Anti-inflammatory effects of curcumin in a murine model of chronic asthma

BackgroundCurcumin, a dietary pigment responsible for the yellow colour of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects.MethodsForty-two BALB/c mice were divided into six groups: I, II, III, IV, V, and control group. All groups except the controls were sensitised and challenged with ovalbumin. Group I received nebulised saline in challenge period. Mice in groups II, III, IV, and V were administered curcumin at a dose of 10 mg/kg, curcumin 20 mg/kg, dexamethasone 1 mg/kg, and dimethyl sulfoxide 1 mg/kg, respectively, intraperitoneally once a day for the final 5 days of the challenge period. Animals were sacrificed 24 h after the last drug administration and the airway samples were evaluated histologically by light microscopy.ResultsAll histological parameters in Group III improved similar to Group IV when compared to Group I. In Group II, only thickness of epithelium was significantly lower compared with regard to Group I. All variables except epithelium thicknesses were found to be significantly better in Group III compared to Group II.ConclusionsIn our study, we demonstrated that curcumin administration alleviates the pathological changes of chronic asthma. Curcumin might be a promising therapy for asthma in the future.     

Beneficial effects of arginase inhibition and inhaled l-arginine administration on airway histology in a murine model of chronic asthma

BackgroundIncreased arginase activity in the airways induces reduced bioavailability of l-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled l-arginine and arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue.MethodsForty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled l-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA.Resultsl-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA.ConclusionWe demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.     

The effect of atorvastatin on lung histopathology in a murine model of chronic asthma

IntroductionAtorvastatin is a statin group medicine that reduces the level of serum cholesterol; thus it is used to treat hypercholesterolaemia. Independent of the cholesterol-lowering property of statins they also have anti-inflammatory and immunomodulating effects. This study aimed to investigate the effect of atorvastatin on histological changes in the lungs in a murine model of chronic asthma.Materials and methodsTwenty-eight BALB/c mice in Group I, II, III and IV were divided into four groups. All the mice except the control group (Group I) were sensitised with ovalbumin. Intraperitoneal injection with saline, atorvastatin (10 mg/kg), dexametazon (1 mg/kg) was administered to Group II, Group III, and Group IV respectively for five consecutive days. Mice were sacrificed 24 h after the last drug administration. All the histological properties of lung tissue samples from all groups were evaluated with light and electron microscopy. In addition, IL-4 and IL-5 levels of the lung tissue were measured.ResultsWhen Group II and Group III (atorvastatin) were compared, thicknesses of basement membrane and subepithelial smooth muscle layer, height of epithelium, number of mast and goblet cells were significantly lower in Group III. In comparing Group III (atorvastatin) and Group IV (dexamethasone), all the improvements in histological parameters were similar. In addition, the IL-4 and IL-5 levels of the lung tissue were significantly lower in atorvastatin group (Group III) compared to placebo-treated group.ConclusionAtorvastatin had a beneficial effect on histological changes in a chronic murine model of asthma.     

Efficacy of sulphasalazine on lung histopathology in a murine model of chronic asthma

Sulphasalazine is a specific inhibitor of nuclear factor kappa B (NF-kappa B) which plays a key role in asthma. To determine the impact of sulphasalazine in the treatment of chronic asthma, BALB/c mice were sensitized and challenged with ovalbumin. Mice with experimentally induced asthma in group I received saline, group II sulphasalazine 200 mg/kg, group III sulphasalazine 300 mg/kg, and group IV dexamethasone 1 mg/kg intraperitoneally once a day in the last 7 days of the challenge period. Histological findings of the airways were evaluated by light and electron microscopies. Dexamethasone and sulphasalazine in both doses significantly improved all airway histopathologic parameters of asthma except numbers of goblet cells. Both doses of sulphasalazine improved thicknesses of basement membrane better than dexamethasone. Dexamethasone reduced the number of mast cells better than sulphasalazine (200 mg/kg). Further studies are needed to evaluate the efficacy of sulphasalazine in the treatment of asthma.     

