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BACKGROUND: Congenital hyperinsulinism (CHI) is a rare life-threatening disease characterised by persistent hypoglycaemia as a result of inappropriate insulin secretion, which can lead to irreversible neurological defects in infants.AIM: To evaluate neurophysiological characteristics of central nervous system in children with congenital hyperinsulinism treated according to the international protocol in Russian Federation.MATERIALS AND METHODS: Our retrospective, prospective cohort study included 73 patients who received treatment for CHI according to the current international protocol at different departments of the Almazov National Medical Research Centre from 2017 to 2022. All patients underwent a comprehensive examination, including electroencephalography (EEG).RESULTS: Among 73 patients with CHI, 35% (23) had focal form of the disease, 65% had non-focal form (49% (39) — diffuse form, 16% (11) — atypical form). All patients with focal form of CHI had a recovery as an outcome.Analysing the EEG data we found that paroxysmal activity was recorded in 23 patients (32%), 50 patients did not have paroxysmal activity (68%). Diffuse changes were observed in 47 patients (64%), whereas 26 patients (36%) were absent of it. By constructing Kaplan-Meier curves we found that the alpha rhythm is formed significantly (p=0.026) earlier in patients with a focal form of CHI.CONCLUSION: CHI patients treated according to the international guidelines in Russian Federation show rather positive neurological outcome. We established that alpha rhythm earliest formation is associated with focal form of CHI.

Introduction. Diabetes mellitus type 1 (T1DM) in children and adolescents occupies a leading place in the structure of chronic diseases of childhood. Despite modern advances in the treatment and control of CT 1, adolescents have problems with glycemic control in comparison with other age groups.Aim. Is to estimate the correlation between the degree of compensation for diabetes in adolescents and the features of the personality profile, emotional and behavioural characteristics and environmental factors.Materials and methods. The study included 101 children aged 11 to 17 years, treated to pump insulin therapy or multiple injections of insulin. Adherence and compliance to therapy was assessed using the Medication Adherence Questionnaire (MAQ) and the Self Care Inventory-Revised Version (SCI-R). Emotional and behavioral problems were evaluated using the Youth self-report for ages 11-18. Characterization of personality profile was assessed using the The Sixteen Personality Factor Questionnaire». Results. Diabetes was compensated in 25% of children (HbA1c < 7,0%). A statistically significant relationship was established between the degree of patient compliance and the level of HbA1c. The predictive role of individual psychological characteristics on compliance has been determined. Factors such as realism and acceptance of moral norms have a positive impact on compliance.Conclusions. The therapy compliance indicator is the most significant indicator of better compensation for type 1 diabetes in adolescents. The personality traits of adolescents, such as acceptance of moral norms and realism — sensitivity have a predictive effect on the therapy compliance.

Backgraund: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders found during pregnancy. Currently, it is relevant not only to search optimal target levels of glycemia during pregnancy, but also to study the ­effect of different glycemia levels on fetal development and further changes in glucose and lipid metabolism in children.Aims: To describe perinatal period, physical development and metabolic status of children born to women with GDM and different glucose levels during pregnancy.Materials and methods: The perinatal period features and anthropometric parameters at birth were evaluated in 300 children born to women with GDM and different levels of glycemia during pregnancy. Over the course two years, 141 children have been evaluated for physical development parameters and glucose and lipid metabolism. Fasting and postprandial glycemia was measured with glucometer for 14 days in 33 children aged 1 to 4 years.Results: The anthropometric parameters of children at birth did not differ from the parameters of the control group (p> 0.05) when during pregnancy fasting blood glucose was less than 5.1 mmol / l and 7.0 mmol / l 1 hour after a meal. The glycemia in women above this level was associated with an increase of frequency and risk of a body mass index, body mass / length ratio and head circumference “above average” in children at birth (p 0.05). The change in metabolic parameters was represented by neonatal hypoglycemia in children of GDM group (GDM group — 23%, control group — 3.5%, p = 0.000002), the least risk of which occurred in group with the lowest fasting and postprandial glycemic values during pregnancy. Fasting glucose, and insulin levels, НOMA index, triglycerides and cholesterol, as well as monitoring fasting and postprandial glycemia for 14 days, were obtained no significant differences between the comparison groups of children (p> 0.05).Conclusions: The lowest risks of neonatal hypoglycemia and anthropometric deviations at birth were associated with the lowest glycemia levels during pregnancy, which correspond to the criteria of the Russian clinical guidelines.

