RESUMO
The hEag1 (Kv10.1) K+ channel is normally found in the brain, but it is ectopically expressed in tumor cells, including osteosarcoma. Based on the pivotal role of ion channels in osteogenesis, we tested whether pharmacological modulation of hEag1 may affect osteogenic differentiation of osteosarcoma cell lines. Using molecular biology (RT-PCR), electrophysiology (patch-clamp) and pharmacology (astemizole sensitivity, IC50 = 0.135 µM) we demonstrated that SaOS-2 osteosarcoma cells also express hEag1 channels. SaOS-2 cells also express to KCa1.1 K+ channels as shown by mRNA expression and paxilline sensitivity of the current. The inhibition of hEag1 (2 µM astemizole) or KCa1.1 (1 mM TEA) alone did not induce Ca2+ deposition in SaOS-2 cultures, however, these inhibitors, at identical concentrations, increased Ca2+ deposition evoked by the classical or pathological (inorganic phosphate, Pi) induction pathway without causing cytotoxicity, as reported by three completer assays (LDH release, MTT assay and SRB protein assay). We observed a similar effect of astemizole on Ca2+ deposition in MG-63 osteosarcoma cultures as well. We propose that the increase in the osteogenic stimuli-induced mineral matrix formation of osteosarcoma cell lines by inhibiting hEag1 may be a useful tool to drive terminal differentiation of osteosarcoma.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Astemizol/farmacologia , Linhagem Celular Tumoral , Canais de Potássio Éter-A-Go-Go , Humanos , Osteogênese , Osteossarcoma/tratamento farmacológico , Fosfatos/metabolismo , RNA Mensageiro/genéticaRESUMO
The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G-quadruplexes) can lead to replication fork stalling. G-quadruplexes (G4s) are well-characterized stable secondary DNA structures that can form within specific single-stranded DNA sequence motifs and have been shown to block/pause the replication machinery. In most genomes several helicases have been described to regulate G4 unfolding to preserve genome integrity, however, different experiments raise the hypothesis that processing of G4s during DNA replication is more complex and requires additional, so far unknown, proteins. Here, we show that the Saccharomyces cerevisiae Mgs1 protein robustly binds to G4 structures in vitro and preferentially acts at regions with a strong potential to form G4 structures in vivo. Our results suggest that Mgs1 binds to G4-forming sites and has a role in the maintenance of genome integrity.
Assuntos
DNA Helicases/fisiologia , Proteínas de Ligação a DNA/fisiologia , Quadruplex G , Instabilidade Genômica , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/genética , DNA Fúngico/química , Ligação ProteicaRESUMO
The immunological synapse (IS) is a specialized contact area formed between a T cell and an antigen presenting cell (APC). Besides molecules directly involved in antigen recognition such as the TCR/CD3 complex, ion channels important in the membrane potential and intracellular free Ca2+ concentration control of T cells are also recruited into the IS. These are the voltage-gated Kv1.3 and Ca2+-activated KCa3.1 K+ channels and the calcium release-activated Ca2+ channel (CRAC). However, the consequence of this recruitment on membrane potential and Ca2+ level control is not known. Here we demonstrate that the membrane potential (MP) of murine T cells conjugated with APCs in an IS shows characteristic oscillations. We found that depolarization of the membrane by current injection or by increased extracellular K+ concentration produced membrane potential oscillations (MPO) significantly more frequently in conjugated T cells than in lone T cells. Furthermore, oscillation of the free intracellular Ca2+ concentration could also be observed more frequently in cells forming an IS than in lone cells. We suggest that in the IS the special arrangement of channels and the constrained space between the interacting cells creates a favorable environment for these oscillations, which may enhance the signaling process leading to T cell activation.
