2-(E)-(4-甲磺酰基)亚苄基环戊酮Mannich碱类化合物的合成及其抗炎活性

目的设计合成2-(E)-(4-甲磺酰基)亚苄基环戊酮Mannich碱类化合物,并对其抗炎活性进行初步评价.方法以环戊酮、4-甲磺酰基苯甲醛及胺类化合物为原料,经多步反应合成目标化合物,并以二甲苯致小鼠耳肿胀模型测试目标化合物的抗炎活性.结果与结论共合成10个新化合物,经1H-NMR和MS确证其结构.初步药理实验结果显示9个目标化合物均具有一定的抗炎活性.     

An Acute Myocardial Infarction Case that Survived An Out‐of‐Hospital Cardiac Arrest in Which Prominent Ischemic J Waves Were Documented

We describe a case of a myocardial infarction, in which prominent ischemic J waves were documented during recurrent ventricular fibrillation attacks. The patient was referred to our hospital to treat an out‐of hospital cardiac arrest. Although the 12‐lead electrocardiogram obtained just after the first cardioversion did not show any apparent J waves, a J wave‐like steep downsloping type ST‐segment elevation associated with q waves in the inferior leads was documented during multiple episodes of ventricular fibrillation. Our report revealed the appearance of J waves as an important marker for lethal arrhythmias in acute ischemia. (PACE 2012; 35:e27–e30)     

Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.     

Clinical outcome of retroperitoneal lymph node dissection after induction chemotherapy for metastatic non-seminomatous germ cell tumors

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) following induction chemotherapy has been considered a critical component in the comprehensive management of advanced non-seminomatous germ cell tumors (NSGCT). The objectives of the present study were to review the clinical outcome of patients who underwent RPLND and to evaluate the probability of necrosis alone, based on some readily available clinical data for these patients. METHODS: Forty-seven consecutive patients with NSGCT were treated with first-line chemotherapy at our institution between January 1993 and September 2002. Twenty-four of these patients, who underwent RPLND with normal values of tumor markers after induction chemotherapy, were included in the study. The cause-specific survival rate was calculated using the Kaplan-Meier method. Various predictive factors for the histology were analyzed using multivariate analysis. RESULTS: The pathological findings at resection were necrosis alone in 62.5% of cases, teratoma in 25.0%, and viable cancer in 12.5%. The cause-specific 3-year survival rate of patients who underwent complete and incomplete resection was 100% and 50.0%, respectively. Among several clinical factors, prechemotherapy tumor size less than 50 mm was found to be an independent predictor of necrosis alone (hazard ratio = 4.45, P= 0.04). CONCLUSION: Metastatic tumor size before chemotherapy appears to be one of the most important factors for the prediction of necrosis alone in the resected specimens of RPLND. The prognosis of patients might be influenced by the degree to which resection has been completed.     

Characteristics of obese children with low content of arachidonic acid in plasma lipids

BACKGROUND: Although there have been many studies on the relationship between obesity and long-chain polyunsaturated fatty acid (LCPUFA), the results and their interpretation are controversial, especially in children. Arachidonic acid (AA), the product of n-6 LCPUFA, is reported to be related to insulin resistance. The purpose of the present paper was to investigate the LCPUFA profile in obese children and mechanisms that contribute to reduced AA content. METHOD: An age- and sex-matched control study was performed. The study subjects were 59 obese children (mean age, 11.8 years) and 53 healthy non-obese children (mean age, 12.5 years). The study parameters included anthropometric measurements, serum lipids, leptin and fatty acid composition in plasma. RESULTS: Plasma fatty acids in obese children had lower linoleic acid (P < 0.0001) and higher dihomo-gamma-linolenic acid (P = 0.0004) than those in non-obese children. In all subjects combined, delta-6 desaturase (D6D) index (ratios of [C 18:3n-6+C 20:2n-6]/C 20:4n-6 or C 20:4n-6/C 18: 2n-6) correlated with leptin (P < 0.0001). There was no significant difference in AA content between obese and non-obese. However, the AA content was low (相似文献   

Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Hasegawa T, Okamoto A, Kamimura T, Tatsuno I, Hashikawa S‐N, Yabutani M, Matsumoto M, Yamada K, Isaka M, Minami M, Ohta M. Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients. APMIS 2010; 118: 167–78. Streptococcal toxic shock syndrome (STSS) is a re‐emerging infectious disease in Japan and many other developed countries. Epidemiological studies have revealed that the M1 serotype of Streptococcus pyogenes is the most dominant causative isolate of STSS. Recent characterization of M1 isolates revealed that the mutation of covS, one of the two‐component regulatory systems, plays an important role in STSS by altering protein expression. We analyzed the M1 S. pyogenes clinical isolates before or after 1990 in Japan, using two‐dimensional gel electrophoresis (2‐DE) and pulsed‐field gel electrophoresis (PFGE). PFGE profiles were different between the isolates before and after 1990. Markedly different profiles among isolates after 1990 from STSS and pharyngitis patients were detected. Sequence analysis of two‐component regulatory systems showed that covS mutations were detected not only in STSS but also in three pharyngitis isolates, in which proteins from the culture supernatant displayed the invasive type. The mutated CovS detected in the pharyngitis isolates had impaired function on the production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2‐DE. These results suggest that several covS mutations that lead to the malfunction of the CovS protein occurred even in pharyngeal infection.     

Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.