Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: Protective effect of curcumin

The present study was designed to investigate the effect of CdCl₂-polluted drinking water (40 mg CdCl₂/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p < 0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd. Conclusion: Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-α-loaded nanoparticles

Aim: To study the in vitro release of recombinant human tumor necrosis factoralpha (rHuTNF-α) encapsulated in poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles, and investigate the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size. Methods: Three sizes (approximately 80, 170, and 240 nm) of PEGPHDCA nanoparticles loading rHuTNF-α were prepared at different MePEG molecular weights (Mr =2000, 5000, and 10 000) using the double emulsion method. The in vitro rHuTNF-α release was studied in PBS and rat plasma. Results: A higher burst-release and cumulative-release rate were observed for nanoparticles with higher MePEG molecular weight or smaller particle size. A decreased cumulative release of rHuTNF-α following the initial burst effect was found in PBS, while the particle sizes remained constant and MePEG liberated. In contrast, in rat plasma, slowly increased cumulative-release profiles were obtained after the burst effect. During a 5-h incubation in rat plasma, more than 50% of the PEGPHDCA nanoparticles degraded. Conclusion: The MePEG molecular weight and particle size had an obvious influence on rHuTNF-α release, rHuTNF-α released from PEG-PHDCA nanoparticles in a diffusion-based pattern in PBS, but in a diffusion and erosion-controlled manner in rat plasma.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Association between plasma paroxetine concentration and changes in plasma brain‐derived neurotrophic factor levels in patients with major depressive disorder

Recent studies have implicated brain‐derived neurotrophic factor (BDNF) in the pathophysiology of depression and in the activities of antidepressant drugs. Serum BDNF levels are lower in depressed patients and increase in response to antidepressant medications; however, no studies have examined the association between plasma concentrations of antidepressant drugs and plasma BDNF levels. We assessed plasma BDNF levels and paroxetine concentrations in 45 patients with major depression who were being treated with paroxetine. Plasma samples were collected between 10:00 h and 12:00 h at baseline and after 1, 2 and 6 weeks of treatment. The BDNF level and paroxetine concentration of each sample were measured via enzyme immunoassay and high‐performance liquid chromatography, respectively. Plasma BDNF levels increased after 2 and 6 weeks of paroxetine treatment. Plasma BDNF levels were significantly lower in men than in women. Changes in plasma BDNF level were correlated with plasma drug concentration after 2 (r = 0.309, p < 0.05) and 6 weeks (r = 0.329, p < 0.05) but not correlated with plasma drug concentration after 1 week (r = 0.284, ns). Multiple regression analysis confirmed that this change was only significantly correlated with plasma paroxetine concentration after 2 (standardised beta = 0.343, p < 0.05) and 6 weeks (standardised beta = 0.375, p < 0.05). These results suggest that paroxetine treatment increases plasma BDNF levels and that plasma paroxetine levels play an important role in changes in plasma BDNF levels.     

Effects of intensive insulin analogues therapy on function of pancreatic β-cell, inflammatory cells factor in the sulfonylurea secondary failure patients with type 2 diabetes mellitus

目的 观察胰岛素泵强化治疗对降糖药继发性失效(SFS)的2型糖尿病患者炎性细胞因子及胰岛功能的影响.方法 50例SFS的2型糖尿病患者停用口服降糖药,改用胰岛素泵强化治疗2周,观察治疗前后的空腹血糖、餐后2-h血糖、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平的变化.结果 强化治疗后,患者空腹血糖、餐后2-h血糖、HOMA-IR、TNF-α、IL-6水平均较治疗前明显下降(P＜0.05),HOMA-β较治疗前明显增高(P＜0.05).结论 胰岛素泵强化治疗可减轻SFS的2型糖尿病患者胰岛素抵抗,改善胰岛β细胞功能,降低机体炎性因子水平.     

Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes

ABSTRACT

Objective: To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycemic control.

Research design and methods: This study included a main treatment cohort (MTC) with 401 patients (HbA_1c?≥?7% and ≤10%) randomized and treated with oral saxagliptin 2.5, 5, or 10?mg once daily or placebo for 24 weeks and a separate open-label cohort (OLC) with 66 patients (HbA_1c?>?10% and ≤12%) who received saxagliptin 10?mg once daily for 24 weeks. Primary endpoint was HbA_1c change from baseline to week 24. Secondary endpoints included change from baseline to week 24?in fasting plasma glucose (FPG), proportion of patients achieving HbA_1c?<?7%, and changes in postprandial glucose area-under-the-curve (PPG-AUC). Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology.