A series of 4-alkyl-5-bromo-2,4-dihydro-2-(thietan-3-yl)-1,2,4-triazol-3-ones (IIa-g) were synthesized by reacting 5-bromo-2,4-dihydro-2-(thietan-3-yl)-1,2,4-triazol-3-one (I) with alkyl halides and dimethyl sulfate. The structures of the synthesized compounds were confirmed by IR, PMR, and 13C NMR spectroscopic data. The antidepressant activity of the synthesized compounds in non-inbred male mice was investigated using tail-suspension and forced-swim tests. Compounds I and IIa,c,f,g after a single intraperitoneal injection produced antidepressant effects in screening tests and did not cause sedative and/or psychostimulatory effects in the open-field test. Compound I produced an antidepressant effect comparable to that of fluoxetine, had low toxicity (class IV toxicity), and was superior to fluoxetine in therapeutic index and strength of the antidepressant effect after a course of administration. The calculated physicochemical properties and toxic risks showed that all synthesized compounds complied fully with Lipinski’s rule of five. The calculated drug score and absence of predicted toxic risks for the most active compound I suggested that it was promising for creating a new pharmaceutical substance with antidepressant activity.

Ethyl 2-[8-Arylmethylidenehydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetates (IV) were synthesized via reactions of ethyl 2-[8-hydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetic acid (III) with various benzaldehydes and acetophenones. The structures of the compounds were elucidated using IR and NMR spectroscopy and elemental analysis. The antiplatelet, anticoagulation, antioxidant, and anti-inflammatory activities were assessed in vitro and in laboratory animals to identify promising compounds exhibiting antiplatelet (hydrazone IVd) and antioxidant properties (hydrazone IVb). Both IVb and IVd according to in silico calculations were characterized by the absence of toxic risks (mutagenicity, oncogenicity, reproductive toxicity, local irritation) and had acceptable topological polar surface area so that they were promising.

This study presents literature data over the past few years on markers of acute myocardial damage after radiofrequency ablation. Information on markers such as troponin I and T, creatine phosphokinase and its fractions, CRP and interleukins and myoglobin is presented in detail. For each potential myocardial damage indicator, data related to their expression site, chemical basis of each marker and correlation between the degree of damage caused by radiofrequency exposure and the levels of various biomarkers of myocardial damage are provided.Received 12 November 2019. Revised 26 February 2020. Accepted 27 February 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and study design: O.L. Zajfrid, R.B. Tatarsky, E.S. VasichkinaDrafting the article: O.L. Zajfrid, K.A. Chueva, A.V. Mikhailov Critical revision of the article: O.L. Zajfrid, R.B. Tatarsky, E.S. Vasichkina, I.L. Nikitina, D.S. LebedevFinal approval of the version to be published: O.L. Zajfrid, K.A. Chueva, E.S. Vasichkina, A.V. Mikhailov, D.S. Lebedev, I.L. Nikitina, R.B. Tatarsky

A series of 3-alkyloxy(sulfanyl)thietane-1,1-dioxides were synthesized by reacting 3,5-dibromo-1-(1,1-dioxothietanyl- 3)-1,2,4-triazole with sodium alkoxides and thioalkoxides. Compounds IIa (2 mg/kg) and IIh (6 mg/kg) exhibited antidepressant-like effects at doses equimolar to amitriptyline (10 mg/kg); IId (2 mg/kg) and IIb (2 and 5.7 mg/kg), effects associated presumably with anxiolytic properties. Prediction of toxic risks, drug-likeness, and physicochemical properties of the molecules using the Osiris DataWarrior and Property Explorer programs showed that the compounds should not have adverse effects on reproductive functions and should not possess oncogenic, mutagenic, and irritant properties.

