ORIGINAL RESEARCH
Bis-[3’(5-di-tret-butyl-4-hydroxyphenyl)propyl]sulfide and dodecyl(3,5-dimethyl-4-hydroxybenzyl)sulfide are new phenolic sulfur-containing antioxidants. The purpose of this study is to develop spectrophotometric techniques for establishing the authenticity and quantification of these substances. During the validation of the procedure, calibration graphs were constructed to assess linearity at concentrations ranging from 0.001 to 0.01% for bis [3’(3,5-di-tret-butyl4-hydroxyphenyl)propyl]sulfide and from 0.0005 to 0.005% for dodecyl(3,5-dimethyl-4-hydroxybenzyl)sulfide. The correlation coefficient for bis-[3’(3,5-di-tret-butyl-4-hydroxyphenyl)propyl]sulfide was 0.999, for dodecyl(3,5-dimethyl4-hydroxybenzyl)sulfide — 0.996; the detection limit calculated using the calibration graph data was 3.14 · 10 –5 and 3.75 · 10 –5 %, the limit of quantification was 0.00103 and 0.00108% for bis-[3’(3,5-di-tret-butyl-4-hydroxyphenyl)propyl] sulfide and dodecyl(3,5-dimethyl-4-hydroxybenzyl)sulfide respectively. The value of relative standard deviation (RSD) in assessing the precision of both methods did not exceed the permissible 2%.
Thus, the developed methods can be used to establish the authenticity and for the quantification of bis-[3’(5-di-tretbutyl-4-hydroxyphenyl)propyl]sulfide and dodecyl(3,5-dimethyl-4-hydroxybenzyl)sulfide.
Aim. To determine the possibility of increasing the effectiveness of treatment of patients with chronic abacterial prostatitis due to antisclerotic enzyme therapy; to prove its positive effect on urodynamics and microcirculation in the prostate.
Materials and methods. An open, prospective, randomized, comparative study included 60 patients with category IIIa chronic abacterial prostatitis. The participants were divided into two groups: the main group (MG, 31 patients) and the comparison group (CG, 29 patients). MG patients received the baseline therapy with the inclusion of Longidaza in the form of rectal suppositories, 3000 IU of the active substance three times a week, 20 suppositories per course. CG patients received identical baseline therapy in combination with rectal suppositories containing 500 mg of methyluracil — also 3 times a week, a total of 20 suppositories per course.
The effectiveness of treatment was evaluated by the dynamics of urination and microcirculation parameters, by a decrease in scores on the National Institutes of Health — Chronic Prostatitis Symptom Index (NIH-CPSI) scale and by a decrease in the number of white blood cells in the prostatic secretion. An excellent result implied a reduction in the total score on the NIH-CPSI scale to 14 or lower, the number of leucocytes in the prostate secretion — to 10 in the field of view or less, and an improvement in urodynamics and microcirculation by 40% or more from that of initial.
Results. In MG an excellent result was achieved in 21 patients (67.7%), in CG — in 14 patients (48.3%). A good result was observed in 9 patients (29.1%) of the MG and in 11 (37.9%) of the CG. Among patients receiving Longidaza there was no effect only in one case (3.2%), and four times as many in the CG (4 patients; 13.8%).
Conclusions. Antisclerotic enzyme therapy with Longidaza in the form of rectal suppositories contributed to a significant decrease in the intensity of symptoms of prostatitis, an improvement in urodynamic parameters and prostate microcirculation.
The paper deals with the problem of providing children with safe and effective medications. The lack of medicines that ensure agerelated dosing of active ingredients and correspond to the current level of development of pediatrics is the reason for irrational (off-label, unlicensed drug) administrations. According to a survey of 157 experts from St. Petersburg (doctors of the highest category working in pediatric departments), off-label therapy is represented by 113 international nonproprietary names of drugs belonging to 40 pharmacotherapeutic groups — mainly in the form of tablets (51.79%), solutions for injection (13.86%), as well as capsules (8.64%).
The problem of children-appropriate medicines can be solved by organizing small-scale and individual pharmaceutical manufacturing of drugs. To date, on the territory of the Russian Federation, 1648 licensees have registered the right to manufacture drugs for medical use, less than 2% of licensees have the ability to manufacture narcotic drugs, psychotropic substances, 1/4 of all compounding pharmacies are concentrated in two regions of the Russian Federation: Moscow (12%) and St. Petersburg (9%). The problem of the individual manufacturing of medicines is largely due to the imperfection in regulatory environment in pharmaceutical industry. Based on the systematization of the results of fundamental interviewing of compounding pharmacies managers in St. Petersburg, ways to improving the existing mechanisms of state regulation are proposed.
An experiment, aimed at studying the influence of prophilactic administration of viburnum and eleutherococcus extracts on biochemical parameters of blood during nitrogen oxides intoxication, was performed on 80 Wistar rats. The animals were divided into 4 groups: 1st — intact, 2nd — nitrogen oxides intoxication, 3rd — viburnum extract + nitrogen oxides, 4th — eleutherococcus extract + nitrogen oxides. Nitrogen oxides intoxication was executed for 6 min at a concentration of 4.3 mg/m3 (the maximum permissible concentration in atmospheric air — 0.4 mg/m3). Intoxication was accompanied by depletion of the body’s antioxidant defense system, development of severe dyslipoproteinemia and dyslipidemia. The survival rate of animals during intoxication preceded by administration of viburnum and eleutherococcus extracts was 70%, while during intoxication without prophylactic administration of drugs — 40%.