Results: In the MTC, saxagliptin demonstrated statistically significant decreases in adjusted mean HbA_1c changes from baseline (mean, 7.9%) to week 24 (?0.43%, ?0.46%, ?0.54%) for saxagliptin 2.5, 5, and 10?mg, respectively, vs. +0.19% for placebo (all p?<?0.0001). Adjusted mean FPG was significantly reduced from baseline (?15, ?9, ?17?mg/dL) for saxagliptin 2.5, 5, and 10?mg, respectively, vs. +6?mg/dL for placebo (p?=?0.0002, p?=?0.0074, p?<?0.0001, respectively). More saxagliptin-treated patients achieved HbA_1c?<?7% at week 24 (35% [p?=?NS], 38% [p?=?0.0443], 41% [p?=?0.0133]) for saxagliptin 2.5, 5, and 10?mg, respectively, than placebo (24%). PPG-AUC was reduced for saxagliptin 2.5, 5, and 10?mg (?6868, ?6896, ?8084?mg·min/dL, respectively) vs. placebo (?647?mg·min/dL) with statistical significance demonstrated for saxagliptin 5?mg (p?=?0.0002) and 10?mg (p?<?0.0001). HbA_1c, FPG, and PPG-AUC reductions were also observed in the OLC at 24 weeks. In the MTC, adverse event frequency was similar across all study arms. No cases of confirmed hypoglycemia (symptoms, with fingerstick glucose ≤50?mg/dL) were observed in either cohort. Saxagliptin was not associated with weight gain. Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria, which limited the exposure time during which patients could remain on their originally randomized medication without the introduction of additional antihyperglycemic rescue treatment.

Conclusions: Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinically meaningful reductions in key parameters of glycemic control vs. placebo.

Trial Registration: Clinical Trials NCT00121641     

Serum levels of sFas and sFasL in subjects with type 2 diabetes — the impact of arterial hypertension

Aim

To evaluate the serum levels of sFas and sFasL in normotensive subjects with different degree of impairment of glucose tolerance as well as in type 2 diabetic patients with treated and treatment-naïve hypertension (AHT).

Material and methods

124 subjects (63 males and 61 females), of mean age 46,31±10,78 years are included in the study, divided in 5 age-matched groups: 19 subjects with type 2 diabetes (DM) and drug-controlled AHT; 30 subjects with type 2 DM and drug-naïve AHT; 30 normotensive subjects with type 2 DM; 26 normotensive subjects with prediabetes and 19 healthy controls. Serum sFas and sFasL levels are determined by highly sensitive enzyme immunoassay technique.

Results

No significant differences in sFas are observed among the studied groups. The levels of sFasL are decreased in normotensive subjects with type 2 DM (p<0,05), while subjects with prediabetes have intermediate values. In both hypertensive groups with DM sFasL levels are further decreased.

Conclusions

Serum sFas levels probably are not associated with the presence of impairment of glucose tolerance or AHT. Serum sFasL values tend to be decreased in subjects with impairment in glucose tolerance; further decrease is observed in hypertensive subjects with type 2 DM. Antihypertensive treatment does not influence the levels of sFasL.     

Inhibitory effects of nitric oxide and interleukin-10 on production of tumor necrosis factorα,interleukin-1β,and interleukin-6 in mouse alveolar macrophages

目的：观察一氧化氮和ＩＬ１０对肺泡巨噬细胞炎症反应的调节作用．方法：小鼠肺泡巨噬细胞（ＡＭ）受脂多糖（ＬＰＳ）１０ｍｇ·Ｌ－１刺激同时,加入一氧化氮合酶抑制剂Ｓ硫酸甲基异硫脲（ＳＭＴ）或一氧化氮供体Ｓ亚硝基乙酰青霉胺（ＳＮＡＰ）．ＥＬＩＳＡ法测定上清液中ＴＮＦα、ＩＬ１β、ＩＬ６和ＩＬ１０浓度．结果：ＡＭ受ＬＰＳ刺激后,ＴＮＦα、ＩＬ１β和ＩＬ６释放峰值分别在６、１２和２４小时．ＳＭＴ抑制一氧化氮释放,但促进ＩＬ１β和ＩＬ６释放,对ＴＮＦα无影响．ＳＮＡＰ对ＩＬ１β和ＩＬ６释放有明显的抑制作用,呈剂量依赖效应．重组ＩＬ１０抑制ＴＮＦα、ＩＬ１β和ＩＬ６释放,而ＩＬ１０单克隆抗体促进上述因子释放．结论：内源及外源性一氧化氮和ＩＬ１０均对ＬＰＳ诱导的炎症性细胞因子释放有抑制作用．     

Beta-blockers in the management of hypertension in patients with type 2 diabetes mellitus: is there a role?

