantly reduced in anti-P positive patients when compared with anti-P negative patients [p<0.001]. We concluded that, although anti-P antibodies were present in a small percentage of SLE patients, yet they were significantly associated with more aggressive disease, with increased incidence of hepatic, renal and central nervous system [CNS] involvements. Thus, the determination of anti-P antibodies may be one of the useful prognostic tools in identifying a subset of SLE patients with more severe disease associations and early major organe affections, that necessitate close clinical observations and frequent follow up visits. Large scale prospective study can better illuminate the relationship of anti-P antibodies to clinical disease expression, especially hepatitis and CNS involvement