High virologic sustained response for former young intravenous drug users with chronic hepatitis C treated by pegylated interferon-alpha plus ribavirin.

AIMS: The aim of this clinical study was to assess virological response at end-of -treatment (ETR), sustained virological (SVR) and biochemical response in former drug users with chronic hepatitis C treated with PEG-IFN-alpha and R. PATIENTS: Ninety two former drug users (21 F, 71 M) average age 27 years (18 to 41 years) and previously not treated with IFN-alpha and R (naive patients, pts) were evaluated for their virological and biochemical response. Standard treatment regimen of either 24 or 48 weeks was applied in patients with genotype 3 or genotype 1, respectively. SVR was considered if viral tests (HCV RNA) were negative 24 weeks after the end of treatment. RESULTS: Overall SVR was attained in 87 (95%) of 92 treated patients, and therapy failed in 5 pts with genotype 1. In genotype 1 patients ETR and SVR were 81% and 86%, respectively (p < 0.001). In genotype 3 patients ETR and SVR were 98% and 100%, respectively (p < 0.001). ALT levels decreased significantly after 12 weeks of therapy (ALT 1.61 vs 0.64 micro/kat/l, p < 0.001) and were at normal levels during follow-up. CONCLUSIONS: Crucial predictive factors resulting in high SVR were the younger age in combination with low stage of liver fibrosis, relatively short duration of viral infection, high proportion of genotype 3 and excellent adherence of patients to treatment regimen than previously not treated with IFN-alpha and R (naive patients). High proportion of SVR in former drug users has been achieved in patients with genotype 3 (100%) and genotype 1 (86%). The most decisive prognostic factor which favors high therapeutic efficacy appears to be young age and early onset of anti-HCV treatment (Tab. 3, Fig. 1, Ref. 33). Full Text (Free, PDF) www.bmj.sk.

Dilemmas regarding the proper route of adrenaline administration in anaphylaxis.

The authors outline current practice regarding the pre-hospital use of adrenaline. They conclude that intramuscular adrenaline recommended in the current European guidelines may not be the only correct route of administration. Both intradermal and intravenous routes may be more appropriate in certain situations. The decision as to which route is the most appropriate in a particular situation will depend on several factors discussed in the article. Nevertheless, the early use of intramuscular adrenaline, particularly in pre-hospital or in the unmonitored setting, still warrants direct comparison with intravenous adrenaline to examine their relative efficacies compared with complication rates. Similarly, the benefits and risks of subcutaneous adrenaline in patients with milder reactions or increased cardiovascular risk warrant further investigation (Tab. 3, Ref. 24).

[Biological properties of coenzyme Q10 and its effects on immunity]. / Biologické vlastnosti koenzýmu Q10 a jeho vplyv na imunitu.

Coenzyme Q10, a vitamin-like substance, represents a components of the complex antioxidant system of the human organism. The paper presents its structure, physiological function and the role in the disease pathogenesis with the accent on the supplementation therapy during human immune system disturbances, including infectious and oncological diseases.

Antiasthmatic effects of nedocromil sodium.

Accumulating data indicate that bronchial asthma is a chronic inflammatory disease. Airway inflammation and it's control became a principal focus in asthma treatment. Nedocromil sodium is chemically nonsteroidal anti-inflammatory agent for the treatment of mild to moderate asthma. The aim of the study was to determine the effects of NS on bronchial hyperresponsivness and eosinophil activation markers isolated from peripheral blood of asthmatics with mild intermittent asthma. Twenty nine patients of both sexes (17 women, 12 men) with average age of 34 years were recruited into the clinical open study. Bronchial responsivness was assessed by metacholine challenge test prior to starting therapy with NS (preparation Tilade mint aer) and 3rd week and 9th week of follow up. Baseline lung function tests were performed at intervals before treatment and at 3rd and 9th week, respectively. Eosinophil activation markers were determined before and after 3rd and 6th week. Assessement was done by flow cytometry using standard monoclonal antibodies. Bronchial responsivness decreased significantly at 3rd and 9th week of follow up (provocation dose--PD20 increased significantly, p < 0.05, p < 0.02, respectively). Improvements of baseline lung function tests were observed in majority of parameters: FVC (p < 0.01), FEV1 (p < 0.01), FEV1/FVC (p < 0.01), MEF 25 (p < 0.03), MEF 50 (p < 0.01), MEF 25-75 (p < 0.01), PEF (p < 0.01) after 3rd week, however the enhancement of improvement was seen in majority of parameters after 9th week of the study. Significant reduction of eosinophil activation markers expression was noticed: CD69 (p < 0.05, p < 0.01) and HLA DR (p < 0.05, p < 0.05) after 3rd and 6th week, respectively and CD66 (p < 0.05) after 3rd week and CD81 (p < 0.05) after 6th week of follow up. NS possessed complex antiasthmatic effects resulting in decrease of bronchial responsivness and reduction of eosinophil activation markers in mild asthmatics. The tolerance of the drug was good and no adverse effects have been reported. NS is effective prophylactic drug recommended for use in both adults and children in long-term management of mild asthma. (Tab. 2, Fig. 1, Ref. 27).

