Effect of fluticasone 250 ��g/salmeterol 50 ��g and montelukast on exhaled nitric oxide in asthmatic patients

BACKGROUND:

Monitoring noninvasive biomarkers of inflammation is an important adjunct in asthma therapy.

OBJECTIVE:

The goal of the present study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in asthmatic patients, and to evaluate the NO response to maintenance fluticasone 250 μg/salmeterol 50 μg (F/S) and add-on montelukast 10 mg (M).

METHODS:

Thirty (24 women) nonsmoking, mild to moderate asthmatic patients were studied, mean age (± SD) 43±9 years, treated with F/S for more than one year. All were clinically stable for longer than eight weeks and had not taken oral corticosteroids and/or leukotriene antagonists for eight weeks before the present study. Spirometry, Juniper asthma symptom score, fractional exhaled NO (FENO) 100 mL/s, bronchial NO and alveolar NO concentration (CANO) were measured in a single-blind, nonrandomized crossover study.

PROTOCOL:

Visit 1: baseline F/S; visit 2: after four weeks of F/S plus M; visit 3: after four weeks of S plus M; and visit 4: after four weeks of S only. Values in asthmatic patients were also compared with 34 nonsmoking age-matched healthy controls with normal lung function.

RESULTS:

After 180 μg aerosolized metered dose inhaler albuterol, the forced expiratory volume in 1 s at baseline was 2.6±0.8 L (86%±16% of the predicted value) and the forced expiratory volume in 1 s over the forced vital capacity was 77%±9% (mean ± SD), and was similar at visits 2 to 4. Juniper scores were mildly abnormal at visits 1 to 3, but significantly worse (P=0.03) at visit 4 versus visits 1 to 3. FENO values at visits 1 to 3 were similar but significantly increased (P=0.007) at visit 4. Bronchial NO was higher (P=0.03) at visit 4, versus visits 1 and 2, and was no different at visit 3. Compared with the healthy subjects, FENO and bronchial NO values were abnormal (greater than the normal mean plus 2 SD) in 33% of asthmatic patients at visits 1 to 3. CANO was similar for visits 1 to 4. CANO was abnormal (greater than the normal mean + 2 SD) in 20% of asthmatic patients.

CONCLUSION:

In clinically stable asthmatic patients, despite controller treatment including moderate-dose inhaled corticosteroids and add-on M, 33% of mild to moderate asthmatic patients have ongoing nonsuppressed bronchial sites of increased NO production, compared with healthy control subjects. These controllers have no effect on CANO, which was abnormal in 20% of the asthmatic patients studied. The addition of add-on M to baseline moderate-dose inhaled corticosteroid did not further reduce total exhaled, bronchial and/or alveolar NO production.     

Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan

Purpose

Pegylated interferon (Peg-IFN)-based therapy is effective in treating chronic hepatitis B (CHB) and C (CHC) but frequently induces adverse events (AEs). This study was conducted to compare the incidence of Peg-IFN-based therapy-associated AEs in Taiwanese patients with CHB and CHC.

Methods

Fifty-six patients with CHB and 103 age-, sex- and treatment duration-matched patients with CHC were enrolled. Patients with CHB were treated with Peg-IFN-α-2a 180 μg/week for 24 weeks (HBeAg⁺, n = 31) or 48 weeks (HBeAg⁻, n = 25); patients with CHC were treated with Peg-IFN-α-2a 180 μg/week plus ribavirin 1,000–1,200 mg/day for 24 weeks (genotype 2/3, n = 57) or 48 weeks (genotype 1, n = 46).

Results

Significantly higher incidences of Peg-IFN-related AEs, especially neuropsychiatric symptoms, and ribavirin-associated skin manifestations were observed in patients with CHC compared with those with CHB, with either the 24- or 48-week regimen. Frequencies of laboratory abnormalities, except for anemia, were comparable in both groups. Neither group showed overt hepatic decompensation. Frequency of dose reduction was similar between the groups. Substantially higher rates of early termination and severe AEs were observed in patients with CHC.

