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%).

[Clinical-genetic correlations in the hereditary motor-sensor neuropathy caused by mutations in the MPZ (P0) gene].

Hereditary motor-sensor neuropathy (HMSN) caused by mutations in the MPZ (P0) gene is a rare variant of hereditary demyelinating polyneuropathies that makes up 5-10% of all cases in different populations. Based on the complex examination of patients of the Russian Federation with different MPZ (P0) mutations, we obtained clinical-genetic, electromyographic and molecular-genetic characteristics of HMSN caused by mutations in the MPZ (P0) gene. Peculiarities of clinical presentations in patients with HMSN, types 1B and 2I, are presented. Diagnostic criteria of these genetic variants have been formed. The new allelic variants of HMSN caused by mutations in the MPZ (P0) gene are described. The distribution of mutations by protein domains has been analyzed.

[Clinical-genetic characteristics of limb girdle-muscular dystrophy type 2A].

We present the results of the molecular genetic study of 26 patients, aged from 12 to 60 years, from 24 unrelated families with limb girdle-muscular dystrophy (LGMD) type 2A. The disease duration varied from 6 months to 30 years. The diagnosis of LGMD 2capital A, Cyrillic was confirmed by molecular genetic methods basing on the presence of a CAPN3 mutation in homozygous, compound-heterozygous and heterozygous state. The Leyden-Moebius variant that is characterized by the primary affection of muscles of pelvic girdle and shin with the gradual progression of the pathological process in shoulder girdle muscles was the most frequent in the Russian population. Tip-toe walking or difficulties in walking upstairs and running were the first symptoms reported by patients. In contrast to criteria of the European Neuromuscular Center, the characteristic symptoms of the disease were early contractures of ankle joints and pseudohypertrophy of gastrocnemius muscles. The major c.550delA mutation in the CAPN3 gene was identified in 70% of Russian patients.

[Hereditary spastic paraplegia type 4 (SPG4): clinical and molecular-genetic characteristics].

Hereditary spastic paraplegia (HSP), type 4, or SPG4, caused by various mutations in the spastin gene (SPAST) is the most common disorder in a heterogeneous group of autosomal dominant HSP's. We performed a search of SPAST mutations by routine methods (SSCP and subsequent direct sequencing of fragments with modified electrophoretic mobility) in a sample of 26 families with autosomal dominant HSP from different Russian regions. In six families, five of Russian and one of Tatar ethnicity, different SPAST mutations were detected. Three of the mutations, Arg431Stop, Gln280Arg FsX9 and Asn386Ser, were reported previously; the remaining three, Asp555Tyr, Thr369Thr and Asn184Thr, were novel. In the family with the Arg431Stop mutation, a linkage to SPG4 locus was also established, lod scores were 1,66 for D2S352 marker and 1,51 for D2S367. Another large family also showed a linkage to the SPG4 locus (lod scores 1,68 for D2S352, 2,17 for D2S367) but the mutation was not found which may be due to atypical SPAST mutations (large deletions etc) undetectable by routine methods of DNA analysis. Including this family, the proportion of the SPG4 in the sample is 27%, which is less than average literature data (40-45%). Most of our patients presented relatively late-onset "uncompicated" HSP, which was typical for SPG4, though different additional features in SPG4 patients were also known. One of our patients had very early-onset HSP and concomitant epilepsy. In two pedigrees, in which all available relatives were examined, some patients had mild signs of SPG4, even late in life.

[Hereditary motor and sensory neuropathy type 4A].

The first in the Russian Federation clinical cases of patients with autosomal-recessive type of hereditary motor and sensory neuropathy, type 4A, (HMSN 4A) are presented. In all cases, the diagnosis has been verified using molecular-genetic methods (DNA diagnostics). An analysis of features of clinical manifestations was performed in patients, aged from 5 to 34 years, with different disease duration (from 3-to 29 years). Criteria of selection of patients for DNA diagnostics for searching mutations in the GDAP1 gene are specified.

[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.

[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).

[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.

[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.

[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.

[Diagnosis and principles of complex therapy of sarcoidosis]. / Diagnostika i printsipy kompleksnoi terapii sarkoidoza.

The diagnosis and therapy of 87 patients with sarcoidosis admitted to the Central Military Clinical Tubercular Hospital were analyzed. The diagnosis was based on the data of clinicoroentgenologic investigation and histologic examination of the specimen taken from the affected tissue. The differential diagnosis with tuberculosis is obligatory. The complex therapy includes corticosteroids, antioxydants, phytotherapy, physiotherapeutic methods and in some cases plasmapheresis.

[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.

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.