Topical praziquantel as a new treatment for perioral dermatitis: results of a randomized vehicle-controlled pilot study.

BACKGROUND: Perioral dermatitis (POD) is a common skin disease, and extending the range of treatments available for this condition is important. AIM: To evaluate the safety, efficacy and tolerability of praziquantel 3% ointment as monotherapy. METHODS: This was a single-centre, randomized, single-blind, vehicle-controlled pilot study in adult patients (n = 46) with 4 weeks of treatment and 4 weeks of follow-up. Efficacy was assessed clinically using the Investigator's Global Assessment (IGA) and the Perioral Dermatitis Severity Index (PODSI). Quality of life (QOL) was determined by the Dermatology Quality of Life Index (DLQI). RESULTS: PODSI was significantly lower in the praziquantel group than in the placebo (vehicle) group, both during treatment and period. Mean IGA score showed a statistically significant therapeutic advantage of praziquantel over placebo at week 4 (P < 0.001). The praziquantel group experienced a greater improvement in mean DLQI. No serious treatment-related adverse events occurred in either group. CONCLUSIONS: Praziquantel ointment 3% effectively improves POD symptoms and QOL.

[The spectrum of CLCN1 gene mutations in patients with nondystrophic Thomsen's and Becker's myotonias].

Thomsen's and Becker's diseases are the most prevalent nondystrophic myotonias. Their frequency varies, according to different sources, from 1 : 100 000 to 1 : 10 000. Thomsen's myotonia is autosomal dominant, and Becker's myotonia is autosomal recessive. Both diseases result from mutations of the CLCN1 gene encoding chloride ion channels of skeletal muscles. Molecular genetic analysis of the CLCN1 gene has been performed in patients with diagnoses of nondystrophic Thomsen's and Becker's myotonias living in the Russian Federation. A sample of 79 unrelated probands with nondystrophic Thomsen's and Becker's myotonias and 44 their relatives has been formed in the Laboratory of DNA Diagnosis of the Medical Genetic Research Center of the Russian Academy of Medical Sciences. Forty CLCN1 gene mutations have been found in a total of 118 chromosomes of 66 probands, including 21 familial and 45 sporadic cases. About half the mutations detected (45%) have been found for the first time; they are not described in the SNP database (ncbi.nlm.nih.gov). The following mutations (substitutions) have been detected in more than one chromosome, accounting for a total of 59.3% of chromosomes with mutations: Glyl90Ser (5.9%), c.1437-1450del14 (9.3%), Ala493Glu (5.1%), Thr550Met (3.4%), Tyr686Stop (5.1%), and Arg894Stop (30.5%).

[Genetic epidemiological study of Bashkortostan Republic: the diversity of monogenic hereditary diseases in five districts].

The diversity of monogenic hereditary diseases (HDs) (autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases) has been studied in five districts of Bashkortostan Republic: Burzyanskii, Abzelilovskii, Baimak, Salavatskii, and Arkhangel'skoe raions. The spectrum of HDs comprised 144 diseases, including 83, 48, and 13 Ad, AR, and X-linked diseases. Most of them were found earlier during studies in ten other regions of Russia (Kirov, Kostroma, Tver', Bryansk, and Rostov oblasts, and Krasnodar krai, and the republics of Adygea, Marii El, Udmurtia, and Chuvashia). Foci of local accumulation of some AD, AR, and X-linked diseases have been found in individual districts. Data on the gene frequencies for the HDs have been used for cluster analysis, which has shown the gene geographic position of Bashkirs among nine ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), Udmurts (Udmurtia), and Bashkirs (Bashkortostan).

[Genetic epidemiological study of Bashkortostan Republic: the effect of genetic structure of population on the load of monogenic hereditary diseases].

