Gastrointestinal tolerability of metamizol,acetaminophen, and diclofenac in subchronic treatment in rats

The gastrointestinal tolerability of metamizol and acetaminophen [weak cyclooxygenase (COX) inhibitors] in comparison with diclofenac (nonselective cyclooxygenase inhibitor) was evaluated in subchronic treatments in rats. Wistar rats recived 60 mg/kg body weight of metamizol and acetaminophen, and 3 mg/kg body weight of diclofenac by oral route twice daily for 14 days. Myeloperoxidase activity, an index of neutrophil infiltration, COX expression and the effects on blood parameters used as indicators of liver and renal functions were also studied. Metamizol and acetaminophen did not cause apparent gastrointestinal lesions; in contrast diclofenac showed swelling and an increased thickness on the distal intestinal mucosa. Myeloperoxidase activity was significantly increased in the small bowel with diclofenac treatment. In gastric mucosa the expression of the cyclooxygenase-1 was not affected and the expression of cyclooxygenase-2 was not observed. Diclofenac treatment significantly diminished hematocrit, hemoglobin, and corpuscular volume and increased the number of platelets. Aspartate aminotransferase and -glutamyltransferase activity were also altered and, regarding the renal biochemical parameters, the animals treated with diclofenac had increased urea values. In contrast, acetaminophen treatment did not affect either of these parameters and metamizol increased only the alanine aminotransferase activity. Under our experimental conditions, metamizol and acetaminophen seem to be safe drugs. In contrast, with diclofenac treatment blood loss and anemia are observed which could stem from the small intestinal injury. Moreover, this drug could to impair kidney function.     

ADP受体阻滞剂的研究进展

ADP受体阻滞剂是一类与血小板的ADP受体特异性结合从而抑制血栓形成的一类药物。该类药物选择性的作用于血小板的ADP受体(P2Y1和P2Y12受体),抑制血小板膜ADP受体的表达、结合及其活性,从而有效的抑制了血小板的聚集和血栓的形成。目前应用于临床药物有噻氯匹定、氯吡格雷。还有多个药物正处于临床试验或临床前期实验中。现对ADP受体阻滞剂在抗血小板形成药物中的重要地位、研究进展和开发前景进行综述,为该类药物的研发提供依据。     

大鼠乙酸性胃溃疡复发模型的复制及健胃愈疡颗粒的干预作用

[目的]复制大鼠乙酸性胃溃疡复发模型并观察健胃愈疡颗粒（JWYY）的干预作用。[方法]采用改良Okabe乙酸涂抹法制作大鼠胃溃疡模型，腹腔注射白细胞介素1β（IL-1β）致愈合溃疡复发。44只大鼠随机分为正常对照组、假手术组、模型复发组、模型未复发组、JWYY组、奥美拉唑（OMLZ）组，观察各组胃溃疡复发率、胃蜜大体改变、胃窦组织病理学改变、炎症细胞密度计数。[结果]模型复发组胃溃疡复发率为87．50％，呈溃疡病理结构改变，溃疡边缘见残留之再生黏膜，再生黏膜较薄，有较多炎症细胞浸润。JwYY能改善胃溃疡愈合，减低IL-1β所诱导的瘢痕黏膜炎症细胞浸润的密度，降低溃疡复发率，与OMLZ无显著差别。[结论]IL-1β可能通过炎症细胞浸润诱导愈合的乙酸性胃溃疡复发；抑制炎症反应可能是JWYY抗溃疡复发的疗效机制之一。     

Inhibitory effects of aspirin and indometacin on the growth of Helicobacter pylori in vitro

OBJECTIVE: The interactions between non‐steroidal anti‐inflammatory drugs and Helicobacter pylori have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of aspirin and indometacin on the growth of H. pylori and to determine the effects of aspirin on the susceptibility of H. pylori to some antimicrobials. METHODS: Kinetic studies were performed by inoculating strains of H. pylori in brucella broth with different concentrations of aspirin and indometacin. Growth of bacteria in the broth was assessed spectrophotometrically and by viable colony counts after incubation for 24 and 48 h. Bacterial morphology was determined by Gram stain under light microscopy. The minimal inhibitory concentration (MIC) of aspirin and indometacin was determined by the standard agar dilution method. The MIC of amoxicillin, clarithromycin and metronidazole was measured in the presence and absence of aspirin by the E‐test method. RESULTS: Kinetic studies revealed that aspirin and indometacin inhibited the growth of H. pylori in a dose‐dependent manner. The bactericidal activity of these agents was expressed by cell lysis. Aspirin at 400 µg/mL produced an almost 2‐log decrease in the number of CFU/mL at 48 h. Similar inhibitory effects were obtained when 100 µg/mL indometacin was tested. The MIC at which 90% of H. pylori was inhibited was 512 µg/mL and 128 µg/mL for aspirin and indometacin, respectively. Increased susceptibility of H. pylori to amoxicillin, clarithromycin and metro­nidazole was found in the presence of aspirin. CONCLUSIONS: Aspirin and indometacin could significantly inhibit the growth of H. pylori when incubated in brucella broth in vitro. A subinhibitory concentration of aspirin enhanced the susceptibility of H. pylori to some antimicrobial agents.     

Spironolactone improves lung diffusion in chronic heart failure.