Conclusions

Patients with CHB treated with Peg-IFN had fewer AEs than patients with CHC treated with Peg-IFN/ribavirin. All patients were treated safely.     

Serum levels of homocysteine in mice with malignant tumours

BACKGROUND:

Oxygen radicals and malondialdehyde (MDA) are tumourigenic. Homocysteine generates oxygen radicals. The possibility exists that hyperhomocysteinemia is a risk factor for cancer.

OBJECTIVE:

To investigate if serum levels of homocysteine and MDA are elevated in mice with malignant tumours.

METHODS:

Levels of serum homocysteine and MDA were estimated in 22 control and 22 tumour-bearing Balb/c mice.

RESULTS:

Serum homocysteine levels in control and tumour-bearing mice were 3.01±0.26 μmol/L and 4.05±0.46 μmol/L, respectively. The serum levels of MDA were 6.23±0.72 nmol/mL and 11.60±1.72 nmol/mL, respectively, in control and tumour-bearing mice.

CONCLUSION:

These results suggest that cancer in mice is associated with an increase in serum levels of homocysteine and the lipid peroxidation product MDA. It is, however, not known if this rise in homocysteine and MDA is due to cancer or if this rise causes cancer.     

A randomized controlled trial of two schedules of hepatitis B vaccination in predialysed chronic renal failure patients

Background

Patients with chronic renal disease should be vaccinated as soon as dialysis is forestalled, and this could improve the seroconversion of hepatitis B vaccination.

Objectives

In this study, we aimed to compare seroconversion and immune response rates using 4 doses of 40 μg and 3 doses of 20 μg Euvax B recombinant Hepatitis B surface Antigen (HBs Ag) vaccine administered to predialysis patients with chronic kidney disease (CKD).

Patients and Methods

In an open, randomized clinical trial, we compared seroconversion rates in 51 predialysis patients with mild and moderate chronic renal failure who received either 4 doses of 40 μg or 3 doses of 20 μg of Euvax B recombinant hepatitis B vaccine administered at 0, 1, 2, 6 and 0, 1, 6 months, respectively.

Results

Differences in seroconversion rates after 4 doses of 40 μg (80.88%) compared to 3 doses of 20 μg (92%) were not significant (P = 0.4124). The mean HBs antibody level after 4 doses of 40 μg at 0, 1, 2, and 6 months (182.2 ± 286.7) was significantly higher than that after 3 doses of 40 μg at 0,1, and 6 months (96.9 ± 192.1) (P = 0.004). Seroconversion after 4 doses of 40 μg (80.8%) was also significantly higher than that after 3 doses of 40 μg (77%) (P = 0.004). Multivariable analysis showed that none of the variables contributed to seroconversion.

Conclusions

We found that 4 doses of 40 μg did not lead to significantly more seroconversion than 3 doses of 20 μg.     

Salmeterol/Fluticasone Propionate versus Fluticasone Propionate Plus Montelukast

Introduction and objective

Asthma, owing to its chronic nature, is associated with a substantial economic burden. Healthcare providers need to compare the cost effectiveness of alternative asthma treatment options to ensure that they obtain the best value for money from the resources they control. The objective of the current study was to compare the cost effectiveness of salmeterol/fluticasone propionate in combination with fluticasone propionate plus montelukast in patients with symptomatic asthma uncontrolled with inhaled corticosteroid (ICS) monotherapy.

Study design and methods

Direct healthcare resource data were prospectively collected during a double-blind, randomized, 12-week clinical study of inhaled salmeterol/fluticasone propionate 50/100µg twice daily (n = 356) and inhaled fluticasone propionate 100µg twice daily plus oral montelukast 10mg daily (n = 369). Resources were costed in Dutch guilders (NLG) from the perspective of The Netherlands healthcare system using 1999/2000 prices, but have been presented in US dollars and euros. The primary effectiveness measure was the proportion of successfully treated weeks (based on mean morning PEF values). Secondary measures were episode-free days, symptom-free days, and symptom-free nights.