It has been conclusively established that treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes mellitus will significantly reduce the incidence of stroke, heart failure and progression of diabetic complications. Beta-blockers are effective antihypertensive agents which, in long term studies, have proven beneficial in reducing important clinical end-points. However nonselective beta-blockers may have a negative effect on lipid profiles and contribute to hypoglycaemic unawareness, thus preventing their use in some patients with diabetes mellitus. The development of newer and more selective beta-blockers has overcome many of these problems. In addition, some of the newer agents have novel properties such as release of nitric oxide, which theoretically would make them more attractive in patients with diabetes mellitus. Overall, the adverse metabolic effects of beta-blockers do not appear to be important in clinical practice and these agents should no longer be contraindicated in patients with type 2 diabetes mellitus. Their proven cardiovascular benefits would seem to easily tip the balance in favour of their use.     

Impact of genetic polymorphisms of leptin and TNF-α on rosiglitazone response in Chinese patients with type 2 diabetes

Background  Leptin and tumor necrosis factor-α (TNF-α) play important role in homeostasis and insulin resistance in the treatment of Type 2 diabetes (T2DM). The aims of the present study were to investigate the association between leptin G-2548A and TNF-α G-308A polymorphisms and rosiglitazone response in T2DM patients. Materials  245 patients with T2D and 122 health volunteers were enrolled to identify leptin G-2548A and TNF-α G-308A genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two T2D patients with different leptin G-2548A and TNF-α G-308A genotypes received orally rosiglitazone as a single-agent therapy (4 mg day⁻¹ p.o.) for 12 weeks. Serum triglyceride (TG), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINs), glycated hemoglobin (HbAlc), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after rosiglitazone treatment. Results  A significant association between the variation of G-2548A allele with body mass index (BMI), serum leptin levels and FPG was observed in T2DM patients. Moreover, patients with G allele of leptin G-2548A had lower BMI and serum leptin concertration as well as bigger FPG than that in AA genotypes (P < 0.05). Moreover, we found an enhanced rosiglitazone effect in patients with AA genotype of leptin G-2548A on FINS and PINS compared with GG+GA genotype (P < 0.05). Finally, our results showed an attenuated rosiglitazone effect in patients with GA+AA genotype of TNF-α G-308A on FINS compared with GG genotype (P < 0.05). Conclusions  These data suggest there were not significantly differences in the frequencies of leptin G-2548A and TNF-α G-308A between patients with T2DM and health control. TNF-α G-308A polymorphism might be associated with the therapeutic efficacy of rosiglitazone in T2DM patients. This project was supported by the National Natural Science Foundation of China grant, No 30572230, and the Supported Program for New Century Excellent Talents in University sponsored by Ministry of Education of China, No. NCET-04-0749. Yang-Gen Lin and Jing-Wu these authors have contributed equally.     

Effect of endogenous nitric oxide on tumour necrosis factor-α-induced leukosequestration and IL-8 release in guinea-pigs airways in vivo

1. Tumour necrosis factor-α (TNF-α) is implicated in the pathogenesis of many pulmonary and airway diseases. TNF-α stimulation may release interleukin-8 (IL-8) in airways mediated via an increase in intracellular oxidant stress. In the present study, we have assessed leukosequestration and IL-8 release in the airways in response to intratracheal administration of human recombinant TNF-α, and examined the modulatory role of endogenous NO by pretreatment with a NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME).
2. TNF-α (10²–10⁴ u) was administered intratracheally in male guinea-pigs which were anaesthetized with urethane and were ventilated artificially. TNF-α induced a time- and dose-related increase in neutrophil numbers and a concomitant increase in human IL-8 equivalent level retrieved from bronchoalveolar lavage (BAL) with the peak effect at 10³ u at 6 h of TNF-α injection (late phase). Intratracheal administration of recombinant human (rh)IL-8 (0.025, 0.25, 2.5 ng) producing a similar range of human IL-8 equivalent levels in BAL as measured in our results induced neutrophil recovery in BAL fluid to a similar extent. Administration of anti-IL-8 antibody prevented the late phase of neutrophil recruitment induced by TNF-α or rhIL-8.
3. Pretreatment with L-NAME significantly enhanced the TNF-α (10³ u)-induced neutrophil recruitment and human IL-8 equivalents production at 6 h, but not at 1 h of TNF-α administration (early phase). L-Arginine reversed the responses to L-NAME. Pretreatment with 0.2% DMSO (i.v.) significantly inhibited TNF-α-induced neutrophil recruitment and human IL-8 equivalents release both in the early and late phase of the responses. Pretreatment with DMSO also inhibited the enhancement effect of L-NAME on the late phase of TNF-α-induced responses. DMSO failed to modify exogenous rhIL-8-induced neutrophil recruitment. Neither L-NAME nor DMSO alone induced any significant change in neutrophil numbers or human IL-8 equivalent level in BAL fluid.
4. Neutrophil depletion by cyclophosphamide pretreatment failed to modify TNF-α-induced human IL-8 equivalent release.
5. The expression of β2-integrin, CD11b/CD18 on neutrophils was increased only in the late but not early phase of TNF-α stimulation. L-NAME failed to modify these responses.
6. In conclusion, we demonstrated that NO may be an important endogenous inhibitor of TNF-α-induced leukocyte chemotaxis via inhibition of IL-8 production. Thus, the production of NO in airway inflammatory diseases may play a negative feedback role in self-limiting the magnitude of inflammatory responses.

