Nitric oxide-donating properties of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives.

1. The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. GEA 3162, GEA 3175, SIN-1 and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 microM, respectively). All four compounds induced a dose-dependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 microM) and inhibited 38-97% by oxyhaemoglobin (10-45 microM). 3. All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-1 and SNAP (100 microM) produced 50-70 microM NO2- + NO3- as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4. The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-1 and SNAP release nitric oxide.     

全膝关节置换翻修术的Meta分析

目的 通过对已报道的全膝关节置换翻修术文献进行总结分析,讨探膝关节置换翻修术前后的膝关节功能、翻修的主要原因、主要并发症及不同假体的术后疗效.方法 按照以下标准收集和分析有关全膝关节置换翻修术的文献:①1990年至2002年间发表,②报告患者数大于10例,③采用通用的膝关节评分标准.一名骨科专科医生独立收集数据,一名医学统计学专家独立采用Meta统计方法分析数据.结果 共有33 篇符合条件的文献被收集.患者共1356 例,其中男429例,女611例(部分文献性别分类数据缺失),平均年龄67岁(45～49岁),加权平均随访时间57个月( 6～108 个月),加权平均术前膝关节功能总评分为49 分(15～94分),术后为84分( 58～109分),全膝关节置换翻修术前后的总评分、功能评分、活动范围等有显著性提高,差异有统计学意义(总评分t=12.507,P<0.01, 功能评分t=4.704,P<0.01,活动范围:t=5.346,P< 0.01).全膝关节置换翻修术的原因主要是假体松动(55%),其它包括聚乙烯磨损(11%)、假体不稳(10%)、感染(7%).翻修术后的主要并发症仍然为假体松动(18%),其它包括假体不稳(16% )、感染(16% )、髌骨问题( 15% )及不明原因的膝关节疼痛(13%).髌骨问题包括髌骨脱位、半脱位、髌韧带撕裂、髌股关节疼痛等.结论 可以认为膝关节置换后翻修术是一种安全有效的手术.假体松动是膝关节置换翻新的主要原因和并发症.     

Screening of urinary tract abnormalities among day and nightwetting children

In order to detect possible urinary tract abnormalities among wetters, assessments of previous history completed by ultrasonography of the urinary tract and uroflowmetry were obtained for 145 wetting children and a random sample of 156 sex-matched non-wetting children drawn from a population of 3,375 seven-year-olds. Ultrasonography revealed abnormalities, including both morphological ones and cases with incomplete bladder emptying, in 5 out of 73 nightwetters (6.8%, 95% confidence limit, CL, 1.1-12.6), 10 out of 72 day and day and nightwetters (hereafter daywetters) (13.9%, CL 5.9-21.9) and 4 controls (2.6%, CL 0.1-5.0), the figure for the daywetters differing significantly from that for the controls (p less than 0.01). A fractioned voiding curve was recognized in 1 nightwetter (1.4%, CL -1.3-4.0), 7 daywetters (9.7%, CL 2.9-16.6) and 7 controls (4.5%, CL 1.2-7.7) the difference between the nightwetters and daywetters being significant (p less than 0.05). Depending on the previous history and abnormal findings in ultrasonography or uroflowmetry, examinations were continued with intravenous pyelography, voiding cystography, cystoscopy and/or by cystometry. Finally, marked structural or functional disorders of the urinary tract were detected in 11 out of 72 daywetters (15.3%, CL 7.0-23.6), 1 out of 73 pure nightwetters and 1 out of 156 control children. It is concluded that imaging of the urinary tract is not necessary for pure nightwetters, while ultrasonography or uroflowmetry and more sophisticated radiological or urological methods should be focused on those children with daytime wetting and clinical symptoms of voiding disturbances.     

Effects of antirheumatic drugs on leukotriene B4 and prostanoid synthesis in human polymorphonuclear leukocytes in vitro

The effects of D-penicillamine, sodium aurothiomalate, indomethacin, timegadine and tolfenamic acid on the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism were studied in human polymorphonuclear leukocytes (PMNs) in vitro. In short-term incubations, D-penicillamine and aurothiomalate did not affect leukotriene B4 (LTB4), prostaglandin E2 (PGE2) or thromboxane B2 (TXB2) production. Each of the three non-steroidal anti-inflammatory drugs (NSAIDs) used were potent inhibitors of prostanoid synthesis. In higher concentrations they also reduced LTB4 production; timegadine and tolfenamic acid were effective in concentrations comparable to those measured in plasma during drug therapy, whereas indomethacin was needed in ten times higher concentrations. The different effects of NSAIDs on 5-lipoxygenase activity may be of importance in their therapeutic actions as well as in the appearance of some side-effects, e.g. gastric irritation and "aspirin-induced" asthma.     

Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes

The aim of the present work was to study interactions between the synthesis of platelet-activating factor (PAF) and leukotriene B₄ (LTB₄) in human polymorphonuclear leukocytes (PMNs) in vitro. PAF, at nanomolar concentrations, stimulated calcium ionophore A23187-activated PMNs to release LTB₄ and 5-hydroxyeicosatetraenoic acid (5-HETE). This seems to be a receptor-mediated process as it was blocked by a PAF receptor antagonist WEB 2086 (IC₅₀ 6.6±3.9M). Moreover, LTB₄ stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alter PMN migration towards either LTB₄ or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB₄ is a concomitant event rather than a mediating process in LTB₄-induced chemotactic movement of PMNs. These effects are implicated in the complex network of interactions between inflammatory mediators that results accumulation and activation of PMNs in the exacerbation of inflammatory processes.     

The growth, development and education of Finnish twins: a longitudinal follow-up study in a birth cohort from pregnancy to nineteen years of age

The growth, development and vocation of 289 twins in a one year birth cohort beginning during pregnancy and followed up to the age of 19 years was compared with that of 11,623 singletons and two sets of controls matched either by maternal factors only or by these and perinatal morbidity, all from the same cohort. The twins were more often pre-term and small for their gestational age, and had more often suffered from perinatal asphyxia, neonatal hyperbilirubinaemia and hypoglycemia. They had learned to walk without support later than the singletons and the controls matched only by maternal factors, but this difference did not exist between the twins and the controls also matched by perinatal morbidity. The same kind of result was found when studying the number of words spoken at the age of one year and physical growth at the ages of 1 and 14 years. The twins did not differ significantly from the singletons during their compulsory nine years of primary and secondary schooling. According to the national registers of vocational choices, the twins had applied for admission to further education courses less often than the singletons or their controls matched only by maternal factors, but not when compared with the controls also matched by perinatal morbidity. Logistic regression analysis revealed numerous perinatal or environmental factors having an adverse effect on educational achievements, but the twin situation itself was not shown to have adverse effects. About half of the same-sex twin pairs and one seventh of the opposite-sex pairs had chosen the same vocation, compared with just over 10% similarity between the twins and their controls.     

Design and subjects of a Finnish epidemiological study on psychiatric disorders in childhood

In an epidemiological multi-centre study, parents filled in the Rutter Parent Questionnaire (RA2) and teachers filled in the Rutter Teacher Questionnaire (RB2) for almost 6000 children. The children filled in the Children's Depression Inventory (CDI). The subjects well represented the entire population of 8-9-year-old children in Finland. The material and design of the study as well as the basic demographic characteristics are presented.     

Persistent induction of nitric oxide synthase in tumours from mice treated with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid.

An anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) induced nitric oxide synthase (NOS) in the tumour, spleen, thymus and small intestine, but not in the lung, liver, kidney, heart or skeletal muscle in B6D2F1 mice bearing subcutaneous colon 38 tumours. This pattern of induction is distinct from that caused by agents such as endotoxin, muramyl dipeptide or Corynebacterium parvum. The induction of NOS (iNOS) in the tumour was more persistent (maximal at 3 days) than in other tissues (maximal at 12 h). Immunohistochemical staining suggested that iNOS was located in macrophages and endothelial cells within and around the tumour. Treatment with 5,6-MeXAA also caused substantial increases in plasma nitrite and nitrate (NOx) concentrations that peaked at 8-12 h after 5,6-MeXAA. The increase in plasma NOx was prevented by a NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), indicating that it was due to enhanced production of NO. Tumour-bearing mice were more responsive than controls to 5,6-MeXAA both in their plasma NOx increase and in their lower maximally tolerated dose. L-NIO was unable to prevent the complete tumour necrosis and regression caused by 5,6-MeXAA at a dose that substantially inhibited the increase of plasma NOx. In conclusion, the experimental anti-tumour agent 5,6-MeXAA induced NO synthesis in tumour-associated macrophages and in immunologically active tissues in parallel with its effects on tumour growth. The experiments with a non-selective NOS inhibitor L-NIO, however, suggest that NO is not a significant component in the mechanism of the anti-tumour action of 5,6-MeXAA in this particular model.     

Assessment of the Fundamental Flexural Guided Wave in Cortical Bone by an Ultrasonic Axial-Transmission Array Transducer

The fundamental flexural guided wave (FFGW), as modeled, for example, by the A0 Lamb mode, is a clinically useful indicator of cortical bone thickness. In the work described in this article, we tested so-called multiridge-based analysis, based on the crazy climber algorithm and short-time Fourier transform, for assessment of the FFGW component recorded by a clinical array transducer featuring a limited number of elements. Methods included numerical finite-element simulations and experiments in bone phantoms and human radius specimens (n = 41). The proposed approach enabled extraction of the FFGW component and determination of its group velocity. This group velocity was in good agreement with theoretical predictions and possessed reasonable sensitivity to cortical width (r² = 0.51, p < 0.001) in the in vitro experiments. It is expected that the proposed approach enables related clinical application. Further work is still needed to analyze in more detail the challenges related to the impact of the overlying soft tissue.