Inhaled Budesonide and Oral Dexamethasone Prevent Acute Mountain Sickness

BackgroundThis double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure.MethodsThere were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide (200 μg, twice a day [bid]), oral dexamethasone (4 mg, bid), or placebo (46 in each group). They traveled to 3900 m altitude from 400 m by car. Medication started 1 day before high-altitude exposure and continued until the third day of exposure. Primary outcome measure was the incidence of acute mountain sickness after exposure.ResultsOne hundred twenty-four subjects completed the study (42, 39, and 43 in the budesonide, dexamethasone, and placebo groups, respectively). Demographic characteristics were comparable among the 3 groups. After high-altitude exposure, significantly fewer participants in the budesonide (23.81%) and dexamethasone (30.77%) groups developed acute mountain sickness compared with participants receiving placebo (60.46%) (P = .0006 and P = .0071, respectively). Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation (SpO₂) than the placebo group at altitude. Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group. Four subjects in the dexamethasone group reported adverse reactions.ConclusionsBoth inhaled budesonide (200 μg, bid) and oral dexamethasone (4 mg, bid) were effective for the prevention of acute mountain sickness, especially its severe form, compared with placebo. Budesonide caused fewer adverse reactions than dexamethasone.     

Evaluation of coagulation and fibrinolytic parameters in adult onset GH deficiency and the effects of GH replacement therapy: a placebo controlled study

ObjectiveIncreased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency (GHD) because of its unfavorable cardiovascular risk profile. Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality. To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy (GHRT).Design-patientsNineteen patients with adult onset GHD were enrolled (twelve patients into the treatment and seven patients into the placebo group) into the study. Platelet count, collagen/epinephrine closure time, collagen/ADP closure time, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (AT III), protein C activity, protein S activity, lupus anticoagulant, antiphospholipid antibody immunoglobulin M, and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment.ResultsThe investigated parameters in the groups were similar at baseline except for low protein S (PS) activity. Protein S deficiency was observed in three of the patients in the GH treatment group at baseline, however the PS activity values normalized following GHRT. AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group.ConclusionsWe observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases, in other natural anticoagulants following GHRT. Further studies are required to understand the impact of these changes in cardiovascular morbidity and mortality in this patient population.     

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling,apoptosis of airway epithelial cells,and Th2 immune response in murine model of chronic asthma

Background and aimsIn previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma.MethodsTwenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50 mg/kg UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50 mg/kg UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone received the UDCA (50 mg/kg), UDCA (150 mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified.ResultsThe dose of 150 mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo.ConclusionsThese findings suggested that the dose of 150 mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.     

Effect of Dexamethasone on Myocardial Injury After Total Knee Arthroplasty: A Substudy of the Randomized Clinical DEX-2-TKA Trial

BackgroundMyocardial injury after noncardiac surgery (MINS) carries a high postoperative mortality. In this preplanned, subgroup analysis of the randomized DEX-2-TKA Trial, we investigated the effect of dexamethasone versus placebo on the concentration of cardiac troponin I and T (TnI and TnT) on the first postoperative morning after total knee arthroplasty. In addition, frequency of MINS, myocardial infarction, and major adverse cardiovascular events where evaluated.MethodsWe included 290 patients who received either 24 mg of dexamethasone intravenously (given perioperatively) or placebo. Blood samples were analyzed as either TnI or T depending on trial site.ResultsA total of 236 samples were eligible for analysis of TnI and 38 samples for TnT on the first postoperative morning. The median (IQR) TnI concentration was 4.6 ng/L (0-7.2 ng/L) in the dexamethasone group and 4.5ng/l (0-7.0 ng/L) in the placebo group (P = .96) on the first postoperative morning. The median TnT was 9 ng/L (6-11 ng/L) in the dexamethasone group and 8 ng/L (5-10 ng/L) in the placebo group (P = .68). The frequencies of MINS, myocardial infarction, and major adverse cardiovascular events were similar in the compared groups, but these analyses were underpowered.ConclusionWe found no effect of dexamethasone on postoperative concentration of troponin I or T on the first postoperative morning after total knee arthroplasty.     

Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT

BackgroundIsosorbide dinitrate combined with hydralazine therapy compared with placebo in patients with heart failure resulted in a sustained increase in left ventricular (LV) ejection fraction (EF) indicative of regression of LV remodeling in the first Vasodilator-Heart Failure Trial (V-HeFT-I) in patients receiving only digoxin and diuretic. In the African-American Heart Failure Trial (A-HeFT) a fixed-dose combination resulted in a 43% reduction in mortality in 1050 black patients with heart failure already treated with recommended neurohormonal inhibiting drugs. Whether the fixed-dose combination produces a further regression of LV remodeling when added to renin-angiotensin and sympathetic inhibitors has not been documented.Methods and ResultsEchocardiograms at baseline and 6 months after randomization to placebo or a fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) were analyzed in 678 A-HeFT participants in a core laboratory. LVEF rose by 2.8 EF units in the FDC I/H group versus 0.8% in the control group (P < .01), LV mass index fell by 7.4 g/m² in the FDC I/H group versus an increase of 1.4 g/m² in the placebo group (P < .05), LV diastolic transverse diameter fell by 2.2 mm in FDC I/H and was unchanged in placebo (P < .01), and the LV systolic and diastolic sphericity indices improved in the FDC I/H group but remained unchanged in the placebo group. The mean plasma B-type natriuretic peptide (BNP) also measured in a core laboratory fell in the FDC I/H group by 39 pg/mL compared with 8 pg/mL in the placebo group (P = .05).ConclusionsA fixed-dose combination of I/H produces regression of LV remodeling when added to background therapy with renin-angiotensin and sympathetic inhibitors in black patients with heart failure. This remodeling benefit may explain at least in part the mortality reduction in A-HeFT.     

Evaluation of airway responsiveness using colored three-dimensional analyses of a new forced oscillation technique in controlled asthmatic and nonasthmatic children

BackgroundBronchodilator response (BDR) is routinely used in asthma management. A new forced oscillation technique (FOT) is able to quickly measure respiratory system resistance (Rrs) and reactance (Xrs) at each tidal breath phase. The present study evaluated bronchial changes by using the new FOT.MethodsRespiratory resistance and reactance were measured using FOT in 132 children (age, 10.86±4.78 years; M:F=88:44), including asthmatic (n=98) and nonasthmatic children (n=34), pre- and post-bronchodilator inhalation in an asymptomatic state. Whole-breath or within-breath changes in Rrs and Xrs were measured and compared pre- and post-bronchodilator inhalation and between each group. All patients performed spirometry and forced expiratory nitric oxide pre- and post-bronchodilator inhalation.ResultsSpirometric parameters showed significant positive changes at V₅₀ and V₂₅ in both groups; however, these changes were not significantly different between the groups. eNO was significantly higher in the asthmatic group than in the nonasthmatic group; however, there was no significant change pre- and post-inhalation in either group. Rrs in the asthma group was significantly higher in the expiratory phase than in the inspiratory phase. Rrs and Xrs before and after bronchodilator inhalation were significantly different in the asthma group alone, except for the expiratory–inspiratory phase of each of these parameters. Changes in Rrs and Xrs at 5 Hz (R5 and X5) in a whole-breath and the inspiratory phase were significantly different between the groups.ConclusionsChanges in X5 and R5 reflect bronchial reversibility. The new FOT is useful for asthmatic children.     