Decreased levels of coenzyme Q(10) in patients with bronchial asthma.

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive therapy in complex management of disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, and beta-carotene both in plasma and whole blood, and malondialdehyde (MDA) and eosinophil cationic protein (ECP) in plasma of asthmatics (As). METHODS: Fifty-six As (15 males and 41 females) aged from 19 to 72 years (mean age 46 years) suffering from allergic asthma were enrolled into the study. The control group comprised 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: The concentrations of CoQ10 decreased significantly both in plasma and whole blood, compared with healthy volunteers (0.34 +/- 0.15 micromol/l vs. 0.52 +/- 0.15 micromol/l, 0.33 +/- 0.14 micromol/l vs. 0.50 +/- 0.13 micromol/l, P < 0.001, P< 0.001, respectively). The levels of alpha-tocopherol were decreased both in plasma and whole blood in comparison with controls [24.10 micromol/l (19.8; 30.5), vs. 33.20 micromol/l (28.25; 38.05), 17.22 +/- 6.45 micromol/l vs. 21.58 +/- 7.92 micromol/l, P= 0.006, P = 0.01, respectively]. The levels of MDA were elevated over the reference range in both groups (reference range < 4.5 micromol/l). No changes were seen in beta-carotene concentrations. Positive correlation was found between whole blood CoQ10 and alpha-tocopherol concentrations. CONCLUSION: Results of the study suggest a possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide a rationale for its supplementation.

Efficacy and tolerability of piroxicam-beta-cyclodextrin in the outpatient management of chronic back pain.

BACKGROUND: Piroxicam-beta-cyclodextrin (PBC) is the first nonsteroidal anti-inflammatory drug (NSAID), in which the active substance is complexed with the cyclic oligosaccharide cyclodextrin, which acts as an artificial receptor. This complex allows single molecules of the NSAID to be released adjacent to the gastrointestinal mucosa, instead of crystals. Since the piroxicam is immediately bioavailable in this formulation, the onset of action is similar to that of a parenteral drug. Since the time contact with gastric mucosa is reduced, the risk of direct-contact gastric irritation is also reduced. There is good evidence that PBC is beneficial in managing acute non-specific back pain (BP) but sufficient evidence on chronic BP is lacking. METHODS: Thirty-one eligible patients aged 18-85 years, resistant to previous therapy with different NSAIDs, were treated with PBC 20 mg once daily in a 40-day open-label noncomparative study. The patients experienced chronic BP defined as pain between the occipital region and gluteal fold, lasting for at least 6 weeks but not more than 6 months. Efficacy was assessed by changes in pain intensity, paravertebral tonus, functional impairment and morning stiffness using a 4-point numerical rating scale. Patients also self-assessed nocturnal and diurnal pain using the visual analogue scale. Tolerability was assessed by adverse events and routine laboratory evaluations. Global assessment of efficacy and tolerability by physician and patients was performed at the last visit. RESULTS: Using intention-to-treat analysis, all efficacy assessments demonstrated statistically significant improvements over baseline at each follow-up. 90.3% of the patients evaluated the efficacy of PBC as improved or greatly improved, and investigators rated the treatment as improved or greatly improved in 87.1% of patients. Remission was achieved in 19.3% of the patients. Tolerability was also rated highly, with 83.9% of the patients characterizing PBC treatment as good or very good, and the investigators rated the treatment as good or excellent in 87.1% of the patients. Drug related adverse events were reported in 9.7% of patients and prompted discontinuation of the study medication in 3.2% of patients. No serious adverse events were reported. CONCLUSION: These results suggest that the newly developed dosage form of piroxicam is effective and well tolerated in the treatment of patients with chronic BP. Thus, PBC, may be an important new treatment option in this condition. (Tab. 3, Fig. 3, Ref. 36.).

Levels of coenzyme Q10 in asthmatics.

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive approach in complex management of the disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, beta-carotene and malondialdehyde (end-stage parameter of lipid peroxidation) in asthmatics (As). METHODS: Fifty six As (15 males and 41 females) aged from 19 to 72 yrs (mean age 46 yrs) were enrolled into the study. The control group comprised of 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: Concentrations of CoQ10 and alpha-tocopherol, decresed significantly both in plasma and whole blood, compared with healthy volunteers (p < 0.009, p < 0.004; p < 0.035, p < 0.001, respectively). The level of MDA was elevated, but not statisticaly significantly. No changes were seen in beta-carotene levels. Positive correlation was found between concentrations of CoQ10 and alpha-tocopherol. CONCLUSION: Our results suggest possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide rationale for its supplementation with clinical evaluation. (Tab. 2, Fig. 1, Ref. 39.).