A series of 8-amino-substituted 1-butyl-3-methylxanthines containing a thietane ring were obtained in 47 – 96% yields by reacting 7-(thietanyl-3)-, 7-(1-oxothietanyl-3)-, and 7-(1,1-dioxothietanyl-3)-8-bromo-1-butyl-3-methylxanthines with piperidine and morpholine. Reaction of 8-amino-substituted 1-butyl-3-methyl-7-(1,1-dioxothietanyl-3)xanthines with sodium ethoxide synthesized 8-amino-substituted 1-butyl-3-methylxanthines in 85 – 98% yields. The structures of the compounds were confirmed by IR and PMR spectroscopy. The synthesized compounds exhibited antidepressant activity.

BACKGROUND: Self-monitoring of blood glucose (SMBG) with glucometers provides only a snapshot of the glycemic profile and is accompanied by significant psychological discomfort and pain, especially in children. Flash Glucose Monitoring System — FreeStyle Libre (FSL) overcomes many of the barriers associated with glucose measurement and improves metabolic control.AIM: To evaluate the efficacy of FSL in children with type 1 diabetes mellitus (T1DM) in terms of glycemic control, episodes of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA).MATERIALS AND METHODS. A multicenter, prospective, observational study in real clinical practice was carried out. A total of 469 subjects (258 boys and 211 girls) aged 4–18 were included in the study. The median age was 11.3 (8.4–14.6) years, duration of T1DM — 4.2 (2.1–7.1) years. After FSL start, patient was followed up for 6 months.RESULTS: After 3 and 6 months of FSL use, HbA1c significantly decreased from 7.4% to 7.1% and 7.2%, respectively (pCONCLUSION: The Study demonstrated a significant improvement in metabolic control in children with T1DM 6 months after FSL start: decrease in HbA1c, accompanied by reduction in incidence of DKA and SH.

Tadalafil is a drug from the phosphodiesterase-5 inhibitors (PDE-5) group, which is used to treat erectile dysfunction (ED), lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) and ED with LUTS in patients with BPH. The efficacy and safety of tadalafil were reviewed. The focus was on cardiovascular safety of tadalafil due to frequent cardiovascular comorbidities in patients with ED. We concluded that tadalafil is well tolerated and safe in patients with cardiovascular comorbidities and, in addition, has a beneficial effect on the cardiovascular system.

In order to assess the growth and development of schoolchildren living in a metropolis, 809 boys aged 12 to 15 years were examined in St. Petersburg. Characteristics of indicators of physical development are given according to the norms of «WHO Growth Reference 2007»; the level of puberty - with the help of a phenotypic evaluation according to the method of M.V. Maksimova. The high prevalence of overweight (13.3%) and obesity (12.5%) among schoolchildren was revealed. It is noted that the initiation of the boys’ puberty occurs at the earlier time compared with the data given in the literature.

The physical development indicators in the context of the social and hygienic researches are important health parameters of the children’s population and indices of the social well-being of the society. With the purpose to define the modern trends of the children physical development using the random sampling technique, 6,207 school children (3,225 boys and 2,982 girls) aged from 7 to 17 years were examined in the various districts of Saint-Petersburg. The somatometry (body height, weight and ribcage circle) was carried out and the arithmetic mean values (M), and error in means (m) were calculated. The data analysis has shown that in all age groups, except for 11–12-year-old children, the indicators of the body height are higher for the boysthan those for the girls. The pubertal growth acceleration of the body height in girls becomes perceptible during the period from 9 to 13 years of age; in boys, it starts after 11 years and it is prolonged up to 15 years of age. The girls’ body weight is lower in all groupsthan that in the boys; only at the age from 11 to 13 years, the body weight is practically equal to the indicators of the boys of the same age. The ribcage circle indicators are also higher in boys than in girls in all age groups. The analysis of the annual somatometric indicator increase has revealed the considerable decrease in the value of gain in the body height in both the boys and girls on the 11th year of life as well as the body weights in boys that demands the additional analysis of cause factors. The revealed trends of the physical development of schoolchildren in the conditions of the megalopolis demand the in-depth analysis of the factors defining these tendencies with the subsequent development and carrying out of the preventive measures.