Wound healing activity of aqueous extract of Crotalaria verrucosa in Wistar albino rats

ObjectiveTo evaluate the wound healing effect of aqueous extract of Crotalaria verrucosa (C. verrucosa) in rats.MethodsThree wound models including incision, excision and dead space wounds were used in this study. The parameters studied were breaking strength in incision models, granulation tissue dry weight, breaking strength and hydroxyproline content in dead space wounds, percentage of wound contraction and period of epithelialization in excision wound model.ResultsTwo doses of the extract with and without dexamethasone showed significant increases in mean hydroxyproline, total protein content and dry weight of granulation tissue but it was higher with dose 800 mg/kg comparing with the control. The dexamethasone treated group showed a significant (P<0.001) reduction in the wound breaking strength when compared to control group in incision type of wound model. Coadministration of C. verrucosa with dexamethasone significantly (P<0.001) increased the breaking strength compared to the dexamethasone treated only group. In excision wound model, the percentage of the wound contraction was significantly (P<0.01) increased by two doses of test extract on all the days except the lower dose which exhibited only on 12 th, 16 th days of drug treatment and it also reversed the dexamethasone suppressed wound contraction. It significantly (P <0.001) reduced the time required for epithelialization and reversed the epithelialization delaying effect of dexamethasone (P<0.001).ConclusionsC. verrucosa was found to possess significant wound healing property. This was evident by decrease in the period of epithelialization, increase in the rate of wound contraction, skin breaking strength, and granulation tissue dry weight content. Hence C. verrucosa could be a good wound healing agent.     

Peripheral airways involvement in children with asthma exacerbation

ObjectiveThe literature provides some evidence of peripheral airways key role in the pathogenesis of asthma. However, the extent to which lung periphery including acinar zone contribute to asthma activity and control in pediatric population is unclear. Therefore, the aim of the study was to estimate peripheral airways involvement in children with asthma exacerbation and stable asthma simultaneously via different pulmonary function tests.MethodsChildren with asthma exacerbation (n = 20) and stable asthma (n = 22) performed spirometry, body plethysmography, exhaled nitric oxide, impulse oscillometry (IOS), and multiple‐breath washout (MBW).ResultsPeripheral airway''s function indexes were increased in children with asthma, particularly in group with asthma exacerbation when compared with stable asthma group. The prevalence of abnormal results was significantly higher in asthma exacerbation. All children with asthma exacerbation had conductive ventilation inhomogeneity; 76% had acinar ventilation inhomogeneity. According to IOS measurements, resistance and reactance were within normal range, but other IOS parameters were significantly higher in children with asthma exacerbation compared with stable asthma group. The 36% of children with acute asthma had air trapping.ConclusionSignificant involvement of peripheral airways was observed in children with asthma, particularly in asthma exacerbation, which determine lung periphery as important additional target for therapy and provide new insights into pathophysiological process of pediatric asthma.     

Sinomenine ameliorates the airway remodelling,apoptosis of airway epithelial cells,and Th2 immune response in a murine model of chronic asthma

Background

Sinomenine (SIN), an alkaloid isolated from the root of Sinomenium acutum which has a variety of pharmacological effects, including anti-inflammation, immunosuppression and anti-angiogenesis. The present study aimed to evaluate the effects of SIN on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma.

Comparison of the Bronchodilative Effects of Salbutamol Delivered via Three Mesh Nebulizers in Children with Bronchial Asthma

BackgroundWe compared the bronchodilative effects of salbutamol delivered via 3 different mesh nebulizers, Aeroneb-go®(AE), Omron-NE-U22®(OM) and Pari-eMotion®(PA).MethodsWe enrolled 36 children with asthma who visited the Kurosaka Pediatrics and Allergy Clinic, randomly assigned to 3 groups for treatment with AE, OM or PA. The dose of salbutamol in the solution was 0.15 mg x body weight (kg) (minimum 2.5 mg, maximum 5 mg). FEVi, PEFR and V50 were measured in these patients before treatment, and at 15 and 30 minutes after salbutamol inhalation using one of the 3 mesh nebulizers.ResultsAll groups showed a significant improvement of FEVi, PEFR and V50 at 30 minutes after salbutamol inhalation. The AE group did not show a significant improvement in PEFR at 15 minutes after inhalation, whereas a significant improvement in FEVi and V50 was evident at the same time point. The OM group showed no significant improvement in V50 at 15 minutes after inhalation, whereas this group clearly showed a significant improvement in PEFR and FEVi at the same time point.ConclusionsOverall, all 3 mesh nebulizers were useful devices in treating bronchial asthma, although some differences in lung function improvement were evident. The limitation of this study is that subjects did not include patients with severe asthma attacks.     

