Synthesis and glycogen phosphorylase inhibitor activity of functionalized 1,4-benzodioxanes.

A series of novel 1,4-benzodioxanes 11a-e and rac-12a-d carrying thiazolidine-2,4-dione moiety was synthesized and their glycogen phosphorylase inhibitor activity was also evaluated.

Peroxynitrite decreases arrhythmias induced by ischaemia reperfusion in anaesthetized dogs, without involving mitochondrial KATP channels.

BACKGROUND AND PURPOSE: Exogenous peroxynitrite from nanomolar to micromolar concentrations exerts cardioprotection. Here, we have assessed its effects on ischaemia- and reperfusion-induced ventricular arrhythmias in vivo and a possible role for mitochondrial K(ATP) channels in these effects, using the channel inhibitor 5-hydroxydecanoate (5-HD). EXPERIMENTAL APPROACH: Chloralose-urethane-anaesthetized dogs were treated twice for 5 min with peroxynitrite (100 nM, by intracoronary infusions) in both the absence and presence of 5-HD (150 microg kg(-1) min(-1)), and then subjected to 25 min occlusion of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, as well as the levels of nitrotyrosine were assessed and compared with a group of control dogs, subjected only to a 25 min occlusion and reperfusion insult. KEY RESULTS: Compared with controls, infusion of peroxynitrite markedly suppressed the number of ventricular premature beats (388+/-88 vs 133+/-44), the incidence of ventricular fibrillation both during occlusion (50% vs 10%) and reperfusion (100% vs 44%), and increased survival (0% vs 50%; all P<0.05). The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) during occlusion and nitrotyrosine levels on reperfusion were significantly less in the peroxynitrite-treated dogs than in the controls. 5-HD did not modify the cardioprotective effects of peroxynitrite. CONCLUSION AND IMPLICATIONS: Exogenous peroxynitrite provided antiarrhythmic protection in vivo, which might have been on account of a reduction in endogenous peroxynitrite formation. This protection seemed not to be mediated through mitoK(ATP) channels.

Chiroptical properties of 2,3-dihydrobenzo[b]furan and chromane chromophores in naturally occurring O-heterocycles.

The correlation between the helicity (absolute conformation) of the O-heterocyclic ring of chiral 2,3-dihydrobenzo[b]furan (1) and chromane (2) derivatives and their (1)L(b) band CD was investigated. The same helicity rule was found for both unsubstituted chromophores: P/M helicity of the heterocyclic ring leads to a negative/positive CD within the (1)L(b) band. While the substitution of the fused benzene ring by achiral substituents does not change this helicity rule for the chromane chromophore, it leads to its inversion for the 2,3-dihydrobenzo[b]furan chromophores. On the basis of these observations, the published absolute configurations of natural flavonol and pterocarpan derivatives were confirmed and the configurational assignments of several natural neolignans revised.

Simple synthesis of benzofuranoid neolignans from Myristica fragrans.

The total synthesis of four neolignans-fragnasols A (1), B (2), and C (3) and dehydrodiisoeugenol (4)-starting from the readily available phenol derivative isoeugenol (5) was accomplished. The key step of the synthesis of these natural products is a novel type of dimerization of 5 into 4 with iodobenzene diacetate.

Octreotide in the prevention of pancreatic injury associated with endoscopic cholangiopancreatography.

BACKGROUND: Data on whether long-acting somatostatin analogue octreotide causes or prevents pancreatic injury following endoscopic retrograde cholangiopancreatography (ERCP) are controversial. AIM: This multicentre, prospective trial studied the effect of octreotide on pancreatic injury in a large unselected group of patients after ERCP and endoscopic sphincterotomy. METHODS: The study was carried out in a prospective random manner on 2102 patients in 11 endoscopic centres. Patients in the study received 0.1 mg octreotide acetate and those in the control group received isotonic sodium chloride, subcutaneously before and 45 min after ERCP. Pancreatic injury was assessed by clinical symptoms such as pain, fever and abdominal tenderness. Serum amylase and blood sugar were determined prior to, and 6 and 24 h after the endoscopic procedure. RESULTS: Data from 599 patients in the study group and 600 in the control group were included in the final evaluation. When all the patients were considered, octreotide did not induce pancreatic injury as assessed by clinical symptoms, and diminished the increase of serum amylase levels following ERCP. However, when subgroups of patients were studied, the frequency of increased amylase levels decreased significantly in patients with chronic obstructive pancreatitis and in patients who underwent endoscopic sphincterotomy (P < 0.01). The peak serum glucose level was higher in the treated group when compared to the controls. CONCLUSION: The prophylactic use of long-acting somatostatin does not alter the frequency of post-ERCP pancreatic injury, but it may diminish the rate of increased serum amylase levels in patients with chronic obstructive pancreatitis and also in those with an endoscopic sphincterotomy.

A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.

BACKGROUND: Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. METHODS: We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months. RESULTS: At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P=0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated. CONCLUSIONS: In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.

Ebrotidine versus ranitidine in the healing and prevention of relapse of duodenal ulcer. A multicentre, double-blind, parallel, randomized, controlled study.

