Graves眼病合并真菌性角膜感染1例

报道1例应用大剂量糖皮质激素治疗Graves眼病后导致的真菌性角膜感染。一位31岁的甲状腺机能亢进同时伴有双眼突出的女性,视力下降、眼睑浮肿。首先应用抗甲状腺药物(甲巯咪唑),1个月后,突眼症状无改善,遂给予大剂量甲强龙冲击和曲安奈德球后注射以减轻症状。3个月后,该患者出现角膜溃疡,双眼无光感。1周后体温升高,最高达39.5℃,给予抗菌治疗后体温仍波动在36.7～37.3℃之间。角膜溃疡分泌物涂片可见真菌芽孢和菌丝,予甲亢、抗真菌和营养支持治疗。1个月后,患者双眼睑浮肿减轻、角膜溃疡面积减少,视力恢复到可有光感,体温降至正常。     

硫酸糖肽的生物活性及药理作用

黏多糖类物质独特的生物活性已成为生物化学和医学领域的热点。硫糖肽作为黏多糖类的一种,具有广泛的抗炎、抗溃疡作用,尤其是预防和治疗溃疡方面的优势引起人们越来越多的关注,具有广阔的药物开发和应用前景。本文就硫糖肽的生物活性及其药理作用展开综述,并结合硫糖肽的市场需求和研究现状进行了展望。     

Short peptide fragments with antiulcer activity from a collagen hydrolysate

A peptide acidic hydrolysate of collagen (PHC) was obtained under conditions (4 N HCl) ensuring the predominant formation of short peptides, glyprolines. They were separated and their antiulcer activity was studied. Thirty individual peptides with molecular masses of 174–420 amu were isolated from the PHC by HPLC. The PHC was shown to predominantly contain 2-to 4-aa peptides, including PG, GP, and PGP. Experiments on rats demonstrated that, on intragastric administration at a dose of 1 mg/kg, PHC enhances the stability of the gastric mucosa to the action of ulcerogenic factors, such as ethanol and stress, and exhibits a protecting antiulcer effect. Even a lesser dose (0.1 mg/kg), which reduced ulcer area twofold, was effective in the stress model of ulcer formation. The intraperitoneal and intragastric administration of PHC at a dose of 1 mg/kg was found to exhibit a therapeutic effect in the acetate model of ulcer formation.     

Efficacy and safety of rabeprazole, amoxicillin, and gatifloxacin after treatment failure of initial Helicobacter pylori eradication

OBJECTIVES: To evaluate the efficacy of a 7-day regimen of gatifloxacin (400 mg daily), amoxicillin (1 g twice a day), and rabeprazole (20 mg twice a day) in the secondary eradication of Helicobacter pylori infection. METHODS: Eligible patients with persistent infection following one or more conventional clarithromycin-containing triple therapies were enrolled in this open-label trial. Eradication of infection was documented by (14)C-urea breath test a minimum of 4 weeks after therapy and 2 weeks off any acid suppressive therapy. Culture of H. pylori and in vitro susceptibility testing to amoxicillin, clarithromycin, and gatifloxacin was done in cases of failed eradication. RESULTS: A total of 45 patients (22 females:23 males; mean age 44.5 +/- 13 years) were enrolled. Eradication occurred in 38 patients [both per-protocol (PP) and intention-to-treat analysis: 84.4%; 95% CI: 74-95%]. No significant adverse effects were reported. In vitro susceptibility testing showed no secondary resistance to gatifloxacin or amoxicillin in any of the seven nonresponders. Smoking, age, and sex were not predictors of potential eradication failure. CONCLUSIONS: A 7-day regimen of gatifloxacin, rabeprazole, and amoxicillin is effective after failed eradication therapy for H. pylori and does not appear to result in secondary resistance. This combination is simple, well tolerated, and may lead to higher compliance and lower costs.     

Interaction of Helicobacter pylori Infection and Nonsteroidal Anti‐Inflammatory Drugs in Gastric and Duodenal Ulcers