Results

Salmeterol/fluticasone propionate was more effective than fluticasone propionate plus montelukast as measured by the proportion of successfully treated weeks mean 63.3% vs 39.0%; median difference 25%; p < 0.001). Salmeterol/fluticasone propionate was also more effective than fluticasone propionate plus montelukast according to the secondary effectiveness measures. The mean total direct daily healthcare costs per patient were 16% higher with fluticasone propionate plus montelukast than with salmeterol/fluticasone propionate mainly due to higher drug costs in the former group ($US2.25 vs 1.94; € 1.92 vs 1.66, respectively; the NLG was fixed against the euro at a rate of €1 = NLG2.2 on 31 December 1998; $US1 = NLG1.883, June 2003; $US1 = €0.848, June 2003). Incremental cost-effectiveness analyses showed that salmeterol/fluticasone propionate was dominant over fluticasone propionate plus montelukast and sensitivity analyses showed these results to be robust.

Conclusion

Salmeterol/fluticasone propionate is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with symptomatic asthma uncontrolled by ICS.

     

Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy

Summary

Background

Accurate prediction of prognosis in idiopathic membranous nephropathy (iMN) allows restriction of immunosuppressive therapy to patients at high risk for ESRD. Here we re-evaluate urinary low-molecular-weight proteins as prognostic markers and explore causes of misclassification.

Design, setting, participants, & measurements

In a cohort of 129 patients with serum creatinine concentration <135 μmol/L and proteinuria ≥3.0 g/10 mmol, urinary α1- (uα1m) and β2-microglobulin (uβ2m) excretion rate was determined. Urinary α1m and uβ2m-creatinine ratio was also obtained. We defined progression as a rise in serum creatinine ≥50% or ≥25% and an absolute level ≥135 μmol/L.

Results

Median survival time was 25 months, and 47% of patients showed progression. The area under the receiver operating characteristic curve for uβ2m was 0.81 (95% CI: 0.73 to 0.89). Using a threshold value of 1.0 μg/min, sensitivity and specificity were 73% and 75%, respectively. Similar accuracy was observed for the uβ2m-creatinine ratio with sensitivity and specificity of 75% and 73%, respectively, at a threshold of 1.0 μg/10 mmol creatinine. Similar accuracy was found for uα1m and uα1m-creatinine ratio. Blood Pressure and cholesterol contributed to misclassification. Repeated measurements improved accuracy in patients with persistent proteinuria: the positive predictive value of uβ2m increased from 72% to 89% and the negative predictive value from 76% to 100%.

Conclusions

Urinary excretion of uα2m and uβ2m predict prognosis in iMN. A spot urine sample can be used instead of a timed sample. A repeated measurement after 6 to 12 months increases prognostic accuracy.     

Asthma control score based on filled medication prescriptions: A validation study

BACKGROUND:

Periodic measurement of disease control is recommended to characterize asthma and monitor treatment.

OBJECTIVE:

To elaborate and validate an asthma control score (ACS) for use in studies based on administrative health databases.

METHODS:

Adult patients with asthma were recruited from a clinic. The ACS is based on the average number of doses of short-acting inhaled beta₂-agonists taken per week and short courses of oral corticosteroids dispensed over a three-month period. Data were obtained from the Régie de l’assurance maladie du Québec database in Canada. The ACS was compared with the asthma control questionnaire and the use of health care services for asthma over a 12-month period.

RESULTS:

A total of 60 patients were enrolled. They had a mean (± SD) age of 50.4±13.9 years, and 43.3% were male. Patients had had asthma for 20.8±15.1 years on average and had a mean prebronchodilator forced expiratory volume in 1 s of 77.0% of the predicted value. The mean ACS was 8.3±11.6, with a range of 0 to 60. The ACS was not found to be correlated with the asthma control questionnaire, but it was significantly associated with health care services used. For each additional point in the ACS, patients were 2% more likely to need acute care for asthma (rate ratio 1.02; P=0.02).

CONCLUSIONS:

Further studies including patients followed by general practitioners are required before the general use of this score. This innovative score is useful to rapidly assess the control of asthma over long periods of time and at a low cost in studies using administrative drug databases.     