Interaction of NPSR1 genotypes and probiotics in the manifestation of atopic eczema in early childhood

BackgroundNeuropeptide S Receptor (NPSR1) gene has been associated with multiple allergic phenotypes in several patient populations.ObjectiveWe analysed the effect of the NPSR1 genotypes in the development of asthma, rhinitis, eczema, or food allergy in children randomly receiving either probiotic or placebo treatment.Methods796 children born to families at high risk for allergic diseases were examined by a paediatrician at the age of three months, six months, two years, and five years. Asthma, rhinitis, eczema, and food allergy were diagnosed according to international guidelines. Treatment with probiotics (double-blinded and placebo controlled) was begun with mothers at 35 weeks of gestation age and continued after the birth of infants up to the age of six months. Association and additive inheritance models were used in genetic analyses.ResultsDistribution of the hopo546333 was suggestive in the group of patients with atopic eczema at two years. The hopo546333_G was found more often in those with eczema in the placebo group (p = 0.048, after Bonferroni correction) and the hopo546333_A was found more often in those with eczema and probiotics compared to those with eczema and placebo treatment. None of the NPSR1 tagging SNPs was associated with asthma, IgE-mediated asthma, or sensitisation. Allergic disease in both parents doubled the risk for IgE-mediated allergic disease (OR 2.1).ConclusionsThe NPSR1 gene SNP hopo546333 showed a suggestive association for high IgE-associated atopic eczema at two years.     

An Assessment of Change in Asthma Control among Adolescents and Adults with Persistent Asthma In Mometasone Furoate/Formoterol Fumarate Clinical Trials

Objective. This article provides evidence on the psychometric properties of the Asthma Control Questionnaire (ACQ) in adolescent and adult patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist (LABAs), and explores the factors associated with important improvements in asthma control. Methods. Data from patients in two large (n = 737 and 772) Phase III, randomized, double-blind, parallel-group, multi-center, placebo-controlled studies of mometasone furoate/formoterol fumarate (MF/F) combination formulation compared with monotherapies in subjects with persistent asthma previously treated with either low- or medium-dose inhaled glucocorticoids were used to evaluate the ACQ psychometric properties and predictors of important ACQ improvement, defined as an ACQ score decline from baseline of 0.5 or more at the end of treatment. Results. With 15% and 8% participation from adolescents in the low- and medium-dose studies, the ACQ yielded acceptable reliability (intraclass correlation coefficient ≥ 0.75), and baseline and change scores demonstrated moderate to strong correlations with other baseline measures and change scores in other measures of asthma-related health, including the Asthma Quality of Life Questionnaire (AQLQ12+) domains and total scores. More MF/F treatment group patients (48%) achieved an important ACQ change at 26 weeks compared with MF (32%), F (26%), and placebo (18%) treatment groups (p < .001). Use of rescue medications before randomization was a significant predictor of important ACQ improvement in both studies. Conclusions. These findings support the psychometric properties of the ACQ to measure asthma control among persistent asthma patients and provide confidence in the significant improvements in asthma control demonstrated by the MF/F treatment group.     

Efficacy of Pregabalin and Antioxidants Combination in Reducing Pain in Chronic Pancreatitis: A Double Blind Randomized Trial

Background

In patients with chronic pancreatitis (CP), pain relief is a dilemma. Antioxidants with pregabalin therapy have been reported to be useful. Hence, this study was carried out to determine the efficacy of the combination of antioxidant and pregabalin therapy in reducing pain in patients with CP.

Methods

This was a prospective, double blind, superiority, and randomized trial in patients with CP. The treatment group received pregabalin with antioxidants therapy for 8 weeks, and a similar placebo was administered to the controls. Primary outcome was to determine the change in maximum pain intensity assessed by visual analog scale (VAS) and Izbicki pain score. Secondary outcomes were the number of painful days, opioid and non-opioid requirements, improvement in quality of life, number of hospital admission, and overall patient satisfaction.

