Ewa Jaźwińska−Tarnawska

OBJECTIVE: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its metabolism is genetically controlled by a cytochrome P450 isoenzyme named CYP2D6, which shows polymorphism in human population. The aim of this paper was to determine the correlation between the antiarrhythmic efficacy of PPF and the oxidation phenotype. SUBJECTS AND MATERIAL: The study group consisted of 42 patients, aged 36 to 75 years, suffering from paroxysmal atrial fibrillation (AF). The oxidation phenotype was described by the metabolic ratio (MR) of sparteine. The MR value separated the group of poor metabolizers (MR > 20) from the group of extensive metabolizers (MR < 20) with the subgroup of very extensive metabolizers (MR < 1). METHOD: The study was conducted during a 3-month PPF therapy for the prophylaxis of paroxysmal atrial fibrillation. PPF was given orally, 300-450 mg/day. The oxidation phenotype was checked prior to the administration of PPF. Serum concentration of PPF at 7, 11 days and the end of PPF therapy were determined. Statistical analysis of data was performed with the chi2 test and the Pearson's correlation methods. RESULTS: In the group of 42 patients, PPF therapy was 100% effective in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy was observed with efficacy 0% in very extensive metabolizers (VEM). The correlation between oxidation phenotype and the ability to maintain sinus rhythm (SR) was statistically significant (r = 0.414, p < 0.05). CONCLUSIONS: The antiarrhythmic efficacy of propafenone depends on the oxidation phenotype; 100% efficacy occurred in the group of poor metabolizers whereas PPF, at the dose tested, was ineffective in very extensive metabolizers.

The possibility of applying liposomes as a topical drug delivery system is still a matter of intensive research. The purpose of this study was to determine the suitability of liposomes as carriers of naproxen and to prove their impact on the effectiveness of transdermal permeation of an active substance. The study was conducted with the use of Franz Diffusion Cell System by comparing the efficacy of a preparation containing 20% of phosphatidylcholine (PC) and 10% of naproxen with reference preparations, i.e., a formulation containing 10% of naproxen without PC and the commercial product Naproxen 10%, gel. The largest transdermal penetration flux of naproxen and the highest efficacy of naproxen permeation were obtained for the formulation containing 10% of naproxen and 20% of PC. The study of the influence of liposomes size and topology on the transdermal diffusion of naproxen (large unilamellar vesicle, LUV, multilamellar vesicle, MLV) showed that there was no statistically significant difference in the flux or total amounts of transdermally diffused naproxen between compared formulations. In conclusion, liposomes present in a formulation double the efficacy of the transdermal permeation of naproxen in vitro compared to reference preparations containing no carriers. Better permeation effect of a formulation was not related to the liposome type (LUV or MLV).

BACKGROUND: [corrected] Osteomyelitis and arthritis still present a serious diagnostic and therapeutic problem. Difficulties arise in particular in the treatment of acute hematogenic osteomyelitis (AHO) in newborns where mega-doses of gentamicin are administered locally for about 3 weeks. Gentamicin possesses strong oto- and nephrotoxicity and the occurrence of these adverse effects depends on the duration of treatment and the serum drug concentration. OBJECTIVE: Aim of the study was to evaluate the influence of local gentamicin application on auditory and kidney functions. MATERIAL AND METHODS: Twenty newborns (14 boys and 6 girls) with AHO were treated at the Department of Pediatric Surgery, Marciniak Hospital, Wroclaw, Poland, by local implantation of miniseptopal or gentamicin sponge. Serum urea, creatinine, antibiotic concentrations and NAG activity/g creatinine ratio in urine were estimated before and 1, 4, 8, 16 days after the operation and compared to values in the control group. Brainstem-evoked auditory potentials (BAEP) were examined before, during the first 3 weeks, and 6-11 months after gentamicin implantation. RESULTS: Mean gentamicin serum concentrations were: 0.67 +/- 0.98 mg/l on the 1st day, 0.16 +/- 0.37 mg/l on the 4th day, 0.03 +/- 0.09 mg/l on the 8th day, 0.01 +/- 0.03 mg/l on the 16th day after operation and did not exceed the upper limit of the therapeutic range. N-acetyl-beta-D-glucosaminidase (NAG)/g creatinine in urine ratios were satisfactory: 77.91 +/- 36.22 UI/g before the operation, 146.51 +/- 82.27 UI/g on the 4th, 162 +/- 111 UI/g on the 8th, 168 +/- 59.83 UI/g on the 16th day after operation and were statistically significantly (p < 0.05) higher than values in the control group. Serum urea and creatinine levels were in the normal range in all groups. Initial BAEP were well in the normal range in 15 of 16 children before treatment and in 14 of 16 children after treatment. CONCLUSIONS: Locally applied gentamicin as miniseptopal or sponge in newborns produces gentamicin concentrations close to the minimal therapeutic serum concentration which are present over a prolonged period. The raised NAG values in urine and normal serum urea and creatinine levels during treatment with gentamicin without concomitant clinical symptoms of renal failure suggest subclinical destruction of the renal tubules. Lack of change in BAEPs shows that there is no impairment of auditory function.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn's disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.