Assuntos
Sinalização do Cálcio , Sinapses Imunológicas/metabolismo , Potenciais da Membrana , Linfócitos T/metabolismo , Animais , Células Apresentadoras de Antígenos/metabolismo , Células Apresentadoras de Antígenos/fisiologia , Cálcio/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Linhagem Celular , Sinapses Imunológicas/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Canal de Potássio Kv1.3/metabolismo , Camundongos , Potássio/metabolismo , Linfócitos T/fisiologiaRESUMO
OBJECTIVE: We report the infection of New Zealand white rabbits with Epstein-Barr virus (EBV). METHODS: EBV prepared in B95-8 (producer) cells was inoculated to rabbits by combined intranasal and oral routes. Blood and white blood cell (WBC) samples were taken before infection, then on days 8, 28 and 98 post-infection (p.i.). RESULTS: Administration of either 3 × 10(8) (group A, 11 rabbits) or 1 × 10(9) (group B, 10 rabbits) EBV DNA copies per animal induced subacute and/or persistent infection. The IgG antibodies in plasma were detected by ELISA as well as by immunoblot (IB). The IB bands showed mainly antibodies to the BZRF1/Zta transactivation polypeptide (69.2%), the p54 early protein (53.4%) and to the p23 capsid protein (35.8%). No anti-EBNA1 antibody was detected throughout. Viral DNA could be detected by PCR in WBCs and/or spleen of 7 out of 21 infected rabbits (30%), while 60-80% of them showed serologic response. The transiently present EBV DNA was accompanied by LMP1 antigen. CONCLUSIONS: Rabbits developed persistent EBV infection in the absence of EBNA1 antibodies and by the lack of typical infectious mononucleosis-like syndrome. The absence of EBNA1 antibody may reflect the lack of EBNA1 in B cells of EBV-inoculated rabbits.
Assuntos
Modelos Animais de Doenças , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/crescimento & desenvolvimento , Leucócitos Mononucleares/patologia , Animais , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Herpesvirus Humano 4/imunologia , Humanos , Immunoblotting , Imunoglobulina G/sangue , Mononucleose Infecciosa/patologia , CoelhosRESUMO
Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase.
Assuntos
DNA Helicases , Replicação do DNA , Quadruplex G , Humanos , DNA Helicases/metabolismo , Dano ao DNA , Aberrações Cromossômicas , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genéticaRESUMO
Due to their complex life cycles geophytes are often neglected in conservation programs, despite they are important elements of early spring communities. Their life cycle is strongly affected by weather parameters, i.e. temperature, precipitation, and light, but the effects of these parameters are often contradictory and show high intra-annual variability even within species. Deeper knowledge about the abiotic factors affecting the population dynamics of geophytes is needed to support the designation of effective conservation plans. We aimed to explore the link between weather parameters and population dynamics of Colchicum bulbocodium, an endangered and strictly protected geophyte. We monitored three life cycle stages (flowering, growing, fruiting) of 1069 individuals in permanent plots for six consecutive years. Our results showed that life cycle of C. bulbocodium was strongly related to the actual weather parameters; the lagged effect of the previous year was weaker. Increasing temperature and lack of cold periods had negative effect on all life stages. We highlighted that population estimation based on the number of flowering individuals in a single year can underestimate population size by 40-83%. Monitoring in years following wet and cold springs and cold winters could increase the accuracy of population estimations of the flowering individuals.
Assuntos
Espécies em Perigo de Extinção , Dinâmica Populacional , Tempo (Meteorologia) , Estações do Ano , TemperaturaRESUMO
We performed a comparative study on the development of mastitis induced by Mycoplasma arginini or Streptococcus dysgalactiae after challenging the cows. Mycoplasma arginini did not cause any clinical symptoms on its own, resulting in only a transient increase of somatic cell count (SCC; increase ranging from 0.5 × 10(6) to 0.8 × 10(6) cells/mL) and a slight decrease of milk production (10%) for 5 d. In contrast, Strep. dysgalactiae induced more severe clinical signs in animals and SCC increased to 1.60 × 10(6) to 2.11 × 10(6) cells/mL for 10 d. In addition, milk production decreased (22.9 to 27.0%) for 10 d. After 3 mo (2 mo after the first challenge), animals that were challenged previously with M. arginini were rechallenged with Strep. dysgalactiae. Severe clinical mastitis developed, with very high SCC (5.00 × 10(6) to 21.5 × 10(6) cells/mL), and a very significant reduction of milk production (28.6 to 68.7%), which lasted more than 4 wk, was observed. The severe clinical mastitis developed not only in cows inoculated with Strep. dysgalactiae andM. arginini in the same udder quarter but also in cows infected in the quarter previously not challenged with mycoplasma. Cows challenged first with Strep. dysgalactiae and rechallenged with M. arginini 2 mo later developed only slight changes in both SCC and milk production, similar to those when the cows were challenged with M. arginini alone. We conclude that M. arginini infection does not cause remarkable mastitis (characterized by decrease in milk production and increase of SCC) but it significantly predisposes animals to infection with Strep. dysgalactiae, leading to severe clinical mastitis.