Here we present the data obtained during medical genetic examination of the population of five districts of Bashkortostan Republic (Burzyanskii, Baimakskii, Abzelilovskii, Salavatskii, and Arkhangelskii) populated with 168050 persons including 135748 Bashkirs. The study involved all the population of the districts including each ethnic group and was conducted according to standard protocol developed in the Laboratory of Genetic Epidemiology, Medical Genetic Research Center, Russian Academy of Medical Sciences. Based on segregation analysis, the values of prevalence rates of the major types of Mendelian pathology (AD, AR, and X- linked diseases) was calculated in five regions of the Republic as well as for Bashkirs alone. Significant differences in the prevalence rates of AD and AR pathologies between individual districts, in particular upon division in rural and urban population, was observed. The prevalence rates comparison of monogenic hereditary pathology among Bashkirs compared to other previously examined populations have shown that the patterns of the hereditary disease load in the inspected districts of Bashkortostan were similar to that observed in the population of some districts in Udmurtia, Marii El and Chuvashiya. Russian European populations have shown significantly lower load of hereditary diseases. Correlation analysis of local inbreeding, endogamy and prevalence rates of AD and AR pathologies has shown that development of hereditary diseases load is significantly affected by gene drift.

[Systems of chemoperception in decapod crayfish].

The review presents data on some peripheral and central structures in the system of perception of chemical stimuli in crayfish and other Decapoda. The hair receptors on chelipeds, antennas, antennules are innervated by mechano-and chemoreceptor neurons. Antennules are the specialized crayfish chemoreceptor organs, on the surface of which groups of exteroceptors are located. There is an ordered disposition of exteroceptor receptive fields in the form of receptor hair bushes on claws of ambulatory feet (AF), antennas, antennules, and other movable appendages. Behavioral experiments have shown sensitivity of crayfish to odor of individuals of their gender, sex partners as well as the presence in crayfish of pheromones providing connection of female with offspring at the initial stages of the life cycle. Occasional chemosensory cells innervating hair bushes on the crayfish AF respond to amino acids, amines, nucleotides, and sugars. Minimal thresholds of reaction of the studied Decapoda chemoreceptors in response to some chemical compounds correspond to concentrations of 0.1-1 microM. For some chemoreceptors, dose-dependent effects have been shown. Alongside with monomodal chemoreceptors, the crayfish have bimodal receptor perceiving mechanical and chemical stimuli. The efficient response of crayfish chemoreceptors can be obtained to the substance that includes amino group with the hydrogen bridge with carboxyl group, contains no more than 3 carbon atoms in the chain, and is characterized by a certain stereoform. Among chemoreceptors there are fast and slow adapting cells. Efficiency of response of individual chemoreceptors depends on temperature of medium. Chemoreceptors reacting to ecdysterons have been revealed in crayfish. Ecdysterons play a great role in intra- and interspecies communications in Crustacea. Based on the study of efferent responses of interneurons of the first and higher orders in the first thoracic crayfish ganglion to stimulation of the own receptive fields, a concept is put forward of the structural-functional organization of afferent projections at the segmental level. Peculiarities of afferent projections from antennule chemoreceptors are considered. The data are presented on connections of these chemoreceptors with antennular, olfactory, and additional lobules, various cell groups, interneurons of the first, second, and third orders located in various brain parts. An attention is drawn to connections of serotonin neurons in glomeruli with endings of chemoreceptor neurons and projection of interneurons of the higher orders,. which are located in the internal medulla of the crayfish eye stalks. Several principles of integration of the chemoreceptor information in central parts of the crayfish nervous system are discussed. The giant serotonin neurons revealed in crayfish glomeruli most likely participate in formation of memory to certain chemical actions. Polymodal receptor signals in the central chain of the perception system activate autonomic centers, and the changes of the animal functional state can be evaluated from the heart responses. The crayfish heart responses recorded by novel noninvasive methods allow detection of the initial and other phases of the stress state at changes of the chemical quality of medium. Progress of the current biochemical and electrophysiological methods of study of chemoreceptors allow hoping for learning of fine chemoperception mechanisms in invertebrate and vertebrate animals.