Background: Gastric (GU) and duodenal ulcers (DU) are in most instances either induced by Helicobacter pylori infection or by nonsteroidal anti‐inflammatory drugs (NSAIDs). Whether eradication of H. pylori is beneficial in NSAID users for preventing NSAID induced GU and DU has been the focus of different studies. Materials and Methods: Mechanisms shared by both H. pylori and NSAIDs for the induction of GU and DU were reviewed and randomized controlled trials on H. pylori eradication for prevention and healing of GU and DU in patients requiring NSAID therapy were identified by a PubMed search. Results: Key factors in the induction of GU and DU for both H. pylori and NSAIDs are a decrease in pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonucleates in distinct compartments. For primary ulcer prevention, H. pylori eradication before starting an NSAID therapy reduces the risk of NSAID induced GU and virtually abolishes the risk of DU. H. pylori eradication alone is not sufficient for secondary prevention of NSAID induced GU and DU. H. pylori infection appears to further increase the protective effects of proton‐pump inhibitors (PPI) to reduce the risk of ulcer relapse. H. pylori eradication does not influence the healing of both GU and DU if NSAID intake is discontinued. Conclusions: Duodenal ulcer is more closely related to H. pylori infection than GU in NSAID users. H. pylori eradication is recommended for primary prevention of GU and DU in patients requiring NSAID therapy. PPI therapy is mandatory for secondary prevention of gastroduodenal ulcers, and appears to further reduce the risk of ulcer relapse in the presence of H. pylori.     

Molecular fingerprinting of Helicobacter pylori strains from duodenal ulcer patients

AIMS: To characterize the molecular fingerprinting of Helicobacter pylori population isolated in duodenal ulcer patients treated with triple therapy. METHODS AND RESULTS: Gastric biopsy specimens from corpus and antrum, were cultured for H. pylori isolation. Helicobacter pylori eradication was evaluated after 4 and 16 weeks. DNAs of all isolates were characterized by random amplified polymorphic DNA typing and cagA gene was also detected. After the therapy, five patients harboured the microorganism at 4 weeks and two of them remained H. pylori positive at 16 weeks. The analysis of DNA fingerprinting of strains isolated from antrum and corpus of patients susceptible to treatment, showed similar patterns. Instead, when the therapy was not effective, strains isolated from sequential biopsies from initial and after 4 and 16 weeks, showed distinct fingerprintings and retained the cagA status, over time. CONCLUSIONS: The drugs used for therapy could exercise an effect in genotypical rearrangement among H. pylori cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The variableness among H. pylori strains represents a way to challenge environmental stress.     

The diversity of vacA and cagA genes of Helicobacter pylori in East Asia

It has been reported that Helicobacter pylori infection with the type I strain, which expresses the VacA and CagA antigens, is associated with duodenal ulcer. We examined the diversity of vacA and cagA genes in 143 isolates obtained from patients with duodenal ulcer or chronic gastritis in East Asia (two different areas of Japan, Fukui and Okinawa, and also in Hangzhou, China) by polymerase chain reaction (PCR) and sequence analysis. Diversities of cagA and vacA genes were detected in East Asia. The prevalence of cagA-positive H. pylori was significantly different between Fukui and Okinawa (P=0.0032). The prevalence of Western type CagA was significantly higher in Okinawa than in Fukui (P<0.0001). However, there was no significant association between the genotype of cagA and clinical outcome. In Japan, the predominant vacA genotype was s1c/m1b. In contrast, in Hangzhou, the predominant vacA genotype was s1c/m2, and they were all East Asian CagA-positive. These findings suggest that a distinct distribution of the vacA and cagA genotypes is present in East Asia, regardless of clinical outcome.     

Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer

We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers.     

Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users

Background. The recently reported OMNIUM and ASTRONAUT NSAID ulcer prevention trials using omeprazole to prevent endoscopic ulcer recurrence among chronic NSAID users suggested superiority over misoprostol or ranitidine. Aim. To test the hypothesis the results from the OMNIUM and ASTRONAUT studies would not be generalizible as ulcer healing and ulcer recurrence would differ in relation to Helicobacter pylori status. Methods. The data regarding H. pylori status were made available by AstraZenca allowing separate analysis of the outcome of those with NASID ulcers (i.e. without H. pylori infection) and those NSAID use was complicated with the presence of an active H. pylori infection. Results. Reanalysis confirmed that omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, overall omeprazole was not significantly better than the subtherapeutic dose (400 µg/day) of misoprostol (14.5% vs. 19.6%, respectively, p = .93); 400 µg of misoprostol was actually superior to omeprazole for the prevention of gastric ulcers among those NSAID ulcers (8.2% vs. 16.6% for misoprostol and omeprazole, respectively; p < .05). Omeprazole was also not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Omeprazole was not significantly different from 300 mg of ranitidine for the prevention of NSAID gastric ulcers (14.6% vs. 11.6%, respectively, p = .56). Duodenal ulcers were over represented among H. pylori infected NSAID users and duodenal ulcer prevention was more sensitive to acid suppression than gastric ulcer. Conclusion. The OMNIUM and ASTRONAUT trials may have provided an unrealistic sense of security regarding the effectiveness of omeprazole for protection against ulcer recurrence in chronic NSAID users.