Ventricular pacing thresholds following high-energy implantable cardioverter defibrillator shocks in integrated bipolar defibrillation systems

BACKGROUND:

Increased ventricular pacing thresholds have been observed following monophasic implantable cardioverter defibrillator (ICD) shocks.

AIM:

To examine changes following high-energy biphasic shocks delivered by integrated bipolar ICD systems.

METHOD:

Ten episodes of ventricular fibrillation (VF) were induced at 10 min intervals in nine pigs with integrated ICD systems. After 10 s of each episode of VF, a 40 J biphasic shock was delivered, which successfully terminated VF (a total of 10 shocks). The bipolar pacing threshold at the right ventricular apex was measured before each shock and at 1 min intervals after each shock.

RESULTS:

The mean pacing threshold was 0.029±0.059 μJ before the first shock and gradually increased to 0.14±0.10 μJ after the 10th shock.

CONCLUSION:

It may be necessary to pace at a high-voltage output following biphasic shocks delivered by integrated bipolar ICD systems.     

Plasma nitric oxide metabolite levels increase during successive exercise stress testing – A link to delayed ischemic preconditioning?

BACKGROUND:

Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning.

OBJECTIVES:

To determine whether plasma nitrates and nitrites (NO_x⁻, as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement

METHODS:

Twenty-two patients with ischemic heart disease each performed two effort tests at 24-h intervals. Plasma NO_x⁻ level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical endpoints and were compared between the two tests.

RESULTS:

Plasma NO_x⁻increased slightly after the first exercise test compared with pretest value (17.05±1.6 μmol/mL versus 15.38±1.4 μmol/mL). In turn, after the second test there was a significant rise in NO_x⁻ level (23.65±2.2 μmol/mL versus 15.10±1.3 μmol/mL, P<0.03). The pretest values were almost identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although ischemic stress was the same, ST depression was significantly lower (P<0.01) for the second test (0.85±0.06 mm versus 1.73±0.16 mm).

CONCLUSION:

Our study shows an increased plasma NO_x⁻level after the second of two consecutive exercise stress tests at 24-h intervals, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as a trigger and effector of ischemic preconditioning.     

Effects of chromium malate on glycometabolism,glycometabolism‐related enzyme levels and lipid metabolism in type 2 diabetic rats: A dose–response and curative effects study

Aims/Introduction

The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzyme levels and lipid metabolism in type 2 diabetic rats, and dose–response and curative effects.

Materials and Methods

The model of type 2 diabetes rats was developed, and daily treatment with chromium malate was given for 4 weeks. A rat enzyme-linked immunosorbent assay kit was used to assay glycometabolism, glycometabolism-related enzyme levels and lipid metabolism changes.

Results

The results showed that the antihyperglycemic activity increased with administration of chromium malate in a dose–dependent manner. The serum insulin level, insulin resistance index and C-peptide level of the chromium malate groups at a dose of 17.5, 20.0 and 20.8 μg chromium/kg bodyweight were significantly lower than that of the model, chromium trichloride and chromium picolinate groups. The hepatic glycogen, glucose-6-phosphate dehydrogenase and glucokinase levels of the chromium malate groups at a dose of 17.5, 20.0 and 20.8 μg chromium/kg bodyweight were significantly higher than that of the model, chromium trichloride and chromium picolinate groups. Chromium malate at a dose of 20.0 and 20.8 μg chromium/kg bodyweight significantly changed the total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides levels compared with the chromium trichloride and chromium picolinate groups.

Conclusions

The results showed that chromium malate exhibits greater benefits in treating type 2 diabetes, and the curative effect of chromium malate is superior to chromium trichloride and chromium picolinate.     

Prevention of contrast-induced nephropathy: A randomized controlled trial of sodium bicarbonate and N-acetylcysteine

BACKGROUND:

Contrast-induced nephropathy (CIN) continues to be a common cause of acute renal failure in high-risk patients undergoing radiocontrast studies. However, there is still a lack of consensus regarding the most effective measures to prevent CIN.