[Molecular analysis of the Y chromosome in XX sex-reversed patients].

Molecular genetic analysis was performed for 26 phenotypically male patients lacking the Y chromosome in the karyotype. The sex-determining region Y (SRY) gene was found in 77% of the patients. PCR analysis of Y-specific loci in the 17 SRY-positive patients revealed Yp fragments varying in size in 16 cases and cryptic mosaicism (or chimerism) for the Y chromosome in one case. The frequencies of class I, II, and III (Yp+)XX sex reversals were 18.75, 25.25, and 56%, respectively. All of the class III (Yp+)XX sex-reversed patients had a 3.5-Mb paracentric inversion flanked by inverted repeats 3 (IR3) on the short arm of the Y chromosome.

A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21.

Charcot-Marie-Tooth disease (CMT) constitutes a genetically heterogeneous group of inherited motor and sensory peripheral neuropathies. The axonal type of CMT is designated CMT type 2 (CMT2). Four loci for autosomal dominant CMT2 have been reported so far. Only in CMT2E, linked to chromosome 8p21, disease-causing mutations in the gene for neurofilament light chain (NEFL) were identified. In this study we report a multigenerational Russian family with autosomal dominant CMT2 and assign the locus to chromosome 7q11-q21. The CMT2 neuropathy in this family represents a novel genetic entity designated CMT2F.

[Natural peptides and their analogs. XXXI. Synthesis and properties of the retro-analog of methionine-5-enkephalin]. / Prirodnye peptidy i ikh analogi. XXXI. Sintez i izuchenie svoistv retroanaloga metionin-5-énkefalina.

The synthesis of retro-analog of methionine-5-enkephalin was performed. This peptide is an isomer of the natural methionine-5-enkephalin, but differs from it by opposite direction of peptide linkages between the amino acid residues. The influence of retro-analog on prolactin secretion was studied both in vivo and in vitro. The retro-analog was found to stimulate the prolactin secretion more effectively than methionine-5-enkephalin.

[A new structural analog of human insulin-- [glutamine-B30] insulin]. / Novyi strukturnyi analog insulina cheloveka--[glutamin-B30] insulin.

A new structural analogue of human insulin, [glutamine-B30]insulin, has been prepared by enzymatic-chemical means. This analogue differs from natural hormone by substitution of the ThrB30 residue. Biological activity of the [glutamine-B30]insulin is 100% in the mouse convulsion assay.

[Natural peptides and their analogs. XXXV. Synthesis and properties of [Ala5, Orn9]somatostatin]. / Prirodnye peptidy i ikh analogi. XXXV. Sintez i svoistva [Ala5, Orn9]somatostatina.

A total chemical synthesis of [Ala5, Orn9]somatostatin has been performed. This structural analogue of natural somatostatin inhibits the release of somatotropin, insulin and glucagon, but shows no inhibitory effect on secretion of prolactin.

[Stimulation by insulin of DNA synthesis in cultured mouse fibroblasts]. / Stimuliatsiia insulinom sinteza DNK v kul'tiviruemykh myshinykh fibroblastakh

With the aid of autoradiography, the effect of insulin on entering S- from G1-period of the mitotic cycle and on the rate of DNA synthesis of the mouse fibroblasts (L), was studied,--in the cells incubated for 24 hr in serum-free medium. In these conditions the cells were temporarily blocked in G1-period. Insulin (100 mcU/ml) increased by 1.5-fold the amount of cells in S-period as well as caused a marked stimulation of DNA synthesis.

[Nozological spectrum of hereditary diseases of the nervous system in the cities of Volgograd and Volzhsky]. / Nozologicheskii spektr nasledstvennykh boleznei nervnoi sistemy v gorodakh Volgograd i Volzhskii.