     

Effect of long- and short-term treatments with pravastatin on diabetes mellitus and pancreatic fibrosis in the Otsuka–Long–Evans–Tokushima Fatty rat

Background and purpose:

The effects of statins on diabetes mellitus (DM) are controversial, and their effects on pancreatic fibrosis are poorly defined. We investigated the effect of long- and short-term treatments with pravastatin on the development of DM and pancreatic fibrosis in DM-prone Otsuka–Long–Evans–Tokushima Fatty (OLETF) rats.

Experimental approach:

Male OLETF rats were divided into four groups at 12 weeks of age. The first group received a standard rat diet until the end of the experimental period at age 80 weeks. The second group was given a diet containing 0.05% pravastatin from 12 weeks of age, before the onset of DM and pancreatic fibrosis, and the third group was given the same pravastatin diet from 28 weeks of age, after the onset of DM and pancreatic fibrosis, until age 80 weeks. The fourth group received the same pravastatin diet only for 16 weeks, from 12 to 28 weeks of age, and switched to a standard diet. Progressions of DM and pancreatic fibrosis were evaluated.

Key results:

Long-term treatments with pravastatin, either from 12 or 28 weeks of age, decreased serum glucose concentration and fibrotic area, elevated superoxide dismutase activity and down-regulated transforming growth factor-β1 mRNA in the pancreas. In contrast, after a short-term treatment with pravastatin, these parameters markedly deteriorated after its cessation.

Conclusions and implications:

The results suggest that long-term treatment with pravastatin improves DM and pancreatic fibrosis via anti-oxidative and anti-fibrotic properties, whereas cessation of pravastatin abolishes these beneficial effects, and accelerates DM and pancreatic fibrosis.     

Effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease

Objective: The effect of ₂-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. Methods: To evaluate the effect of ₂-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV₁/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl^–1), FEV₁ or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl^–1 and it increased after salbutamol by 0.1 mEq·dl^–1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl^–1) compared to the saline control (3.7 mEq · dl^–1) and salbutamol (3.6 mEq · dl^–1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV₁, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.     

Effect of inhibition of γ-glutamyltranspeptidase by AT-125 (Acivicin) on glutathione and cysteine levels in rat brain and plasma

Summary AT-125 (Acivicin) is an inhibitor of -glutamyltranspeptidase (-GTP) which initiates glutathione catabolism to cysteine. We measured plasma and brain glutathione and cysteine in rats treated with AT-125. Six h after AT-125 treatment, plasma glutathione had increased 6-fold and plasma cysteine had fallen significantly. Brain cysteine fell after 24 h of AT-125 treatment, and brain glutathione had also decreased 18%. AT-125 pretreatment inhibited brain uptake of ³⁵S when it was given as ³⁵S-GSH but had no effect when it was given as ³⁵S-cysteine. These results suggest that plasma glutathione is catabolized by -GTP, and cysteine derived from it is taken up by the brain. N-acetylcysteine was administered to AT-125 treated rats in an attempt to supply cysteine to the brain in the face of -GTP inhibition. N-acetylcysteine supported brain glutathione levels, suggesting that it can serve as a source of cysteine under these conditions.Abbreviations -GTP -glutamyltranspeptidase - GSH reduced glutathione - TCA trichloroacetic acid