Effects of the specific platelet-activating factor antagonists, BN 52021 and BN 52063, on various experimental gastrointestinal ulcerations

Platelet-activating factor (PAF) has been shown recently to induce gastrointestinal damage similar to that evoked by endotoxin, suggesting that the autacoid could be implicated in other types of gastrointestinal damage. Thus, the effects of BN 52021 and BN 52063, two specific PAF antagonists, were investigated in various experimental models of gastrointestinal damage in rats. BN 52021 and BN 52063, markedly reduced both the PAF- and endotoxin-induced alterations of the mucosa, suggesting a role for the autacoid in the latter process. BN 52021 and another unrelated PAF antagonist, triazolam, partially reduced the restraint-stress-induced gastric damage in young female, but not male, rats. Similar partial protection was obtained in rats with ethanol-induced gastric damage. In contrast with atropine and ranitidine, BN 52021 did not affect the gastric hypersecretion in pylorus-ligated rats nor the aspirin-induced gastric ulcerations. The present results indicate that PAF plays a major role in the gastric damage induced by endotoxin and may also partially contribute to the gastric lesions induced by ethanol and stress. The results suggest that there is a potential therapeutic use for PAF antagonists in certain types of gastrointestinal lesions in man.     

Identification of tumor-associated antigens and their purification for cyst fluids of ovarian epithelial neoplasms

Fifty patients with untreated cervical cancer were skin tested with a battery of recall antigens, and also sensitized and challenged with DNCB. A significant reduction of reaction to tuberculin, Varidase, and also DNCB was found in patients with stage III in comparison to healthy females of the same age group. Significant changes in immunoglobulin levels, an increase in IgA and a decrease in IgG, were observed in the cancer group. Serum lysozyme values were the same as in the control group.     

Therapy for acute pancreatitis with platelet-activating factor receptor antagonists

Acute pancreatitis （AP） causes release of platelet-activating factor （PAF）, which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor （PAF-R）. Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists （PAF-RAs） could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.     

What does remission tell us about women with eating disorders? Investigating applications of various remission definitions and their associations with quality of life

Objective

To compare remission rates, determine level of agreement and identify quality of life (QoL) distinctions across a broad spectrum of remission definitions among patients with eating disorders (ED).

Methods

Women (N = 195; 94 AN, 24 BN, and 77 EDNOS) from inpatient and partial hospital ED programs participated in a study of treatment outcomes. Remission rates were evaluated with percentages, kappa coefficients identified level of agreement and Mann–Whitney–Wilcoxon tests with Bonferroni corrections determined differences in quality of life between remitted and not remitted patients by remission definition.

Results

Depending on remission definition used, the percent of remitted patients varied from 13.2% to 40.5% for AN, 15.0% to 47.6% for BN and 24.2% to 53.1% for EDNOS. Several definitions demonstrated “very good” agreement across diagnoses. Remission was associated with higher quality of life in psychological, physical/cognitive, financial and work/school domains on a disease-specific measure, and in mental but not physical functioning on a generic measure.

Conclusions

Remission rates vary widely depending on the definition used; several definitions show strong agreement. Remission is associated with quality of life, and often approximates scores for women who do not have an eating disorder. The ED field would benefit from adopting uniform criteria, which would allow for more accurate comparison of remission rates across therapeutic interventions, treatment modalities and facilities. We recommend using the Bardone-Cone criteria because it includes assessment of psychological functioning, was found to be applicable across diagnoses, demonstrated good agreement, and was able to distinguish quality of life differences between remitted and not remitted patients.     

Medidas del rendimiento de modelos de predicción y marcadores pronósticos: evaluación de las predicciones y clasificaciones

Prediction models are becoming more and more important in medicine and cardiology. Nowadays, specific interest focuses on ways in which models can be improved using new prognostic markers. We aim to describe the similarities and differences between performance measures for prediction models. We analyzed data from 3264 subjects to predict 10-year risk of coronary heart disease according to age, systolic blood pressure, diabetes, and smoking. We specifically study the incremental value of adding high-density lipoprotein cholesterol to this model.We emphasize that we need to separate the evaluation of predictions, where traditional performance measures such as the area under the receiver operating characteristic curve and calibration are useful, from the evaluation of classifications, where various other statistics are now available, including the net reclassification index and net benefit.Full English text available from: www.revespcardiol.org     