Two hundred and fifty patients were included in a double-blind, parallel, randomized, controlled clinical trial. Duodenal ulcer treatment lasted up to 8 weeks. Forty-nine patients were followed up for prevention of ulcer relapse for up to one year. All patients received either ranitidine (300 mg/day in the healing phase and 150 mg/day in the follow-up phase) or ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4 -thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide , CAS 100981-43-9, FI-3542) (400 mg/day in both phases) as a single dose at bedtime. Both groups were matched in all demographic parameters, except for a significantly higher percentage of smokers in the ranitidine group. The percentage of total healing was almost the same with both products. Healing occurred in a higher percentage with ebrotidine at weeks 4 (75% versus 66.7%) and 6 (87% versus 79.7%). A higher effect of ebrotidine on the incidence of duodenitis was identified during the whole study, but only reached statistical significance at week 6. The relapse rate during the follow-up phase showed no differences between the two study treatments, relapse percentage figures being 25% for ebrotidine and 24% for ranitidine. There were no differences in the number of unscheduled visits between the two groups, although 57% of patients in the ranitidine group had to make a second follow-up visit, as compared with 33% in the ebrotidine group. Both drugs caused hardly any side effects, affecting only one patient from each group: one patient with ebrotidine suffered from diarrhoea and one patient with ranitidine developed a skin rash on the limbs. Administration of ebrotidine in a single dose (400 mg/d) was at least as effective and safe as ranitidine both for healing and relapse prevention in patients with duodenal ulcer.

[Evaluation of the effectiveness of pantoprazole and ranitidine in the treatment of duodenal ulcer. Result of an international multicenter study]. / A pantoprazol és a ranitidin hatékonyságának vizsgálata nyombélfekély kezelésére. Nemzetközi multicentrikus vizsgálat eredménye.

A double-blind, randomized, multicenter, multicountry study (Poland, Chech Republic, Hungary) was carried out in 1995 on patients (n = 326) with endoscopically confirmed duodenal ulcer treated with ranitidine vs. pantoprazole. In Hungary-in 4 gastroenterology centers-123 patients have been involved (age 18-75 years). The treatment schedule has been 300 mgs of ranitidine or 40 mgs of pantoprazole q. d. for 2 or if necessary for 4 weeks. In the Hungarian study 60 DU patients were treated with pantoprazole vs. 63 ones with ranitidine. Having finished the two-week schedule the healing rates of duodenal ulcer were as follows: pantoprazole 71%/72% (Hungary/International) vs ranitidine 57%/51%, (p < 0.001). After 4 weeks the corresponding values showed the following: pantoprazole 98%/94% vs. ranitidine 88%/86%, respectively, (p < 0.005). Both drugs have shown to be effective and safe to cure duodenal ulcer however in our study pantoprazole was significantly more efficacious and provided quicker healing than ranitidine.

[Complex screening of family members at risk for familial adenomatous polyposis]. / Familiáris adenomatosus polyposisos családok praesymptomás diagnosztikán alapuló komplex gondozása.

151 members of 10 affected families with FAP have been registered at the authors' regional polyposis registry, among them 51 FAP patients were verified histologically. The disorder is autosomal dominant thus the chance for the inheritance of the mutated allele is fifty percent in the offspring of an affected patient. Because of the high risk the registration and regular control of family members is recommended. They can be divided into high risk and low risk group based on presymptomatic tests. The examination of retina pigmentepithel was the only possibility for presymptomatic diagnosis earlier. After localization and identification of APC gene responsible for the disease molecular genetic methods have been introduced for presymptomatic diagnosis. The authors performed presymptomatic tests based on ophthalmologic and molecular genetic methods among family members at risk. Ophthalmologic examination was done in 53 while molecular genetic investigation in 54 cases. All the results of endoscopic, ophthalmological and molecular genetic examinations were available in 35 persons, among them 19 FAP have been found. Ophthalmological examination were informative in 33 out 35 cases (unequivocal positive or negative) while results of molecular genetic methods and sigmoidoscopy were correlated in every case. Authors stress the significance of complex screening of affected families with FAP in the prevention of colorectal cancer and extracolonic malignant processes.

[Octreotide in the prevention of hyperamylasemia following ERCP (a controlled multicenter study)]. / Octreotid az endoszkópos retrográd cholangiopancreatographiát követó hyperamylasaemia prevenciójában (Multicentrikus kontrollált tanulmány).

UNLABELLED: The aim of the multicentric trial was to study the effect of octreotide (Sandostatin) on the rise of pancreatic amylase in the serum after ERCP based on a large number of patients. The study was carried out in a prospective random manner in 2102 patients in 11 endoscopic centers. Patients in the treated group received 0.1 mg octreotide acetate, and those of the nontreated (control) group received isotonic sodium-chloride subcutaneously before the ERCP and 45 minutes after. Serum amylase and blood sugar were checked before the endoscopic procedure, 6 and 24 hours later. Out of the total number of patients involved, data of 1199 patients (599 in the treated group, and 600 in the control group) were evaluated. Octreotide diminished the percentual increase of serum amylase levels following ERCP. However, the frequency of hyperamylasaemia was decreased only after in patients with chronic obstructive pancreatitis or in such patients after endoscopic sphincterotomy. The peak serum level of blood sugar was higher in the treated group compared to the controls. There was no difference in the clinical symptoms following ERCP between the two groups. CONCLUSION: the prophylactic use of long-acting somatostatin may diminish the frequency of hyperamylasemia after ERCP in patients with chronic obstructive pancreatitis or in those patients who subsequently underwent EST.