METHODS:

One hundred eighteen patients with diabetes mellitus and/or renal insufficiency, scheduled for coronary angiography or intervention, were randomly assigned to one of four treatment groups: intravenous (IV) 0.9% NaCl alone, IV 0.9% NaCl plus N-acetylcysteine (NAC), IV 0.9% sodium bicarbonate (NaHCO₃) alone or IV 0.9% NaHCO₃ plus NAC. All patients received IV hydration as a preprocedure bolus and as maintenance. Iso-osmolar contrast was used in all patients. CIN was defined as an increase of greater than 25% in the serum creatinine concentration from baseline to 72 h.

RESULTS:

The overall incidence of CIN was 6%. There was no statistically significant difference in the incidence of CIN among the groups. There was a CIN incidence of 7% in the NaCl only group, 5% in the NaCl/NAC group, 11% in the NaHCO₃ only group and 4% in the NaHCO₃/NAC group (P=0.86). The maximum increase in serum creatinine was 14.14±12.38 μmol/L in the NaHCO₃ group, 10.60±29.14 μmol/L in the NaCl only group, 9.72±13.26 μmol/L in the NaCl/NAC group and 0.177±15.91 μmol/L for the NaHCO₃/NAC group (P=0.0792).

CONCLUSION:

CIN in high-risk patients may be effectively minimized solely through the use of an aggressive hydration protocol and an iso-osmolar contrast agent. The addition of NaHCO₃ and/or NAC did not have an effect on the incidence of CIN.     

Phase II,randomized, open,controlled study of AS03‐adjuvanted H5N1 pre‐pandemic influenza vaccine in children aged 3 to 9 years: follow‐up of safety and immunogenicity persistence at 24 months post‐vaccination

Background

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years.

Methods

In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3–9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03_A or AS03_B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. ({"type":"clinical-trial","attrs":{"text":"NCT00502593","term_id":"NCT00502593"}}NCT00502593).

Results

The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4⁺ T cells with a T_H1 profile were observed.

Conclusions

Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.     

Linking soluble vascular adhesion molecule-1 level to calcific aortic stenosis in patients with coronary artery disease

BACKGROUND:

Calcific aortic stenosis (AS) is an atherosclerosis-related process and the most common cause of valve disease requiring surgery.

OBJECTIVE:

To assess the association of inflammatory markers with AS in advanced atherosclerosis.

METHODS:

Consecutive patients with coronary artery disease (CAD) associated with AS were prospectively identified (mean transvalvular aortic gradient of 30 mmHg or greater). Subjects with aortic sclerosis (mean transvalvular aortic gradient of 10 mmHg or less) served as controls. All patients underwent clinical evaluation, echocardiography and coronary angiography.

RESULTS:

One hundred twenty-two patients with AS (85 men) and 101 with aortic sclerosis (76 men) of similar CAD severity were enrolled. The AS patients were older (mean [± SD] 71±7 years versus 66±7 years; P<0.001), had higher soluble vascular adhesion molecule-1 (s-VCAM-1) levels (1533±650 μg/L versus 1157±507 μg/L; P<0.001), but lower soluble intercellular adhesion molecule-1 (s-ICAM-1) (254±81 μg/L versus 293±84 μg/L; P<0.01) and soluble E-selectin (53±28 μg/L versus 62±29 μg/L; P<0.05) levels. The two groups did not differ with respect to C-reactive protein level (3±2.9 mg/L versus 3.4±2.6 mg/L; P not significant). Higher s-VCAM-1 (OR 1.09, 95% CI 1.04 to 1.14; P<0.001) and lower s-ICAM-1 (OR 0.82, 95% CI 0.72 to 0.94; P<0.001) levels were associated with AS after adjustment for age.

CONCLUSION:

Increased s-VCAM-1 levels were associated with calcific AS in patients with significant CAD.     

Renal effects of long-term treatment with 5-aminosalicylic acid

BACKGROUND:

A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD).

OBJECTIVE:

To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD.

METHODS:

A retrospective analysis of 171 consecutive outpatients with Crohn’s disease or ulcerative colitis was conducted. Serum creati-nine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate.

