Elevated serum levels of the apoptosis related molecules TNF-α, Fas/Apo-1 and Bcl-2 in oral lichen planus

BACKGROUND: The serum circulatory levels of apoptosis related molecules measured in patients with oral lichen planus (OLP) and healthy individuals in order to investigate possible alterations associated with the clinical forms of OLP. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble Fas (sFas) and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in 13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects. RESULTS: Significantly elevated levels of TNF-alpha and sFas detected in OLP patients as compared with controls. Serum concentrations of Bcl-2 although increased in 17/26 patients, they were not statistically significant. Reticular OLP exhibited slightly elevated TNF-alpha and significantly elevated Bcl-2 serum levels, compared with erosive OLP. CONCLUSIONS: These data suggest that a putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive OLP may be associated with promotion of the disease activity.     

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.     

硬膜外腔阻滞对胸部手术应激反应的影响

目的 观察硬膜外腔阻滞对胸部手术应激激素和细胞因子的影响。方法20例食管癌手术病人,随机分为两组,每组10例,即全麻复令硬膜外腔阻滞(GEA)组和全麻(GA)组,分别测定麻醉诱导前、手术2h、手术4h、术毕、术后1d及术后3d的血浆去甲肾上腺素、肾上腺素、血清促肾上腺皮质激素(ACTH)、皮质醇、C-反应蛋白、IL-6及IL-10的水平。结果 血浆去甲肾上腺素和血清皮质醇GEA组术中术后无显著改变,但GA组术毕和术后1d显著升高(P<0.05),术后3d恢复至术前水平,组间比较前者有显著差异(P<0.05)。两组血浆肾上腺素、IL-10术中术后均无显著变化。两组血清ACTH、IL-6及CRP术中术后均显著升高(P<0.05),组间比较无显著差异。结论 硬膜外腔阻滞可以减轻胸部手术的应激反应。IL-6是较CRP更灵敏的反映组织损伤的炎性指标。     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

Comparison of Sputum and Serum Eosinophil Cationic Protein (ECP) Levels in Nonatopic Asthma and Chronic Obstructive Pulmonary Disease

The aim of the present study was to investigate whether sputum eosinophil cationic protein (ECP) concentrations could be a useful marker in the differential diagnosis between intrinsic asthma and chronic obstructive pulmonary disease (COPD). For this purpose total blood eosinophil counts were obtained and concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild attack and 9 COPD patients with acute exacerbation were measured by radioimmunoassay. Mean serum ECP concentration was 54.3 ± 23.0 g/L in the asthmatic group and 83.3 ± 79.2 g/L in the COPD group (p: n.s.). In the group of asthmatics mean sputum ECP level was 984.5 ± 1245.5 mg/L/g sputum and in the COPD group it was 417.5 ± 363.5 mg/L/g sputum. There was no significant difference in sputum ECP levels between patients with asthma and COPD. We conclude that neither sputum nor serum ECP levels are useful markers in differential diagnosis of asthma attack and acute exacerbation of COPD.     

Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a University Rheumatology clinic. The controls came from the same reference area. Subjects. Altogether 17 consecutive post-menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF-α; interleukin 1β, IL-1β; and interleukin-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load. Results. Pre-heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r_s=?0.63, P<0.05) and C-reactive protein (CRP) (r_s=?0.54, P<0.05) and close to significant for haptoglobin (r_s=?0.48, P=0.087) and IL-6 (r_s=?0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.     

Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils

BACKGROUND: Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. OBJECTIVE: The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. METHODS: RBL-2H3 cells were directly stimulated with anti-rat FcepsilonRI alpha-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human FcepsilonRI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). RESULTS: Cross-linking of FcepsilonRI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-FcepsilonRI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-FcepsilonRI mAb or by allergen in parallel. CONCLUSION: These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcepsilonRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.     

Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city.

AIM: To review the clinical experience of children and teens diagnosed with Type 2 diabetes (T2DM) at a paediatric hospital serving a large urban multi-ethnic population. METHODS: Retrospective chart review of patients with T2DM followed in the diabetes clinic at the Hospital for Sick Children (HSC) over an 8-year period. Patients who were included were younger than 18, referred at the onset of diabetes, and where presentation and/or clinical course was 'typical' of T2DM. RESULTS: Of 1020 children with diabetes followed at HSC, 4% were identified as having T2DM in 2002. There was a sixfold increase in new cases from 1994 to 2002. The mean age at diagnosis was 13.5 +/- 2.2 years (range 8.8-17.5) with a female-to-male ratio of 1.7. Most had a first- or second-degree relative with T2DM. There was an overrepresentation of children with T2DM from Asian and African Canadian ethnic groups relative to the regional population. The majority of teens were asymptomatic at presentation, with a smaller number in diabetic ketoacidosis (DKA) at diagnosis. Mean HbA1c at diagnosis was 10 +/- 3.4%. Approximately one half of patients were initially treated by diet and exercise with many requiring intensification of therapy over a short period of time. CONCLUSIONS: We report a similar increase in T2DM incidence and clinical presentation at HSC to other clinic reports in large North American urban centres. Of note is the high prevalence of children of South/South-East Asian descent.