A spectrum of hereditary diseases of the nervous system (HDNS) was studied in the cities of Volgograd and Volzhsky. The estimates were obtained for the prevalence of major HDNS groups and individual nosological forms. The populations examined differed in prevalence of this pathology and in contribution of individual diseases and their nosological forms into HDNS load formation. The effect of the population dynamics in Volgograd and Volzhsky on the HDNS prevalence is discussed.

[Genetic and epidemiologic analysis of hereditary diseases of the nervous system in the cities of Volgograd and Volzhskii]. / Genetiko-épidemiologicheskoe issledovanie nasledstvennykh boleznei nervnoi sistemy v gorodakh Volgograd i Volzhskii.

A genetic epidemiological study of hereditary diseases of the nervous system (HDNS) was conducted in the cities of Volgograd and Volzhsky for the first time. In total, 1 323 500 individuals were examined including the populations of Volgograd and Volzhsky (1 012 800 and 310 700 persons, respectively). The prevalence of neurological diseases with autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive inheritance was estimated. These data were compared with the estimates previously obtained for different population of the Russian Federation. A decrease was found in general HDNS load in Volgograd and Volzhsky. The compared populations were shown to differ in a contribution of AD, AR, and X-linked recessive diseases into the HDNS load formation. The possible effect of population dynamics factors on the HDNS load structure is discussed.

[Automatic analysis of needle EMG in the differential diagnosis of neuromuscular diseases]. / Avtomaticheskii analiz igol'chatoi EMG v differentsial'noi diagnostike nervno-myshechnykh zabolevanii.

A total of 112 muscles were studied in 68 patients with different neuromuscular diseases (7 nosological forms). The study was performed using an original programme of an automatic analysis of needle real-time electromyography and a specially designed automatic system on the basis of Soviet microcomputer "Electronika-60". On the basis of an automatic analysis of 17,834 potentials the authors identified 1,619 individual potentials of motor units. Measurement of all parameters (amplitude, duration, the number of phases in the potential and area) and calculation of correlations between individual parameters revealed significant differences of the mean values of the above parameters for each group of patients.

[Estrogenic and contraceptive activity of 17-R-hydroximino derivatives of 9alpha-hydroxy-11beta-nitroxyestrones]. / Estrogennaia i kontratseptivnaia aktivnost' 17-R-oksiminoproizvodnykh 9alpha-oksi-11beta-nitroksiéstronov.

The estrogenic or uterotropic (UA) and contraceptive (CA) activity of two modified steroids representing 17-R-oximino-9 alpha-oxy-11 beta-nitroxyestrone derivatives (compounds I and II) was experimentally studied by oral administration in female rats in comparison to ethynylestradiol (EED) and mestranol. Compounds I and II showed significant UA (about half that of EED and mestranol) and a pronounced contraceptive effect (exceeding that of mestranol). The dissociation of the drug effects for CA is also indicated by the index of contraception (IC) or the CA/UA ratio. The administration of compounds I and II did not lead to a loss of animals in the acute toxicity tests on female mice.

[The effect of C-ring transformed estrogens on the reproductive system]. / Vliianie transformirovannykh po kol'tsu C éstrogenov na reproduktivnuiu sistemu.

Comparative study of the effect of two groups of C-ring transformed oestrogens on the reproductive system was conducted in experiments on female rats. 11-Nitrate-9 alpha, 11 beta-dioxyethynylestadiols (I-IV), 11-nitrate-9 alpha-oxyesterons (V-VII), and 11 formiate-11 beta-oxyethynylstadiol (VIII) were given per os to the rats. As compared to ethynylestradiol (EE), compounds I-IV demonstrated 4-10 times higher oestrogenic activity and 11-23 times higher contraceptive activity. 11-Nitrate (V-VII) proved to be less active oestrogens (77-91% of EE activity) but its contraceptive effect was equal to or exceeded that of EE. The oestrogenic activity of 11-formiate (VIII) was three times higher than that of EE, but its contraceptive effect was only 50% of the effect of EE. The higher contraceptive effect of compounds I-IV in comparison to their oestrogenic activity allows these oestrogens to be considered perspective substituents of EE among the oral contraceptives. In oral administration of compound I alone or compounds I and IV together with gestagen acetomepregenol (AMP), inhibition of luteinizing hormone release was stronger and more prolonged than in administration of EE alone or in combination with AMP. This effect may be considered to be one of the possible mechanisms of the activity of 11-nitrate oestrogens.

