Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liver

Studies were carried out to investigate the metabolism of senecionine by human liver microsomes and the role of human cytochrome P450IIIA4 in this process. Human liver microsomes metabolized senecionine to two major products, (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and senecionine N-oxide. The rates of product formation (DHP and senecionine N-oxide) varied widely with the microsomal samples tested. There was a 30-fold difference in DHP formation and a 25-fold difference in N-oxidation between the poorest metabolizer and the highest metabolizer of senecionine. The conversion of senecionine to DHP and senecionine N-oxide in human liver microsomes was markedly inhibited by the mechanism-based inactivators of P450IIIA4, gestodene and triacetyloleandomycin. Anti-P450IIIA4 IgG, at a concentration of 1 mg/nmol of P450, was found to inhibit completely the formation of DHP and senecionine N-oxide in human liver microsomes (HL101) having low activity toward senecionine. At 5 mg IgG/nmol P450, anti-P450IIIA4 inhibited 90 and 84% respectively of the formation of DHP and senecionine N-oxide in liver microsomes (HL110) with the highest activity toward senecionine. The formation of DHP or senecionine N-oxide was highly correlated with the amount of P450IIIA4 measured in the microsomes using polyclonal anti-P450IIIA4 IgG. The rate of DHP production also had a strong correlation with the rate of senecionine N-oxide formation (r = 0.999) and with the rate of nifedipine oxidation (r = 0.998). Our present studies provide evidence that P450IIIA4 is the major enzyme catalyzing the bioactivation (DHP formation) and detoxication (senecionine N-oxide formation) of senecionine in human liver.     

Pain and faulty breathing: a pilot study

The purpose of this pilot study was to observe both relaxed and deep breathing patterns in a convenience sample to determine the incidence of normal versus faulty patterns of respiration. These observations were then combined with respondent answers to a survey on pain history to determine if there is any correlation between faulty breathing and musculo-skeletal pain patterns. If such a correlation can be made, then we propose that clinicians working with chronic pain patients may have improved outcomes if they address and correct faulty breathing patterns. Based on this study, it is suggested to include the evaluation and treatment of faulty respiration in the rehabilitation of chronic musculo-skeletal conditions, most notably cervical pain.     

Comparing reconstruction with ileocecal graft to jejunal interposition pouch after total gastrectomy in rats.

After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation.     

人工髋关节置换并发假体周围骨折的临床分析

[目的]分析人工髋关节置换术中、术后发生假体周围骨折的原因，探讨其预防措施和治疗方法。[方法]自1995年7月-2006年8月，共640例人工髋关节置换术患者，其中18例发生假体周围骨折，术中骨折11例（股骨距骨折7例，假体柄下端骨折4例），术后骨折7例（假体柄下端、远端骨折），男12例，女6例，年龄51-79岁，平均68岁，按照髋关节假体置换术后骨折的AAOS分型：I型1例，Ⅱ型4例，Ⅲ型4例，IVa型4例，IVb型2例，V型1例，Ⅵ型2例，其中术中假体周围骨折11例有10例予立即内固定，1例（Ⅱ型）股骨距劈裂骨折无明显移位未做内固定，仅延迟下地负重时间；术后假体周围骨折7例有4例在两周内行手术内固定，2例合并假体松动而采用全髋关节翻修术，1例（Ⅵ型）假体远端骨折因身体原因无法手术而采取保守治疗予以骨牵引4周后改石膏外固定。[结果]术后平均随访时间15．2个月（6-38个月），15例患者骨折均达到骨性愈合，2例发生骨折延迟愈合，保守治疗的1例患者术后6个月拍x线片示骨折畸形愈合，术后8个月因内科疾病死亡。Harris评分平均80分（67-92分）。[结论]术中暴力、股骨髓腔发育异常、假体型号过大、骨质疏松是术中假体周围骨折发生的主要原因，骨溶解、假体松动、骨质疏松加外伤是术后发生假体周围骨折的主要原因，根据不同分型采用不同的治疗方法以促进骨折愈合，稳定假体，减少卧床时间和并发症（尤其对高龄患者更为重要），尽早恢复功能。     

