二甲双胍和瑞格列奈对非肥胖的2型糖尿病患者非血糖性心血管危险标志的影响比较

在2型糖尿病患者中，反映炎症和内皮功能障碍的生物标志已经与心血管疾病和代谢调节联系起来。二甲双胍和促胰岛素分泌剂被证明有相同的抗高血糖作用。此研究比较了二甲双胍和促胰岛素分泌剂瑞格列奈在非肥胖的2型糖尿病患者的心血管疾病生物标志上的效能。     

Meningitis and midline facial deformity

A baby with unilateral cleft lip, midline cleft palate and hypertelorism developed meningitis in the first 48 h of life. Examination of the nasopharynx showed a soft tissue mass, which was confirmed as a basal encephalocele by computed tomography. There was also congenital hydrocephalus and the corpus callosum was absent. Surgical treatment included repair of the anterior basal skull defect, repair of the lip and palate, and ventriculo-peritoneal shunt. There is currently evidence of developmental delay and right-sided visual impairment due to Morning Glory syndrome. This case demonstrates that basal encephalocele should be considered in any baby with midline facial deformity who develops meningitis.     

Associations with medication adherence among ethnically different pediatric patients with renal transplants

This study examined perceived medication regimen characteristics as factors in levels of medication adherence among 26 African American and 42 European American pediatric renal transplant patients. Among both groups, perceived characteristics of their medication regimen, including pill size, pill taste and medication complexity, were found to have significantly low to moderate associations with medication adherence. These associations were stronger and more consistent across medication adherence measures among the African American patients. This supports the need to separately examine the factors contributing to medication adherence among ethnically different pediatric patients. Suggestions for promoting medication adherence among pediatric patients with renal transplants and implications for future research are discussed. Received: 21 September 2000 / Revised: 14 November 2001 / Accepted: 18 November 2001     

Palliative treatment of recurrent obstructing gastric cancer

Gallbladder perforation with loss of calculi in the abdomen is frequent during laparoscopic cholecystectomy and can cause serious late complications. We report on a 65-year-old woman who underwent laparoscopic cholecystectomy for gallbladder empyema, during which a stone spilled into the peritoneal cavity. The spilled gallstone was not noticed during the initial operation. Three months later, she reported left upper quadrant pain of recent onset without associated symptoms such as fever, nausea, or weight loss. On examination, a palpable 2-cm tender subcutaneous mass was found. Abdominal ultrasound demonstrated an incarcerated hernia, and computed tomography (CT) scan showed an intraperitoneal abscess located in the back of the anterior abdominal wall in the left upper quadrant, which contained a recalcification figure. The patient was brought to surgery, at which time an incision was made over the mass. A chronic abscess in the back of the abdominal wall, also spreading into the subfascial space, was drained, and purulent material was obtained with a large stone, 2.8 cm in diameter, which had become lodged in the rectus abdominis after an undetected stone spillage during laparoscopic cholecystectomy. The patient continued receiving antibiotic treatment for 7 days, recovered well, and was discharged 7 days after drainage of the abscess.     

Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite

Carcinogenic tobacco-specific nitrosamines are present in tobacco products and are believed to play a significant role in human cancers associated with tobacco use. Additional amounts of tobacco-specific nitrosamines could be formed endogenously. We tested this hypothesis by treating rats with nicotine and sodium nitrite and analyzing their urine. Initially, we treated groups of rats with (S)-nicotine (60 micromol/kg) and NaNO2 (180 micromol/kg), (S)-nicotine alone, NaNO2 alone or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 12 nmol/kg) by gavage twice daily for 4 days. We collected urine and analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol and its glucuronide. We did not detect these metabolites in the urine of rats treated with nicotine alone or nicotine plus NaNO2, indicating that endogenous conversion of nicotine to NNK did not occur. However, the urine did contain N'- nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'- nitrosoanatabine (NAT). Analysis of the (S)-nicotine used in this experiment demonstrated that it contained trace amounts of nornicotine, anabasine and anatabine. In a second experiment, we used an identical protocol to compare the endogenous nitrosation of this (S)-nicotine with that of synthetic (R,S)-nicotine, which did not contain detectable amounts of nornicotine, anabasine or anatabine. NNN (0.53 x 10(-3)% of nicotine dose), NAB (0.68%) and NAT (2.1%) were detected in the urine of the rats treated with the (S)-nicotine and NaNO2. NNN (0.47 x 10(- 3)% of dose), but not NAB or NAT, was present in the urine of the rats treated with synthetic (R,S)-nicotine and NaNO2. NNN probably formed via nitrosation of metabolically formed nornicotine. These results demonstrate for the first time that endogenous formation of tobacco- specific nitrosamines occurs in rats treated with tobacco alkaloids and NaNO2. The potential significance of the results with respect to nitrosamine formation in people who use tobacco products or nicotine replacement therapy is discussed.      

Expression of differential nitric oxide synthase isoforms in human normal gastric mucosa and gastric cancer tissue

The present study investigated the expression and distribution of three isoforms of nitric oxide synthase (NOS) in different anatomical regions of the human stomach and in gastric neoplastic tissues by immunohistochemistry using specific antibodies. Intracellular localization of individual isoenzymes of NOS was detected in normal gastric mucosa. Gastric cancer tissues had a marked reduction of all three NOS isoforms expression. The expression of the endothelial NOS, neuronal NOS and inducible NOS in the tumor tissue was significantly lower than in normal gastric mucosa (P = 0.01, P = 0.02, P < 0.01, respectively). In the tumor tissue the expression of inducible NOS was significantly lower than the expression of both constitutive forms of NOS (P < 0.01). There was a tendency to higher expression of both constitutive forms of NOS in earlier stages T2 of the tumor compared to advanced T4 tumor. In contrast, the expression of inducible NOS was higher than in the advanced T4 tumor than in the earlier stages T2 of the tumor. The mapping of the expression of endothelial NOS, neuronal NOS and inducible NOS in human stomach showed higher expression of NOS isoforms in the distal third than in the proximal third of the stomach (P = 0.03, P = 0.04, P = 0.01, respectively). We conclude that there is greater expression of NOS in the stomach corpus and in antrum than in the proximal third of the normal human stomach mirroring the anatomical predilection of common pathological changes in this part of the human stomach. Furthermore, there was loss of the expression of individual isoenzymes in gastric neoplasms.      

Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)- (+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha- (trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha- MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)- NNAL, respectively.      

MAGNOLOL REDUCES INFARCT SIZE AND SUPPRESSES VENTRICULAR ARRHYTHMIA IN RATS SUBJECTED TO CORONARY LIGATION

1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more potent than α-tocopherol in inhibiting lipid peroxidation in rat heart mitochondira. In the present study, the in vivo antiarrhythmic and anti-ischaemic effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague-Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10^?7, 10^?8 and 10^?9 g/kg, was adminstered intravenously 15 min before ligation of the coronary artery. 3. The incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the relief of coronary ligation were also reduced. 4. In rats subjected to 4h coronary ligation, 10^?7 and 10^?8 g/kg magnolol significantly reduced infarct size. 5. We conclude that magnolol may protect the myocardium against ischaemic injury and suppress ventricular arrhythmia during ischaemia and reperfusion.