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Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes β-hexosaminidase (β-NAG) and β-glucuronidase (β-GLU) increased significantly after 24 hrs, while the level of β-GLU returned to normal after 48 hrs, but the activity of β-NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of β-NAG, but did not influence the histological changes. [ABSTRACT FROM AUTHOR]

Comments on published case of a patient with suspected ischemic colitis who received tegaserod for irritable bowel syndrome (IBS) with constipation. Data on the safety and tolerability of the drug; Review of clinical experience with the drug; Susceptibility of patients with IBS to ischemic colitis.

Background: Medical treatments for gastro-oesophageal reflux disease (GERD) vary in their ability to completely resolve heartburn and other symptoms. Although GERD reduces health-related quality of life (HRQL) little is known about the relationship between resolution of heartburn symptoms with medical therapy and HRQL. We evaluated the association between complete resolution of heartburn symptoms and functioning and well-being in three samples of patients with GERD., Methods: We analysed baseline and follow-up assessments of heartburn symptoms and HRQL scores from three clinical trials (total n=1351) comparing omeprazole and ranitidine for acute symptomatic treatment of GERD. Heartburn symptoms were measured using patient diaries and/or patient self-report. HRQL was assessed using the Psychological General Well-Being Index (PGWB) in all three clinical trials and the SF-36 Health Survey in two clinical trials. Resolution of heartburn symptoms was defined as no heartburn reported during the assessment period., Results: We observed statistically significant differences favouring patients with no heartburn symptoms on the PGWB total score (P=0.018 to P < 0.0001) and anxiety (P=0.002 to P < 0.0001), general health (P=0.05 to P < 0. 0001), positive well-being (P=0.028 to P < 0.0001) and vitality (P=0. 05 to P < 0.0001) sub-scale scores at 4-14 weeks. Patients with no heartburn reported better SF-36 pain (P=0.005 to P < 0.0001) and general health perceptions (P=0.032 to P < 0.0001) compared with patients still experiencing heartburn symptoms at 4-24 weeks. SF-36 physical component summary scores were significantly better in patients with no heartburn symptoms compared with patients with heartburn symptoms at 4-24 weeks (P=0.013 to P=0.009), while mental component summary scores were only significantly different at 24 weeks (P=0.0005) in one of the two studies where the SF-36 was utilized., Conclusions: Complete resolution of heartburn symptoms was consistently associated with improvement in HRQL; the greatest impact was observed on measures of psychological well-being and physical functioning and well-being. Effective treatment of GERD that completely resolves heartburn results in clinically significant improvement in patient HRQL.