The Italian journal of gastroenterology最新文献

The observations reported in this paper have led to the formulation of a new hypothesis concerning the action of NSAIDs updating the concept first put forward in the early 70's. The new paradigm is that COX 1, a constitutive enzyme is thought to be a housekeeping protein, and to be important in generating prostaglandins necessary for physiological purposes, amongst which may be suppression of gastric acid secretion. In contrast, the induced COX 2 enzyme appears mainly after cell injury and inflammation and is responsible for generating the prostaglandins which mediate inflammatory episodes. In this model, inhibition of COX 1 is thought to produce the undesirable side effects of NSAID therapy, whereas inhibition of COX 2 is thought to be responsible for the anti-inflammatory effects. COX 2, therefore, appears to be the enzyme that should be targeted in anti-inflammatory drug therapy. By designing or screening for specific COX 2 inhibitors, it should be possible to develop drugs which are at least as effective anti-inflammatory agents as the current NSAIDs, but that are much safer in terms of gastrointestinal and other side effects. Early preclinical experience with highly selective inhibitors of COX 2, indeed, suggests that these compounds are anti-inflammatory, but have an ulcer sparing effect. Clinical data with meloxicam also suggest that this theoretical effect is also translated into patient benefit. The selective inhibition of COX 2 is a very attractive new concept that has revitalised NSAID research and promises future hope for the treatment of inflammatory disease without gastric side effects.

Two isoforms of cyclooxygenase (COX) are described: COX-1 is a constitutive enzyme and is widely expressed in most tissues, COX-2 is an inducible enzyme and is abundant throughout the gastrointestinal tract. Expression of COX-2 can be induced locally by inflammatory stimuli and appears coincident with local prostaglandin (PG) production. Currently available non-steroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases; however, significant side-effects due to inhibition of COX-1 limit their use. Inhibitors of COX-2 are as active as non-selective NSAIDs and inhibit PG synthesis in inflammatory cells. In contrast to other NSAIDs, selective COX-2 inhibitors do not cause ulcers in the stomach or intestine.

The high genetic variability of the 5' end of the envelope protein-coding region E2 (HVR1 E2) of Hepatitis C Virus (HCV) RNA has been suggested by many authors to play an important role in both virus persistence and outcome of liver disease. We studied the relations between HVR1 E2 variability and HCV genotypes, HCV-RNA levels and liver disease in 8 chronic HCV carriers (5 males and 3 females, median age 41 years, followed-up for a mean period of 3 years). Four were healthy HCV carriers with persistently normal ALT levels and normal liver histology and 4 patients with chronic liver disease. In each patient, the HVR1 E2 variability of 2 serum HCV-RNA isolates obtained at least 12 months apart were evaluated by direct sequencing. Nucleotide and amino acid homologies ranged between 97.6%-57.1% and 92.8%-25% in healthy carriers and 95.2%-55.9% and 89.3%-32.1% in patients, respectively. We did not observe any correlation between HVR1 E2 heterogeneity and HCV genotypes, viraemia levels, presence and extent of liver necroinflammation. Our findings suggest that HVR1 E2 heterogeneity has no direct implications in hepatitis, pathogenesis but it could play a major role in virus persistence.

This study was undertaken to evaluate the influence of age on the content of glutathione, and its amino-acid precursor cysteine and on the activity of glutathione-S-transferase of gastric mucosa in man. We examined 44 gastric mucosal samples taken from the body and the antrum of the stomach of 22 healthy subjects, aged between 19 and 65 years. The results were examined in relationship to their distribution in the stomach, to the sex and to the age of the subjects. Glutathione and glutathione-S-transferase were higher in the gastric body than in the antrum, without differences between males and females. The activity of glutathione-S-transferase was directly related to glutathione content and both decreased with age. Cysteine was not influenced by any of the factors considered. These data indicate that the antioxidative and detoxifying capability of gastric mucosa decreases with age in man.

The case of an infant with Sandifer syndrome is reported. Real-time ultrasonography showed delayed gastric emptying time, which returned to normal when the patient was asymptomatic. The importance of gastric motility investigations in Sandifer syndrome is stressed since delayed gastric emptying could play a role in the pathogenesis of this disease.

NSAIDs are among the most frequently prescribed drugs worldwide. Unfortunately acute and especially chronic NSAID intake is accompanied by untoward side effects of the digestive system, particularly the gastroduodenal tract. Erosions and ulcers are more common in the stomach, but also the duodenal mucosa can be involved. Elderly patients are the subjects most at risk of developing gastric lesions, which are often asymptomatic. Complications such as bleeding and perforation may suddenly occur, sometimes with a fatal outcome. Epidemiological data and risk factors are reviewed and commented in detail.

In the spring of 1994, the occurrence of Hepatitis E virus antibodies was evaluated in 653 subjects representing all age-groups in the general population of a Central Italian town, where a high hepatitis C virus prevalence had been reported. The overall anti-HEV prevalence was 2.6% ranging from 1.4% in the 30-49 age-group to 5.7% (p < 0.01) in the 60-70 age-group; none of the subjects under 30 years of age were positive. Sociodemographic variables, such as family size and years of schooling were not associated with HEV exposure. Anti-HEV positivity was found in 1.8% (1/56) of the subjects who were positive for anti-HCV and in 2.7% (16/597) of those who were anti-HCV negative (O.R 1.5; C.I.: 95% = 0.2-11.7). Thus no association was found between HEV and HCV infections. These data suggest a past spread of HEV in this area and underline the occurrence of long-lasting antibodies in infected subjects.

Case of an infant with chronic cough is reported. The most frequent causes of chronic cough were ruled out. Twenty-four hour oesophageal pH-monitoring showed a close correlation between gastro-oesophageal reflux episodes and cough attacks. The patient was successfully treated with cisapride (0.3 mg/kg t.i.d.). These findings show that irritable oesophagus syndrome can cause chronic cough.

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.