AIMS: To evaluate whether anti-aldosteronic treatment influences lung diffusion (DLCO) in chronic heart failure (HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLCO abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. METHODS AND RESULTS: Thirty stable chronic HF patients, with reduced DLCO (<80% of predicted), were randomly assigned to active treatment (25 mg spironolactone daily) or placebo in addition to conventional anti-failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLCO and membrane diffusing capacity (DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLCO due to an increase of DM (DLCO: 18.3+/-3.9 vs. 19.9+/-5.5 mL/min/mmHg; DM: 28.1+/-7.7 vs. 33.3+/-8.6 mL/min/mmHg) and peak oxygen consumption (peak VO2 16.8+/-1.9 vs.18.6+/-2.2 mL/min/kg). Increments of DLCO and peak VO2 were linearly related (R=0.849, P<0.001). CONCLUSION: These data show a positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti-aldosteronic drugs improve HF clinical condition and prognosis.     

Influence of Oral Antidiabetic Drugs on Hyperglycemic Response to Foods in Persons with Type 2 Diabetes Mellitus as Assessed by Continuous Glucose Monitoring System: A Pilot Study

Background

The purpose of this prospective open-label trial was (1) to assess the influence of oral antidiabetic drugs (OAD) on the glycemic index (GI), glucose response curves (GRCs), daily mean plasma glucose (MPG) and (2) to compare the GI of foods in persons with OAD-treated type 2 diabetes mellitus (T2DM) with the respective GI in healthy persons (HP).

Methods

Tested foods containing 50 g of carbohydrates were eaten for breakfast and dinner after 10 and 4 h of fasting, respectively. Glycemic index, GRC, and MPG were obtained using the CGMS^®System Gold™ (CGMS). In T2DM patients [n = 16; age (mean ± standard error) 56.0 ± 2.25 years], foods were tested four times: tests 1, 2, and 3 were performed within one week in which placebo was introduced on day 2, and test 4 was carried out five weeks after reintroduction of OAD. Glycemic indexes, GRC, and MPG from tests 1, 2, 3, and 4 were compared. In a control group of 20 HP (age 24.4 ± 0.71 years), the mean GIs were calculated as the mean from 20 subject-related GIs.

Results

In T2DM patients, subject-related assessment of GIs, GRC, and MPG distinguished persons with and without OAD effect. Nevertheless, the group-related GIs and the MPG on days 2, 8, and 39 showed no significant difference. There was no significant difference between the GIs in OAD-treated T2DM patients (test 4) versus HP (except in apple baby food). Glucose response curves were significantly larger in T2DM patients (test 4) versus HP.

Conclusions

Determination of GRC and subject-related GI using the CGMS appears to be a potential means for the evaluation of efficacy of OAD treatment. Further studies are underway.     

Serial electrophysiologic studies after single chamber atrial pacemaker implantation in patients with symptomatic sinus node dysfunction

After single chamber atrial pacemaker implantation, serial electrophysiologicstudies were performed noninvasively at intervals of 3 monthsover a total period of 3 years in 24 patients with symptomaticsinus node dysfunction. All patients underwent invasive electrophysiologicstudies before pacemaker implantation and demonstrated intactanterograde AV conduction. Patients were divided into 2 groupsgroup I did not require antiarrhythmic drugs during follow-upwhereas group 2 received antiarrhythmic drugs. In group 1(11 patients) the atrial paced heart rate producingAV Wenckebach phenomenon (AVWHR) remained stable during a meanfollow-up of 22±10 months, with a variability not exceeding10 beats min^–1 with respect to the initial AVWHR obtainedduring preoperative electrophysiologic study. In group 2 (13patients) with a mean follow-up of 15±8 months a meandecrease of AVWHR of 19.2±17.5 beats min^–1 waspresent between AVWHR before and 3 months after initiation oforal antiarrhythmic drugs (P<0.01) During chronic (>3months) antiarrhythmic drug therapy the variability of the AVWHRnever exceeded 10 beats min^–1 with respect to the AVWHRobtained 3 months after the initiation of oral drug therapy. Deterioration of anterograde AV conduction during long-termfollow-up of patients with symptomatic sinus node dysfunctionand intact anterograde AV conduction at the time of pacemakerimplantation is a consequence of orally taken antiarrhythmicdrugs, rather than a consequence of degeneration of the AV conductingsystem.     

Elevated risk of death and major cardiovascular events in subjects with newly diagnosed diabetes: Findings from an administrative database

AimsTo investigate the incidence of major cardiovascular complications and mortality in the first years of follow-up in patients with newly diagnosed diabetes.Methods and resultsWe examined incidence rates of hospitalization for cardiovascular reasons and death among new patients with diabetes using the administrative health database of the nine million inhabitants of Lombardy followed from 2002 to 2007. Age and sex-adjusted rates were calculated and hazard ratios (HR) were estimated with a matched population without diabetes of the same sex, age (±1 year) and general practitioner.There were 158,426 patients with newly diagnosed diabetes and 314,115 subjects without diabetes. Mean follow-up was 33.0 months (SD ± 17.5). 9.7% of patients with diabetes were hospitalized for cardiovascular events vs. 5.4% of subjects without diabetes; mortality rate was higher in patients with diabetes (7.7% vs. 4.4%). The estimated probability of hospitalization during the follow up was higher in patients with diabetes than in subjects without for coronary heart disease (HR 1.4, 95% CI 1.3–1.4), cerebrovascular disease (HR 1.3.95% CI 1.2–1.3), heart failure (HR 1.4, 95% CI 1.3–1.4) as was mortality (HR 1.4, 95% CI 1.4–1.4).Younger patients with diabetes had a risk of death or hospital admission for cardio-cerebrovascular events similar to subjects without diabetes ten years older.ConclusionsThe elevated morbidity and mortality risks were clear since the onset of diabetes and rose over time. These data highlight the importance of prompt and comprehensive patients care in addition to anti-diabetic therapy in patients with newly diagnosed diabetes.