[The pharmacological properties of a modified estrogen 11-nitrate-3-acetate-9 alpha, 11 beta-dioxyestrone]. / Izuchenie nekotorykh farmakologicheskikh svoistv modifitsirovannogo éstrogena 11-nitrat-3-atsetat-9 al'fa, 11 beta-dioksiéstrona.

The experiments on 715 adult non-inbred female rats and 111 Wistar male rats have established that the estrogen 11-nitrate of 3-acetoxy-9 alpha,11 beta-dioxyestra-1,3,5(10)-trien-17-one (11-nitrate of dioxyestron (NDE-As) has an oral contraceptive activity which is equal to ethynylestradiol (EE). A combined 14-day administration of NDE-As with various gestagens produces a higher contraceptive effect that does EE used in combination with the same gestagens. A 30-day use of NDE-As with combined acetomepregenol (AMP) results in a more significant and prolonged secretion of luteinizing hormone than does the EE-AMP combination. Unlike ethynylestradiol, NDE-As has no hypertriglyceridemic effect when given in oral doses of 0.25 and 1.25 mg/kg body weight.

[Effect of sensory input parameters on efferent output of spike activity of river crayfish neurons]. / Vliianie parametrov sensornogo vkhoda na éfferentnyi vykhod impul'snoi aktivnosti neironov rechnykh rakov.

Studies have been made of the influence of localization, direction, frequency and other parameters of mechanostimulation of the cuticular receptors on the impulse activity of efferent neurones innervating claw muscles in the crayfish Astacus astacus and A. leptodactylus. The results obtained are discussed from a standpoint of the possibility of central organization of sensory-motor relationships, which involves modulating afferent influences on efferent neuronal activity.

[The effect of insulin on protein synthesis and secretion in primary liver cultures]. / Vliianie insulina na sintez i sekretsiiu belkov v pervichnykh kul'turakh kletok pecheni.

The effects of insulin on the rates of synthesis of intracellular and secreted proteins have been studied in primary cultures of fetal rat hepatocytes. During 3-h incubation with the hormone and 14C-L-leucine similar stimulation of synthesis of both intracellular and secreted protein was observed. Insulin did not affect significantly the proportion of 14C-labelled proteins destined for secretion in the cell cultures grown on standard nutrient medium, as well as on selective medium containing phenobarbital and cortisol. The results obtained show that the major part (85-90%) of newly synthesized proteins remains inside the cells. Therefore, biological testing of insulin or its synthetic analogs on hepatocyte cultures may be limited by the estimation of the rate of biosynthesis of intracellular proteins only.

[Reactions of rat fetal hepatocytes to hormones in primary cultures grown in selective media with an addition of glucocorticoid and barbiturate]. / Reaktsii gepatotsitov plodov krys na gormony v pervichnykh kul'turakh vyrashchennykh v selektivnoi srede s dobavleniem gliukokortikoida i barbiturata.

After growing of fetal rat hepatocytes in the medium containing cortisol and sodium barbital for 4-8 days and subsequent cultivation in the medium without glucocorticoid and barbiturate for 1-4 days insulin retained its ability to stimulate total RNA and protein synthesis, while human growth hormone kept its enhancing action on RNA biosynthesis. However, cortisol did not change protein synthesis and inhibited paradoxically incorporation of 3H-uridine into total RNA, after preincubation of cells in the selective medium. This suggests that prolonged exposure of cultured fetal rat liver cells to cortisol and sodium barbital may cause phenomena similar to those of hormonal and/or enzymatic imprinting.