Results

A total of 90 patients were randomized to 45 in each arm. Demographic profile and baseline pain score were comparable. Patients in treatment group when compared to placebo group had a significant reduction in pain intensity (VAS score 2 ± 0.8 vs. 1.3 ± 0.9; p?=?0.007), non-opioid analgesic requirement in days (54.4±2.9 vs. 55.7±1.5; p?=?0.014), and number of hospital admissions (0.2 ± 0.5 vs. 0.6 ± 0.7; p?=?0.002), respectively. Significant proportion of patients was satisfied in the treatment group compared to placebo group (18% vs. 11%; p?=?0.03).

Conclusion

The combination of pregabalin and antioxidant significantly reduces the pain, requirement of non-opioid analgesics, and the number of hospital admissions in patients with CP. It also significantly improves the overall patient satisfaction.

Clinical Trials Register Number

CTRI/2017/05/008492.

     

Evaluation of effect of smoking and hypertension on serum lipid profile and oxidative stress

ObjectiveTo determine the effect of smoking, hypertension individually on lipid profile and lipid peroxidation and the cumulative influence of smoking and hypertension on oxidative stress and lipid profile.MethodsSerum total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides and malondialdehyde (MDA) were estimated in sixty cases including twenty smokers, twenty hypertensives, and twenty smokers with hypertension and compared with those in twenty age and sex matched healthy controls.ResultsStatistically significant increase in MDA, total cholesterol, LDL, VLDL and triglycerides and decrease in HDL in cases were observed in smokers, hypertensives and smokers with hypertension when compared to healthy controls. Smokers had significantly elevated levels of lipid profile and MDA except for HDL when compared to hypertensive group. Statistically significant increase in the levels of study parameters of smoking and hypertensive group was noticed when compared to group with hypertensives (P<0.05) and there was a statistically significant decrease in HDL levels in smoking and hypertensive group when compared to healthy controls. All the biochemical study parameters had larger effects (0.80<d<1.20) for the smoking and hypertensive group in comparison with control group.ConclusionsCigarette smoking, together with hypertension, has larger effect on lipid profile than in patients with cigarette smoking or hypertension alone and induces alteration in serum lipid levels and oxidative stress in the direction of increased risk for coronary artery disease.     

Efficacy and safety of tezepelumab in patients recruited in Japan who participated in the phase 3 NAVIGATOR study

BackgroundTezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan.MethodsNAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV₁) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed.ResultsOverall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV₁ was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was ?1.12 (0.15) and ?0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%).ConclusionsTezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.     

Effects of aldose reductase inhibitors on renal blood flow parameters in patients with early diabetic nephropathy

ObjectiveTo investigate the changes of renal blood flow parameters in patients with early-stage diabetic nephropathy (DN) treated with Aldose reductase inhibitors (ARI)/Epalrestat.MethodsIn this prospective, 120 early DN patients aged 20–75 years from the Endocrinology Department of Chengyang District People's Hospital of Qingdao City in 2015 were randomized to intervention group including 68 patients and control group including 52 patients. Two groups of patients separately received Epalrestat and placebo for 3 months. Renal vascular parameters and blood biochemical index were collected at baseline and after intervention.ResultsAfter 3 months of supplementation, Epalrestat significantly improved the renal and segmental renal arterial end-diastolic blood flow velocity (EDV) and the interlobular artery peak systolic blood flow velocity (PSV) compared with placebo. While Epalrestat markedly decreased the blood flow resistance index (RI) in interlobular artery compared to placebo. There were no significant changes in fasting blood glucose (FBG), diastolic blood pressure (DBP), systolic blood pressure (SBP), serum urinary acid (SUA), low-density lipoprotein cholesterol (LDL), triacylglycerol (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL), waist circumference (WC) and body mass index (BMI).ConclusionEpalrestat can effectively improve renal arterial blood flow and renal arterial perfusion, which play a protective role in early DN.