Thus, the prophylactic intake of viburnum and eleutherococcus extracts can be recommended to residents of ecologically unfavorable regions to reduce the effects of anthropogenic impact.
In order to specify features of a structural and functional state of the heart in the combination of chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) in elderly people with arterial hypertension (AH) this research was conducted. The 15 men with COPD and BA (average age — 68.4 ± 3.6 years) were surveyed. The group of comparison consisted of 15 patients with COPD (average age — 63.4 ± 3.2 years). All patients had type B COPD.
It was revealed that in the combined broncho-obstructive pathology, unlike patients with COPD, the elderly people with AH show a greater degree of concentric hypertrophy of left ventricle with an increase in its contractility (namely, global longitudinal systolic capacity) against the background of lack of differences in its diastolic function and longitudinal in particular. When COPD and BA are combined the elderly people with AH, unlike patients with COPD, have a larger degree of impaired active relaxation of the right ventricle with an increase in its function, particularly global longitudinal systolic function, against the background of more pronounced pulmonary hypertension. The revealed features of hemodynamics of pulmonary circulation and function of right ventricle are the basis for choosing pathogenetically justified therapy aimed not only at decreasing the pulmonary artery pressure, but also at improvement of calcium mechanisms in both systole and diastole.
Introduction. Fluvoxamine is used for treatment of patients with depressive disorders comorbid with alcohol use disorder while a considerable part of this group does not properly respond to therapy, the development of dose-dependent adverse drug effects is noted in many patients. In early studies it was shown that CYP3A is involved in biotransformation of fluvoxamine the activity of which depends in large part on the encoding gene polymorphism.
Aim of the Research. To study CYP3A activity influence on the efficacy and safety profile of fluvoxamine in patients with comorbid depressive disorders and alcohol addiction.
Materials and Methods. 96 males with depressive disorders comorbid with alcohol use disorder took part in the study (average age — 39.9 ± 15.4 years). Fluvoxamine at a dose of 125.0 ± 50.3 mg a day was used for treatment. The efficacy profile was estimated by means of the validated psychometric scales, and the therapy safety profile — by means of the UKU side effects rating scale. Genetic typing was performed by the method of real time PCR . CYP3A activity was estimated by high performance liquid chromatography based on the ratio of endogenous substrate and its metabolite concentrations in urine (6β-hydroxycortisol/cortisol).
Results and Discussion. In the course of the analysis no statistically significant results were obtained in terms of the effectiveness assessment (scores on the HAMD scale by the end of therapy: genotype GG — 4.0 scores [2.0; 8.0], genotype GA — 3.0 scores [1.0; 5.0], p > 0.999) and safety assessment (scores on the UKU scale: genotype GG — 3.0 scores [1.0; 5.0], genotype GA — 4.0 scores [3.0; 4.0], p > 0.999).
Conclusion. In a study conducted in a group of 96 patients with depressive disorders comorbid with alcohol addiction the absence of influence of CYP3A activity on the parameters of clinical efficacy and safety of fluvoxamine was demonstrated.
To determine the efficacy and safety of the drug based on immobilized subtilisin (SUBT), we conducted experimental (using Wistar and Balb/C male rats) and clinical (VETTER-1 — Venous Thrombosis Therapy) studies. Experimental studies have shown the direct thrombolytic effect of SUBT on 1-, 2- and 24-hour blood clots (in vitro) and the absence of local changes in rats with κ-carrageenan-induced thrombosis (in vivo). In a clinical study, patients receiving SUBT showed an increase in blood flow by 5% from the initial, or recanalization of a vein which was observed 1.5–1.6 times more often than in patients receiving placebo.
Thus, a drug based on SUBT can be used in the treatment of venous thrombosis.
The pharmacological activity of vaginal suppositories with the garden sage leaves solid extract (GSLSE) was studied on a model of the induced vaginitis during experiment which was conducted on 36 female rats. Animals were divided into 6 groups (6 rats in each one): the 1st group was control one (intact rats); the 2nd group was with the induced vaginitis; the 3rd group was with the induced vaginitis and pharmacological correction by vaginal suppositories Metronidazole in a dose of 43 mg/kg; the 4th group was with induced vaginitis and sea-buckthorn oil suppositories in a dose of 43 mg/kg; the 5th group was the induced vaginitis and vaginal suppositories with GSLSE in a dose of 4.3 mg/kg; the 6th group was the induced vaginitis and vaginal suppositories with GSLSE in a dose of 8.5 mg/kg. An experimental vaginitis was modeled by single intravaginal injection of phlogogen at a dose of 0.2 ml per one animal.
It is established that the studied drug in a dose of 4.3 mg/kg shows the maximum regenerative activity. So, when correcting vaginitis with the studied drug in a dose of 4.3 mg/kg thickness of epithelium was 65.06 [38.2–89.4] μm (when treated with Metronidazole suppositories and suppositories with sea-buckthorn oil 43.3 [34.7–55.6] and 76.6 [48.7–107.1] μm respectively), and the ratio of epithelium and stroma of lamina propria of vaginal mucosa was close to normal.
Thus, vaginal suppositories with GSLSE are perspective for further studying as a potential tool for the treatment of infectious and inflammatory diseases of lower female genital tract.