Introduction Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases and various neuromuscular disorders. Often RCMP occurs with severe symptoms of heart failure and has an poor prognosis. Given the presence of structural myocardial abnormalities, atrial dilatation, this group of patients has a high risk of heart rhythm and conduction disturbances. Objective To present our clinical experience in RCMP with the heart rhythm and conduction disturbances in children. Material and methods The study was approved by the Institute Ethical Review Board. On behalf of the children enrolled in the study, written informed consent was obtained from the next of kin. The study included 18 children with RCMP presented with heart failure class II-IV. The genotyping was performed to all patients. The identified genetic variants were classified according to ACMG guidelines. We analyzed clinical history, data of physical examination, laboratory findings, ECG, echocardiography, Holter monitoring, genetic test, cardiac MRI and CT performed according to clinical indications and physician's. Results Mean age of RCMP manifestation was 2,1 y.o. [0–11] with HF as a main clinical feature. Rhythm and conduction disorders were reported in 83% (n=15) of children. The structure of the disorders included: atriventricular block 1–2 degrees in 22% (n=4), supraventricular disorders (extrasystole, tachycardia, atrial fibrillation) in 44% (n=8), ventricular disorders (extrasystole, tachycardia) in 16% of patients (n=3). One patient had a combined rhythm and conduction disorder (sinus sick syndrome, atrial fibrillation, supraventricular and ventricular tachycardia), which required implantation of a pacemaker with a defibrillator function. In one patient, the manifestation of the disease was with hemodynamically significant permanent-recurrent atrial tachycardia. Mortality in this group of patients was 27% (= 5), the cause of death was the progression of heart failure in 3 children and sudden arrhythmial death in 2 patients. Conclusions Thus, RCMP is a severe, genetically caused, with early manifestation progressive disease with high risks of rhythm and conduction disturbances, sudden arrhythmial death. According to the testimony, patients should receive antiarrhythmic therapy and, if necessary, pacemaker implantation is indicated.

Tadalafil is a drug from the phosphodiesterase-5 inhibitors (PDE-5) group, which is used to treat erectile dysfunction (ED), lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) and ED with LUTS in patients with BPH. The efficacy and safety of tadalafil were reviewed. The focus was on cardiovascular safety of tadalafil due to frequent cardiovascular comorbidities in patients with ED. We concluded that tadalafil is well tolerated and safe in patients with cardiovascular comorbidities and, in addition, has a beneficial effect on the cardiovascular system.

3-Aryloxy- and 3-phenylsulfanylthietane-1,1-dioxides were synthesized by reacting 3,5-dibromo-1-(1,1-dioxothietan-3-yl)-1,2,4-triazole with sodium phenolates and thiophenolate. The 5-aryloxy- and 5-arenesulfonyl-3-bromo-1-(1,1-dioxothietan-3-yl)-1,2,4-triazoles were synthesized via oxidation by H2O2 of 5-aryloxy- and 5-phenylsulfanyl-3-bromo-1,2,4-triazoles containing thietane or thietane oxide rings. The 3-substituted thietane-1,1-dioxide IId (2 and 20 mg/kg) displayed antidepressant properties in tail-suspension (TST) and forced-swim tests (FST) that were comparable with those of imipramine. Low toxicity risks (mutagenicity, tumorigenicity, irritation, reproductive toxicity) and satisfactory pharmacokinetic characteristics (correspondence to Lipinski’s rule of five) were predicted (Osiris Property Explorer, Molinspiration) for it.

2-[3-Methyl-7-(thietanyl-3)-1-ethylxanthinyl-8-thio]acetic acid hydrazide was synthesized in two steps by our improved method. The structures of the synthesized compounds were confirmed by IR and NMR spectroscopic data. The acute toxicity was studied. The LD50 values were 700 mg/kg for outbred albino mice. Tail-suspension tests (TST) and forced swimming tests (FST) found that 2-[3-methyl-7-(thietanyl-3)-1-ethylxanthinyl-8-thio]acetic acid hydrazide exhibited antidepressant activity that was most pronounced at a dose of 12 mg/kg.

Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as key gatekeepers of the gonadotropic axis. Unlike its role at the hypothalamus on GnRH secretion, the effects of kisspeptins on gonadal and other peripheral tissues need to be clarified.To investigate the impact of experimentally induced hypogonadism in male rats on kisspeptins signaling in androgen-dependent tissues and blood.Wistar male rats (total number 31) were used. Rats were divided into four groups. Group 1 (control, prepubertal rats aged 2 months, n = 7). Group 2 (control, pubertal rats aged 4 months, n = 6). Group 3 (unilaterally gonadectomized (ULG) in neonatal period). Group 4 (ULG testosterone-treated with testosterone (T) propionate 5 mg/kg/d during 10 days). In all the four groups density of GPR54 in testes and muscle and serum kisspeptin levels and T levels were estimated. The data was expressed as median values (Me) that were compared by Wilkokson criterion.Density of GPR54 in gonads in group 3 was lower than in group 2 (Me 0,88 ng/mg vs 1,13 ng/mg, p0,05) and similar to group 1(Me 0,92 ng/mg). Unlike above, density of GPR54 in muscle in all groups 1,2,3 was not any differences (Me 0,1; 0,12; 0,13 ng/mg, p0,05).Generally, density of GPR54 in group 2 in gonads was significantly higher than in the same group in muscle (Me 0,784 ng/mg vs 0.114 ng/mg, p0,01). In the group 3 a significant decrease in serum levels of T (Me 15,39 ng/mg) in comparison with group 2 (Me 20,02 ng/mg, p0,01) was invented. However, serum levels of kisspeptins in both groups had not any differences (0,27 ng/mg and 0,26 ng/mg, p0,05). Treatment with testosterone propionate of the rats of group 4 lead to increase of serum level of T (from 15,39 ng/mg to 26,26 ng/mg, p0,01), but didn`t modify the density of GPR54 in gonads (Me 0,79 ng/mg).Hypogonadism lead to decrease of kisspeptins signaling in peripheral androgen-dependent tissues. Serum level of kisspeptins is physiologically low and, probably, it can not be used as a marker of activity of kisspeptins system. Efficacy of treatment with testosterone is not enough that is required a novel therapeutic resources.

The patients with obesity are known to suffer 25-hydroxy vitamin D (25(OH)D) deficiency, but the relationship between these two conditions remains unclear. The blood 25(ON)D levels in practically healthy women were compared with the amount and distribution patterns of the fatty tissue and with the content of plasma adipocytokines. The absence or deficit of vitamin D was documented in 61.3% of the women included in the present study. They exhibited negative correlation between 25(ON) D levels and body weight. The patients with obesity were characterized by correlation between the 25(ON)D levels and waist circumference, body weight, BMI, and the amount of fatty tissue. The women of reproductive age with the reduced blood 25(ON)D level ( OR 1.86 [0.88—3.95]; CI 95%) or 25(ON)D deficiency (OR 2.23 [1.03—4.80]; CI 95%) were at a higher risk of development of obesity compared with the women in whom the 25(ON)D levels were in excess of 75 nmol/l. The study confirmed correlations between adypocytokine levels and the amount of fatty tissue even though it failed to demonstrate a significant relationship between the levels of adipocytokines and vitamin D.

Characteristic structural signatures of antidepressant agents were determined using the SARD-21 computer-aided modeling system. The influence of these signatures on the antidepressant activity was evaluated. This information was used to develop a mathematical model capable of predicting the antidepressant effectiveness of 1,2,4-triazoles and thietane-1,1-dioxides at a recognition level of 80%. The established structural parameters can be used to design new highly effective antidepressants and to predict a priori antidepressant activity in the 1,2,4-triazole and thietane-1,1-dioxide series.

Aim. To study the effect of new derivatives of 3 substituted tietan-1,1-dioxide on some mediator systems of the brain in order to determine the possible mechanism of antidepressant effect of these compounds. Methods. In an experiment with male mice studied was the effect of three most active derivatives of tietan-1,1-dioxide, which exhibit antidepressant properties [3 methooxytietan-1,1-dioxide (H14), 3-(2-isopropoxy-5-methylphenoxy)-tietan-1,1-dioxide (H40) and 3-phenylsulphonyltietan-1,1-dioxide (N69)] on the neurotransmitter systems of the brain. In the experiments used were the tests of pharmacological interaction with a sympatholytic reserpine, with a nonselective agonist of dopamine receptors apomorphine, with a dopamine receptor antagonist haloperidol, with a precursor of serotonin 5-oxytryptophan, with a precursor of dopamine levodopa, with an α2-adrenoceptor agonist clonidine, and with an agonist of M-cholinoceptors arecoline. Results. It has been shown that the spectrum of neuropharmacological effects of new derivatives of tietan-1,1-dioxide (H14, H40, N69) is diverse and is associated with the effects on the adrenergic, dopaminergic and serotonergic brain structures. Thus, H14 reduces the severity of hypothermia induced by reserpine, apomorphine, clonidine, and levodopa, as well as the severity of reserpine ptosis, haloperidol catalepsy and 5- oxytryptophan hyperkinesis. H40, in contrast to H14, has no effect on haloperidol catalepsy and hypothermia induced by levodopa, while H69 has no effect on clonidine-induced hypothermia. All the compounds do not alter the latent period and duration of the arecoline tremor. Conclusion. New derivatives of tietan-1,1-dioxide possess properties, which are inherent to antidepressants, and may be recommended for further in-depth study of their antidepressant activity.