Assuntos
Mastite Bovina/microbiologia , Infecções por Mycoplasma/veterinária , Mycoplasma , Infecções Estreptocócicas/veterinária , Streptococcus , Animais , Bovinos , Coinfecção/microbiologia , Coinfecção/veterinária , Feminino , Lactação , Leite/citologia , Infecções por Mycoplasma/microbiologiaRESUMO
Local biodiversity hotspots are often located within regions where extreme and variable environmental - e.g., climatic and soil - conditions occur. These areas are conservation priorities. Although environmental heterogeneity is recognised as an important determinant of biodiversity, studies focusing on the effects of multiple environmental heterogeneity components in the same ecosystem are scarce. Here we investigate how topography and related microclimatic variables and soil properties may influence the biodiversity and conservation value of karst landscapes. Karst landscapes of the world contain millions of dolines (i.e. bowl- or funnel-shaped depressions) that may function as 'small natural features' with a disproportionately large role in maintaining biodiversity relative to their size. We assessed the diversity of microclimates, soils and vegetation and their relationships in six microhabitats (south-facing slopes, east-facing slopes, west-facing slopes, north-facing slopes and bottoms of dolines, and the adjacent plateau) for nine large dolines in a grassland ecosystem. Although there were remarkable differences among the conservation value of these microhabitats (e.g., representation of different species groups, presence of 'climate relicts'), each microhabitat had an important role in maintaining species that are rare or absent in other microhabitats in the landscape. We found that the studied dolines exhibited highly variable environmental conditions and promoted a high diversity of vegetation types with unique species composition, contributing to the topographic, climatic, soil, vegetation and land cover heterogeneity of karst landscapes. Therefore, our findings highlight that dolines may function as local biodiversity hotspots and have a crucial conservation importance. As dolines are widespread topographic features in many karst landscapes throughout the world, our results could be directly applied to other regions as well. An integrated approach is urgently needed to provide guidelines for landscape management, promoting the retention of the microhabitat diversity of small natural features for species vulnerable to climate change and/or various disturbances.
Assuntos
Biodiversidade , Ecossistema , Solo , Mudança Climática , Conservação dos Recursos Naturais/métodosRESUMO
Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood-brain barrier.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndrome de Lesch-Nyhan/terapia , Bussulfano/uso terapêutico , Desenvolvimento Infantil , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Ciclofosfamida/uso terapêutico , Distonia/etiologia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Humanos , Hipoxantina Fosforribosiltransferase/sangue , Imunossupressores/uso terapêutico , Síndrome de Lesch-Nyhan/psicologia , Masculino , Mucosite/etiologia , Mucosite/patologia , Espasticidade Muscular/etiologia , Neutropenia/etiologia , Comportamento Autodestrutivo/etiologia , Comportamento Autodestrutivo/terapiaRESUMO
Sowing is widely used for the restoration of species-rich grasslands but still there are knowledge gaps regarding the most suitable application of different seed mixtures. We tested the effect of seed mixtures application timing on the establishment of sown forbs and weed control. 36 experimental plots with nine sowing treatments were established in an abandoned cropland in Hungary. Grass-seeds, diverse forb seed mixture and the combination of the two were applied: diverse forb mixture was sown simultaneously or 1, 2 or 3 years after grass sowing, in plots sown previously with grass or in empty plots (fallows). All sowing treatments supported the rapid establishment of the sown species in large cover and hampered weed encroachment. Forbs performed better when sown into fallows than in grass-matrix and forbs establishment was worse in older fallows than in younger ones. Grasses expressed a strong priority effect, especially when forbs were sown at least two years later than grasses. We also investigated the relation between seed germinability, weather parameters and establishment success. Germination rate in the greenhouse could not predict the establishment success of forbs in the field and showed great differences between years, hence we recommend sowing target forbs in multiple years.
