Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen

BACKGROUND: Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients. METHODS: We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months. RESULTS: We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005). CONCLUSIONS: Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.     

Endogenous RGS proteins enhance acute desensitization of GABAB receptor-activated GIRK currents in HEK-293T cells

The coupling of GABA_B receptors to G-protein-gated inwardly rectifying potassium (GIRK) channels constitutes an important inhibitory pathway in the brain. Here, we examined the mechanism underlying desensitization of agonist-evoked currents carried by homomeric GIRK2 channels expressed in HEK-293T cells. The canonical GABA_B receptor agonist baclofen produced GIRK2 currents that decayed by 57.3±1.4% after 60 s of stimulation, and then deactivated rapidly (time constant of 3.90±0.21 s) upon removal of agonist. Surface labeling studies revealed that GABA_B receptors, in contrast to µ opioid receptors (MOR), did not internalize with a sustained stimulation for 10 min, excluding receptor redistribution as the primary mechanism for desensitization. Furthermore, heterologous desensitization was observed between GABA_B receptors and MOR, implicating downstream proteins, such G-proteins or the GIRK channel. To investigate the G-protein turnover cycle, the non-hydrolyzable GTP analogue (GTPS) was included in the intracellular solution and found to attenuate desensitization to 38.3±2.0%. The extent of desensitization was also reduced (45.3±1.3%) by coexpressing a mutant form of the Gq G-protein subunit that has been designed to sequester endogenous RGS proteins. Finally, reconstitution of GABA_B receptors with Go G-proteins rendered insensitive to RGS resulted in significantly less desensitization (28.5±3.2%). Taken together, our results demonstrate that endogenous levels of RGS proteins effectively enhance GABA_B receptor-dependent desensitization of GIRK currents.     

子宫颈病变及子宫颈癌的细胞病理诊断

对５１例巴氏分级属非癌及４９例巴氏分级属癌或高度可疑癌患者的子宫颈和子宫腔刮片进行细胞病理诊断，结果表明，用细胞病理学方法观察和分析刮片细胞，可以将巴氏分级诊断所不能区分的宫颈腺性糜烂，化生、上皮内瘤变及不同组织类型的子宫颈瘤予以分清，达到疾病诊断的目的，对癌变可以进行组织类型及分化程度的判断。提示：细胞病理诊断方法估巴氏分级诊断方法。     

Suppressive effects of ketotifen on Th1- and Th2-related chemokines of monocytes

Ketotifen is a mast cell stabilizer and useful in younger children with allergic diseases such as asthma and allergic rhinitis. Macrophage-derived chemokine (MDC) is a T-helper cell type 2 (Th2)-related chemokine involved in recruitment of Th2 cells toward allergen-challenged inflammation. However, the Th1-related chemokines, interferon-inducible protein 10 (IP-10)/CXCL10, and the monokine induced by interferon-gamma (MIG)/CXCL9 are also important in allergen-induced asthma in animal models. We investigated the effects of ketotifen on the expression of Th1- and Th2-related chemokines of human monocytes in vitro and ex vivo. Ketotifen (5-50 microM) significantly down-regulated lipopolysaccharide (LPS)-induced MDC, MIG and IP-10 (p < 0.05, each comparison) in THP-1 cells and human primary monocytes in a dose-dependent manner. SB203580 [p38-mitogen-activated protein kinase (MAPK) inhibitor] suppressed LPS-induced MDC and IP-10 expression, and PD98059 (ERK-MAPK inhibitor) could only suppress LPS-induced IP-10, but not MDC expression. LPS-induced pp38 and p-ERK expression of THP-1 monocytic cells was suppressed by ketotifen. These data demonstrate that ketotifen is effective in down-regulating LPS-induced MDC, MIG and IP-10, which play important roles in the pathogenesis of airway inflammation. The suppressive effect on MDC and IP-10 may, at least in part, involve the down-regulation of LPS-induced p38 and ERK-MAPK expression.     

Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training

Few studies are available about the evaluation of resistance training in patients with protein-energy malnutrition. To assess the effects of resistance training on the recovery of nutritional status of patients with short bowel syndrome, with a small bowel remnant of less than 100 cm, 9 patients of both sexes with protein-energy malnutrition after extensive resection of the small bowel were submitted to resistance training of progressive intensity consisting of concentric and eccentric work exercises for the upper limbs, trunk, and lower limbs, with the individuality and limitations of each patients being respected. Food consumption was monitored by 24-hour food recall performed during the initial phase of the study, before and 7 and 14 weeks after physical training, and by a dietary record for a period of 3 days of oral feeding. The nutrients administered by the enteral and parenteral route were recorded. A significant increase in total arm area (P ≤ .01) and fat-free mass (P ≤ .01) was observed as determined by computed tomography. An increase in total energy ingestion and carbohydrate consumption (P ≤ .01) was also observed. In addition, the activity of the enzyme carnosinase was increased after resistance training (P ≤ .01). The present results show that resistance training in patients with short bowel syndrome and protein-energy malnutrition can be considered to be a part of the nonmedicamentous treatment of these patients, leading to better nutrient use and to a gain of lean mass.     

The Effect of Cytokines on the Activation-Induced Apoptosis of B Cells in Autoimmune NZB X NZW F1 Mice

Programmed cell death (apoptosis) is an essential process in the development of various tissues and its involvement has been proposed for the elimination of self-reactive immature T and B lymphocytes when self antigens are first encountered. In order to further investigate the role of apoptosis in the pathogenesis of autoimmune disease, the apoptosis of lipopolysaccharide (LPS)-activated B cells, peritoneal cells from NZB x NZW F1 (NZB/W F1) mice and nonautoimmune BALB/c mice were assayed using an in vitro culture system. Splenic B cells were isolated and then stimulated with LPS before further activated with crosslinking antimu antibody. In addition, the apoptosis of peritoneal cells induced by crosslinking antimu antibody was also analyzed. The data revealed that the specific apoptosis of both activated B cells and peritoneal cells induced by crosslinking antimu antibody was very similar comparing NZB/W F1 and nonautoimmune BALB/c mice. This activation-induced B-cells apoptosis could be rescued, however, with the addition of cytokines such as interleukin (IL)-5 or IL-10, to the culture. The results suggest that there is no endogenous defect in the apoptosis of activated B cells for autoimmune NZB/W F1 comparing nonautoimmune BALB/c mice. Notably, however, abnormally high levels of the type 2 T helper (Th2)-related cytokines such as IL-5 or IL-10 may play an important role in the abnormal expansion of activated B cells in autoimmune NZB/W F1 mice.