RESULTS:

In 171 patients (93 women, 78 men), the mean (± SD) dose of 5-ASA was 3.65±0.85 g/day with a cumulative dose of 11±7.7 kg over an interval of 8.4±5.9 years. Serum creatinine concentrations increased from 76.8 μmol/L to 88.7 μmol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2±4.5, 12.3±8.7 and 11.2±6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=−0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=−0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034).

CONCLUSION:

The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.     

Increased cytokine/chemokines in serum from asthmatic and non‐asthmatic patients with viral respiratory infection

Background

Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients.

Objectives

The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles.

Patients/Methods

Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses.

Results

Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients.

Conclusions

Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.     

Edaravone reduces mitochondrial damage due to reperfusion injury following leg ischemia in rats

PURPOSE:

Free radicals have been implicated in reperfusion injury. It was shown that the free radical scavenger edaravone might suppress reperfusion injury in rat extremities. The present study aimed to elucidate how edaravone suppresses reperfusion injury, focusing on its effect on the mitochondrial structure and glycogen storage in the lower extremity muscles.

METHODS:

Sixteen male Lewis rats (mean [± SD] weight 497±32 g) were divided into two groups and injected with either 3.0 mg/kg of edaravone (edaravone group, n=8 rats) or the same dose of saline (control group, n=8 rats) into the peritoneal cavity. The rat reperfusion injury models were created by clamping the bilateral common femoral arteries for 5 h, then declamping. The muscles were harvested more than 5 h after the start of reperfusion. The mitochondrial damage, defined as mitochondrial swelling, was examined using a transmission electron microscope at ×30,000 original magnification (n=3 for each rat). Glycogen storage, defined as a positive periodic acid-Schiff stain area, was examined using computerized densitometry (n=5 sections for each rat).

RESULTS:

The mitochondria in the control group demonstrated marked swelling (mean mitochondrial size = 0.169±0.059 μm²). However, the mitochondria in the edaravone group had significantly less swelling (mean mitochondrial size = 0.102±0.036 μm²; P<0.01). The mean percentage of positive periodic acid-Schiff stain was also significantly higher in the edaravone group than in the control group (51.7±6.8% versus 7.3±2.1%; P<0.01).

CONCLUSION:

The results suggested that edaravone reduces mitochondrial damage due to reperfusion injury, resulting in a high level of glycogen storage.     

The Efficacy and Safety of Peginterferon-α-2a in Korean Patients with Chronic Hepatitis B: A Multicenter Study Conducted in a Real Clinical Setting

Background/Aims

Genotype C is the principal type of hepatitis B virus (HBV) in Koreans and is associated with poor prognosis for peginterferon α-2a therapy. The efficacy of and compliance to peginterferon α-2a therapy were investigated in Koreans with hepatitis B in a real clinical setting.

Methods

Hepatitis B patients treated with peginterferon α-2a from 2008 to 2011 at four university hospitals were consecutively enrolled.

Results

Eighty-eight patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean treatment period was 36.1±15.2 weeks. In 26.1% of patients, treatment was discontinued due to insufficient antiviral effects and adverse events. At 24 weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV DNA suppression to <2,000 IU/mL and HBeAg loss/seroconversion. For HBeAg-negative patients, 10/13 (76.9%) achieved HBV DNA suppression to <2,000 IU/mL at 24 weeks after treatment. During the follow-up period, 15 (30.6%) of the 49 patients who achieved HBV DNA suppression to 2,000 IU/mL developed a breakthrough HBV DNA level of >2×10⁶ IU/mL.

Conclusions

Peginterferon α-2a therapy in Koreans with hepatitis B in a real clinical setting resulted in a lower virologic response, as compared to Western individuals, but a favorable durability. There is a need to reduce the high rate of premature discontinuation compared to the controlled studies.     

Effects of cigarette smoke, nicotine and cotinine on red blood cell hemolysis and their -SH capacity

BACKGROUND:

Smoking is a leading cause of premature death. Red blood cell (RBC) membrane lipids are rich in polyunsaturated fatty acids; therefore, the effect of oxygen on RBC membranes is more prominent than on other body tissues. The attachment of peroxidants to RBC membranes can result in hemolysis.