Assuntos
Poaceae , Controle de Plantas Daninhas , HungriaRESUMO
Background: Soil seed banks play a central role in vegetation dynamics and may be an important source of ecological restoration. However, the vast majority of seed bank studies examined only the uppermost soil layers (0-10 cm); hence, our knowledge on the depth distribution of seed bank and the ecological significance of deeply buried seeds is limited. The aim of our study was to examine the fine-scale vertical distribution of soil seed bank to a depth of 80 cm, which is one of the largest studied depth gradients so far. Our model systems were alkaline grasslands in East-Hungary, characterised by harsh environmental conditions, due to Solonetz soil reference group with Vertic horizon. We asked the following questions: (1) How do the seedling density and species richness of soil seed bank change along a vertical gradient and to what depth can germinable seeds be detected? (2) What is the relationship between the depth distribution of the germinable seeds and the species traits? Methods: In each of the five study sites, four soil cores (4 cm diameter) of 80 cm depth were collected with an auger for soil seed bank analysis. Each sample was divided into sixteen 5-cm segments by depth (320 segments in total). Samples were concentrated by washing over sieves and then germinated in an unheated greenhouse. Soil penetration resistance was measured in situ next to each core location (0-80 cm depth, 1-cm resolution). We tested the number and species richness of seedlings observed in the soil segments (N = 320), using negative binomial generalized linear regression models, in which sampling layer and penetration resistance were the predictor variables. We ran the models for morphological groups (graminoids/forbs), ecological groups (grassland species/weeds) and life-form categories (short-lived/perennial). We also tested whether seed shape index, seed mass, water requirement or salt tolerance of the species influence the vertical distribution of their seed bank. Results: Germinable seed density and species richness in the seed bank decreased with increasing soil depth and penetration resistance. However, we detected nine germinable seeds of six species even in the deepest soil layer. Forbs, grassland species and short-lived species occurred in large abundance in deep layers, from where graminoids, weeds and perennial species were missing. Round-shaped seeds were more abundant in deeper soil layers compared to elongated ones, but seed mass and ecological indicator values did not influence the vertical seed bank distribution. Our research draws attention to the potential ecological importance of the deeply buried seeds that may be a source of recovery after severe disturbance. As Vertisols cover 335 million hectares worldwide, these findings can be relevant for many regions and ecosystems globally. We highlight the need for similar studies in other soil and habitat types to test whether the presence of deep buried seeds is specific to soils with Vertic characteristics.
Assuntos
Ecossistema , Solo , Pradaria , Banco de Sementes , Sementes , Plântula , Plantas DaninhasRESUMO
Exploration of construction, function and interaction of human growth hormone and growth hormone receptor in details resulted in the innovation of the new growth hormone receptor antagonist, pegvisomant. Pegvisomant with different mechanism of action extended the tools of medical management of acromegaly. Importance of the novel treatment modality is high. In one hand the necessity of the strict control of growth hormone/insulin-like growth factor-I axis has been proven regarding the mortality of the disease. On the other hand, despite the use of all current modes of treatment (surgery, radiotherapy, dopamine agonists, somatostatin analogs), a significant cohort of patients with acromegaly remains inadequately controlled. Pegvisomant has been registered in 2004. Since 2006, it has been used in Hungary for the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. Clinical use of pegvisomant in the treatment of acromegaly is effective, well tolerated, and safe, based on international Acrostudy database. In order to improve the efficacy of therapy clinical trials started with pegvisomant and somatostatin analog combination treatment. Evidence of several further effects of the growth hormone/insulin-like growth factor-I axis suggests other potential uses of growth hormone receptor antagonists.
Assuntos
Acromegalia/tratamento farmacológico , Adenoma/terapia , Hormônio do Crescimento Humano/análogos & derivados , Proteínas de Membrana/antagonistas & inibidores , Neoplasias Hipofisárias/terapia , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/etiologia , Acromegalia/metabolismo , Adenoma/complicações , Adenoma/metabolismo , Sequência de Aminoácidos , Quimioterapia Adjuvante , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hungria , Dados de Sequência Molecular , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Radioterapia AdjuvanteRESUMO
Regioselective vicinal diamination of carbon-carbon double bonds with two different amines is a synthetic challenge under transition metal-free conditions, especially for the synthesis of trifluoromethylated amines. However, the synthesis of ethylene diamines and fluorinated amine compounds is demanded, especially in the pharmaceutical sector. Herein, we demonstrate that the controllable double nucleophilic functionalization of an activated alkene synthon, originated from a trifluoropropenyliodonium salt with two distinct nucleophiles, enables the selective synthesis of trifluoromethylated ethylene amines and diamines on broad scale with high efficiency under mild reaction conditions. Considering the chemical nature of the reactants, our synthetic approach brings forth an efficient methodology and provides versatile access to highly fluorinated amines.