Temporal sequence of comorbid alcohol use disorder and anorexia nervosa

Women with eating disorders have a significantly higher prevalence of substance use disorders than the general population. The goal of the current study was to assess the temporal pattern of comorbid anorexia nervosa (AN) and alcohol use disorder (AUD) and the impact this ordering has on symptomatology and associated features. Women were placed into one of three groups based on the presence or absence of comorbid AUD and the order of AN and AUD onset in those with both disorders: (1) AN Only, (2) AN First, and (3) AUD First. The groups were compared on psychological symptoms and personality characteristics often associated with AN, AUD, or both using general linear models. Twenty-one percent of women (n = 161) with AN reported a history of AUD with 115 reporting AN onset first and 35 reporting AUD onset first. Women with binge-eating and/or purging type AN were significantly more likely to have AUD. In general, differences were found only between women with AN Only and women with AN and AUD regardless of order of emergence. Women with AN and AUD had higher impulsivity scores and higher prevalence of depression and borderline personality disorder than women with AN Only. Women with AN First scored higher on traits commonly associated with AN, whereas women with comorbid AN and AUD displayed elevations in traits more commonly associated with AUD. Results do not indicate a distinct pattern of symptomatology in comorbid AN and AUD based on the temporal sequence of the disorders.     

BN大鼠用于评价中药注射液速发型过敏反应模型的建立及适用性评价

以清开灵注射液、双黄连注射液、黄芩苷、绿原酸为受试样本,以豚鼠为对照,通过观察BN大鼠(brown norway rats)过敏反应的特异性来建立中药注射液速发型过敏反应的动物模型,并对两者在评价中药注射液过敏反应中的适用性进行比较.本研究以中药注射液为致敏原,直接对BN大鼠进行致敏和攻击后,通过观察过敏症状、过敏反应率、过敏反应程度、组胺释放量、靶器官病变率和病变程度的变化,来评价BN大鼠过敏反应动物模型.结果显示中药注射剂致敏后,BN大鼠出现明显的过敏症状、血清和组织中组胺含量明显增加,肺组织和气管出现明显的病理改变,同时以青霉素和天花粉蛋白为阳性对照,也出现速发型过敏反应的表现;BN大鼠的过敏反应发生率、过敏反应程度、靶器官病变率和病变程度均显著高于豚鼠.试验结果说明BN大鼠为评价中药注射液过敏反应的适宜动物模型,且其敏感性高于豚鼠.     

Accuracy and cost comparison in medical testing using sequential testing strategies

The practice of sequential testing is followed by the evaluation of accuracy, but not by the evaluation of cost. This paper focuses on three logic rules for combining two sequences of tests: believe the positive (BP), which diagnoses disease if any of two tests is positive, believe the negative (BN), which diagnoses disease if any of two tests is negative, and believe the extreme (BE), which diagnoses disease if the first test is positive or, after a first inconclusive test, a second test is positive for disease. Comparisons of these strategies are provided in terms of accuracy using false positive rate, sensitivity pairs that make up the maximum receiver operating characteristic curve, and cost of testing, defined as the proportion of subjects needing two tests to diagnose disease. A method to incorporate the cost of testing into the definition of the optimal operating point is also presented. The performance of the testing strategies is examined with respect to the ratio of standard deviations and the correlation between test results under the bivariate normal assumptions. Under all parameter settings, the maximum receiver operating characteristic curve of the BE strategy never performed worse than the BN and BP strategies; the BE strategy also had the lowest cost. The use of body mass index and plasma glucose concentration to diagnose diabetes in Pima Indians was presented as a real-world application. The optimal operating points found by the BN and BE strategies produce lower false positive rate values than the BP strategy for these data.     

ASP3258, an orally active potent phosphodiesterase 4 inhibitor with low emetic activity

We investigated the pharmacology of a novel phosphodiesterase (PDE) 4 inhibitor, ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), comparing its potency with that of the most advanced PDE4 inhibitors, roflumilast and cilomilast. PDE4 inhibition by ASP3258 (IC(50)=0.28nM) was as potent as that achieved with roflumilast. ASP3258 inhibited lipopolysaccharide-induced tumor necrosis factor (TNF)-α production in rat whole blood cells (IC(50)=8.8 nM) and rat alveolar macrophages (IC(50)=2.6 nM). Orally administered ASP3258, roflumilast, and cilomilast dose-dependently inhibited production of interleukin-4, TNF-α, and cysteinyl leukotrienes, as well as leukocyte infiltration in bronchoalveolar lavage fluid from the airways of ovalbumin-sensitized Brown Norway rats, and these compounds showed almost complete inhibition at doses of 3, 3, and 30 mg/kg, respectively. PDE4 inhibitors induce emesis by mimicking the pharmacological action of α(2)-adrenoceptor antagonist. However, orally administered roflumilast (3mg/kg) and cilomilast (10mg/kg), but not ASP3258 (3mg/kg), inhibited α(2)-adrenoceptor agonist-induced anesthesia in rats and induced emesis in ferrets. Although ASP3258 (3mg/kg) inhibited airway inflammation completely, it had no emetic activity. As such, this compound may be useful in treating airway inflammatory diseases such as asthma and COPD.