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.     

Schema-focused cognitive therapy for bipolar disorder: reducing vulnerability to relapse through attitudinal change

OBJECTIVE: Acceptance of, and adaptability to illness, are major determinants of adherence to treatment and functional recovery. This paper addresses the major psychosocial factors associated with bipolar disorder and the role of psychological interventions in symptom management and adaptability to the illness experience. A new model is presented highlighting the role of developmental experiences and temperament in determining reactions to bipolar disorder. The authors propose that by addressing reactions to the illness experiences and effects on self-concept through schema-focused cognitive therapy, functional recovery is more likely to occur among those patients functioning below expectation. METHOD: A systematic review of the current literature including an Index Medicus/MEDLINE search was conducted, focusing on risk factors, cognitive vulnerabilities and triggers associated with bipolar disorder. Psychological treatments available for the treatment of bipolar disorder are reviewed and details of a novel schema-focused cognitive model for this condition are presented. Traditional models of adaptation to chronic illness are outlined and incorporated into the proposed model. Schema-focused cognitive therapy is proposed as an approach to help patients reduce cognitive vulnerability to relapse in addition to adopting effective mood management strategies. RESULTS AND CONCLUSIONS: There is a need for psychological treatments which reduce the risks associated with poor functionality in patients with bipolar disorder. Schema-focused cognitive therapy specifically targets the temperament, developmental experiences and cognitive vulnerabilities that determine adjustment to illness. This proposed treatment, combined with pharmacotherapy, may offer new psychotherapeutic options for the future.     

Magnetic resonance spectroscopy and its applications in psychiatry

OBJECTIVE: This paper briefly describes neuroimaging using magnetic resonance spectroscopy (MRS) and provides a systematic review of its application to psychiatric disorders. METHOD: A literature review (Index Medicus/Medline) was carried out, as well as a review of other relevant papers and data known to the authors. RESULTS: Magnetic resonance spectroscopy is a complex and sophisticated neuroimaging technique that allows reliable and reproducible quantification of brain neurochemistry provided its limitations are respected. In some branches of medicine it is already used clinically, for instance, to diagnose tumours and in psychiatry its applications are gradually extending beyond research. Neurochemical changes have been found in a variety of brain regions in dementia, schizophrenia and affective disorders and promising discoveries have also been made in anxiety disorders. CONCLUSION: Magnetic resonance spectroscopy is a non-invasive investigative technique that has provided useful insights into the biochemical basis of many neuropsychiatric disorders. It allows direct measurement, in vivo, of medication levels within the brain and has made it possible to track the neurochemical changes that occur as a consequence of disease and ageing or in response to treatment. It is an extremely useful advance in neuroimaging technology and one that will undoubtedly have many clinical uses in the near future.     

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.