动态心电图对起搏器间歇性感知功能异常的诊断价值

目的 :探讨动态心电图检测对起搏器间歇性感知功能异常的诊断价值。方法 :采用MarquetteMars30 0 0动态心电图仪 ,对 36例 (4 9例次 )安装起搏器的患者进行随访 ,分析起搏、感知及与起搏器相关的心律失常。结果 :共检出起搏器间歇性感知功能异常 17例 (2 4例次 ) ,检出率为 4 7.2 % ,有 5例 (7例次 )合并两项感知异常。所有感知异常除 1例在常规心电图中检出外 ,其余 16例只在动态心电图中发现。检出与起搏器相关的心律失常 12例。根据动态心电图结果进行相应临床处理后 ,部分起搏器的感知功能异常消失。结论 :起搏器的感知功能异常多为间歇性的 ,动态心电图对间歇性感知异常的检出率较高 ,应是起搏器随访不可或缺的手段。     

一种鉴别免疫筛选噬菌体克隆真、假阳性的方法

目的探讨及早鉴别用免疫学方法筛选cDNA文库得到的阳性克隆是否真实可靠的方法.方法将阳性噬菌体克隆与宿主菌按一定的比例诱导培养后,取沉淀做SDS-PAGE后行W estern b lot;同时取出一个阳性克隆进行亚克隆,直至3次亚克隆均为全部阳性.结果3次亚克隆均为全部阳性的噬菌体克隆,在W estern b lot鉴定中也呈阳性反应.结论可用W estern b lot方法来鉴别用免疫学方法筛选cDNA文库得到的阳性克隆是否真实可靠.     

Proximal gastric vagotomy. A comparative study between the standard technique and the extended technique associated with denervation of the greater curvature

Forty-six patients in the postoperative period of proximal gastric vagotomy (PGV) for duodenal ulcer (DU) were studied comparatively to verify whether the dividing of the gastroepiploic nerves (Rosati's maneuver) can reduce or not the occurrence of recurrent ulcer as it was proposed. Twenty-one patients who underwent PGV associated with Rosati's maneuver (PGV-R) were compared to 25 after standard PGV (PGV-S), according to several criteria: (1) clinical evaluation; (2) pre and postoperative basal and pentagastrin-stimulated gastric acidity; (3) postoperative basal and pentagastrin-stimulated serum pepsinogen; (4) postoperative basal and sham feeding-stimulated serum gastrin; (5) postoperative endoscopy; (6) endoscopic Congo red test. Both groups were similar (P greater than 0.05) as to age, sex, levels of preoperative gastric acidity and had a 24.4 month average follow-up (12 to 58 months). There has been no significant difference between the techniques studied as to clinical, secretory, morphological or hormonal gastric tests, although PGV-R proved more effective in reducing basal gastric acidity than PGV-S (P less than 0.05). We concluded that Rosati's maneuver does not improve the results obtained with PGV, although it provided greater reduction of basal gastric acidity than PGV-S.     

中药煎剂保留灌肠治疗慢性结肠炎85例

目的:观察中药煎剂保留灌肠治疗慢性结肠炎的临床疗效。方法:对85例慢性结肠炎患者采用中药煎剂保留灌肠,同时服用654-2片治疗,观察临床症状和乙状结肠镜下的变化。结果:轻度41例,2个疗程治愈38例,3个疗程治愈3例;中度26例,3个疗程治愈24例;重度18例,3个疗程治愈8例,4个疗程治愈8例。痊愈率95.29%,总有效率100%。结论:中药煎剂保留灌肠治疗慢性结肠炎,疗效肯定,安全可靠。     

Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic pulmonary artery hypertension.

We describe the case of a pregnant woman with idiopathic pulmonary arterial hypertension, a responder in right heart catheterization, followed since the first trimester in outpatient consultations, admitted to hospital at 23 weeks gestation. She was treated with inhaled iloprost until delivery (at 34 weeks gestation) and continuous infusion of iloprost throughout the perioperative period and following days. This line of therapy has proved efficacious in previous cases. The authors present echocardiographic images that document acute changes in ventricular synchrony during inhalation of iloprost.