OBJECTIVES:

The present study was conducted to assess the sensitivity of RBCs to 2,2′-azo-bis-(2-amidinopropane) dihydrochloride in smokers and nonsmokers. The effect of cigarette smoke, nicotine (1 μg/mL, 1.5 μg/mL and 2.5 μg/mL) and cotinine (1.25 μg/mL, 2.5 μg/mL and 5 μg/mL) on RBC hemolysis was also examined.

RESULTS:

RBC hemolysis in smokers was 21.6% higher than in non-smokers (P<0.05). Cigarette smoke increased 2,2′-azo-bis-(2-amidino-propane) dihydrochloride-induced RBC hemolysis by 281.7%. Nicotine inhibited RBC hemolysis by 36.7% at the highest concentration used, but increased RBC hemolysis at the lower concentrations. Cotinine caused a 13.8% increase in RBC membrane peroxidation at the highest concentration used and its effects were dose-dependent. At their highest concentrations, nicotine and cotinine decreased -SH groups by 50%.

CONCLUSIONS:

The present study confirms the results from previous studies of the oxidative and destructive effects of cigarette smoke, which are detrimental to the health of both active and passive smokers.     

Edaravone suppresses postoperative reperfusion injury in rat lower extremity: An immunohistological study

PURPOSE

The present study evaluated whether the free radical scavenger edaravone (Radicut [Mitsubishi Pharma Co, Japan]) can suppress lower extremity postoperative reperfusion injury by evaluating muscle cell viability with immunohistological stain (cytochrome c oxidase stain).

METHODS

Eight Lewis male rats (460 g to 510 g) were divided into two groups. In the control group, postoperative reperfusion injury models were created by clamping the bilateral common femoral arteries for 5 h and then releasing. In the other group, 9.0 mg/kg of edaravone was administered before clamping the bilateral common femoral arteries. After 5 h of reperfusion, the bilateral triceps muscles in both groups were stained with cytochrome c oxidase stain (each n=4 × 2). The positive areas of cytochrome c oxidase stain were measured and compared, using computerized densitometry (National Institutes of Health Image program, version 1.61).

RESULTS

In the control group, the lower triceps muscles were not stained with cytochrome c oxidase. In the edaravone group, the lower triceps muscles were strongly stained with cytochrome c oxidase. The positive areas of cytochrome c oxidase stain were significantly greater in the edaravone group (133,000±12,000 μ²/mm², P<0.01) compared with the control group (8000±1300 μ²/mm²).

CONCLUSION

The present study suggests that the preoperative administration of 9.0 mg/kg of edaravone may suppress postoperative reperfusion injury in a rat model.     

Emergence of penicillin-resistant Streptococcus pneumoniae in southern Ontario, 1993�C94

Objective:

To determine the prevalence of resistance of Streptococcus pneumoniae to penicillin and other antimicrobial agents in metropolitan Toronto.

Design:

Consecutive pneumococcal isolates from different patients were obtained from two private community-based laboratories and from patients assessed in the emergency department of a tertiary-care teaching hospital in Toronto, Ontario between June and December 1993, and between March and October 1994. In vitro susceptibility testing was done by broth microdilution in accordance with National Committee for Clinical Laboratory Standards guidelines.

Results:

Twenty (7.3±3.1%) of 274 pneumococcal isolates were resistant to penicillin; six (30%) isolates had high-level resistance (minimal inhibitory concentration [mic] 2.0 μg/mL or greater); and 14 isolates had intermediate resistance (mic 0.1 to 1.0 μg/mL). Penicillin-resistant strains were also frequently resistant to tetracycline (55%), cotrimoxazole (50%), erythromycin (40%) and cefuroxime (35%). Resistant strains comprised several serotypes: 19F (six isolates), 9V (three), 23F (three), and one each of 6A, 6B, 14, and 19A; four isolates were nontypeable.

Conclusions:

There has been a recent emergence of penicillin-resistant S pneumoniae in southern Ontario. National and regional surveillance is warranted to determine the extent of the problem elsewhere in Canada.