The microsomal enzymatic system (MES) occupies, together with immune and antioxidant systems, a key position in the overall immunochemical homeostasis maintenance system [1]. The main biological role of MES consists in the oxidation of low-molecular-weight compounds, including products formed in the living cell (cholesterol, saturated and unsaturated fatty acids, prostaglandins, etc.) and substances coming into the organism from outside (drugs, toxicants, etc.) [2]. As is known, xenobiotics (including drugs) are capable of modifying the activity of MES [3]. Indeed, the induction of MES, on the one hand, stimulates its own metabolism significantly reducing the duration and expression of the pharmacological effect and, on the other hand, influences the biotransformation of other drugs administered simultaneously with such an “inductor.” Any depression of MES leads to increasing toxicity of most xenobiotics and to side effects of the usual drugs (e.g., to those observed upon the joint administration of ketoconazole and terfenadine [4]). If we take into account only the pharmacometabolizing function of the liver, assessment of the ability of compounds to control the MES function would virtually always be “negative” [4, 5]. Nevertheless, such properties may have qualitatively different characteristics. From the standpoint of MES being involved into the immunochemical homeostasis maintenance, the ability of modulating this activity must be considered as a potential means of relieving symptoms and correcting a large number of disorders [6 – 9], especially those affecting the hepatobiliary system. This statement refers to both MES depressants and activators. The metabolism of some xenobiotics proceeds by the pathway of intoxication, leading to the formation of intermediates possessing carcinogenic, mutagenic, and hepatoand/or embryotoxicity. The important role played by the induction of some isoforms of cytochrome P-450 in carcinogenesis and mutagenesis drives the search for new microsomal inhibitors as potential antidotes for procarcinogens (polycyclic aromatics, polychlorinated biphenyls, etc.) and as antitumor drugs [7]. These aspects suggest promising directions in the search for MES modulants and account for the interest of researchers studying quantitative structure – activity relationships (QSAR) for such agents using various method [10 – 13]. We have studied QSAR problems for MES activity inhibitors and inductors using a substructural approach and a SARD computer modeling system [14]. The initial information included structural data and the results of screening based on the hexenal-induced sleep test involving 208 azoles synthesized and studied at the Bashkir State Medical University (Ufa) (see, e.g., [15, 16]). All substances were conditionally divided into three classes: inductors, “indifferent substances” (neutrals), and inhibitors. This classification was based on the criterion of reliable ( p < 0.05) difference in the hexenal sleep duration – the most informative parameter ensuring in vivo evaluation of the degree of P-450b isoform induction [17] – between mice in the control and test groups. Below we report on data concerning the depressant effect of various azole derivatives on MES. The alternative groups in the learning set necessary for the QSAR analysis contained 66 azole derivatives of types I – III, including 34 MES inhibitors (acting as depressants in the hexenal sleep test) and 32 compounds exhibiting no activity in this test: Pharmaceutical Chemistry Journal Vol. 35, No. 6, 2001

6,8-Dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-f]xanthine, a new inductor of the monooxygenase system, inhibited the development of experimental intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats. The drug stimulated the detoxicating function of liver, increased the survivability of rats, restored the level of microsomal protein and cytochrome P-450, decreased the cell-average erythrocyte fragility, and reduced the activity of cholestasis markers and the amount of TBA-active products in hepatocytes.