RESUMO
UNLABELLED: For the profession of teachers and nurses we need well-trained, highly qualified employees with a sense of vocation. AIM: A comparative analysis of motivation in the choice of career among professional nursing students and teacher-students. METHODS: This analysis was done in Hungary among professional nursing students and students participating in teacher training. In this sample 783 students were analysed. RESULTS: In the choice of career of nurses and teachers the primary motivation is of altruistic nature and also the human characteristics of the chosen career. According to genders in the case of female interviewed people we got a higher value than in the case of males in connection with "Helping people". It is more typical in the case of professional nursing students to choose the career as early as in their childhood. Choosing the career at a later age is typical for those who are teacher-students. CONCLUSION: As a consequence of our rapid economic changes or because of career dissatisfaction, we have to face the fact that the qualifications obtained at a young age will not last for a life time, and the majority of people are forced to change their jobs several times during their lives. In harmonizing the demands of the labour market and education, those people who take part in professional education and training have a professional advantage.
Assuntos
Escolha da Profissão , Educação Profissionalizante/tendências , Motivação , Meio Social , Valores Sociais , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Ensino , Adulto , Fatores Etários , Altruísmo , Educação Continuada/tendências , Educação em Enfermagem/tendências , Feminino , Humanos , Hungria , Masculino , Fatores Sexuais , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricosRESUMO
UNLABELLED: According to our knowledge, there has never been a comprehensive research in Hungary dealing with healthcare university or college students' social background. AIM: The main objectives of our cross-section research were to analyze differences in the social background of female students who decided to become doctors, professional nurses and health visitors. METHOD: This research was conducted among female medical and nursing college students at the Semmelweis University. There were 295 students invited to participate, the response rate was 68,08% (N = 201). Data analysis was performed by SPSS software by using descriptive methods of statistics. RESULTS: We found a decisive difference among medical, nursing and health visitor students while analyzing a number of socio-demographic characteristics. Most medical students came from families where the parents had college or university degrees, but we can state that there is a minimal likelihood in the case of college students that they are descendants of parents with higher educational degrees. We did not find statistical differences in the three student sample groups regarding their marital status, but fewer nursing college students lived in marriage or household partnership. CONCLUSION: We found a significant difference in the social background of nursing college and medical students. The social disadvantages of nursing and health visitor students are more considerable than those of medical students.
Assuntos
Pais/educação , Saúde Pública/educação , Classe Social , Estudantes de Medicina/estatística & dados numéricos , Estudantes de Enfermagem/estatística & dados numéricos , Adulto , Estudos Transversais , Escolaridade , Pai/educação , Feminino , Humanos , Hungria , Mães/educação , Razão de Chances , Relações Pais-Filho , Fatores SocioeconômicosRESUMO
BACKGROUND: Most cases of vertigo are attributable to both peripheral and central vestibular disorders. Therefore, it would be of interest to determine whether a combination therapy having both peripheral and central actions would translate into more efficient symptom relief. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of a fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg in the treatment of vertigo of central, peripheral, or combined central/peripheral origin. METHODS: This was a prospective, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group, outpatient study in men and women (age >30 years) with central, peripheral, or combined central/peripheral vestibular vertigo. Patients who assessed > or =1 vertigo symptom as being of medium intensity (> or =2) on a 5-point visual analog scale (from 0 = no symptoms to 4 = very severe symptoms) and who had abnormal vestibulospinal movement patterns on cramocorpography were eligible. Patients were randomly assigned to receive 1 tablet of the fixed combination of cinnarizine 20 mg + dimenhydrinate 40 mg, cinnarizine 50 mg, dimenhydrinate 100 mg, or placebo 3 times daily for 4 weeks. The primary efficacy end point was the decrease in mean vertigo score (MVS), which was composed of 12 individual vertigo symptoms, each assessed on the 5-point visual analog scale after 4 weeks of treatment. RESULTS: The study enrolled 246 patients, of whom 239 were evaluable for efficacy. Approximately two thirds of the efficacy population were female and one third male. The mean age was 51.3 years, and the mean duration of vertigo was 2.6 years. The least squares mean (SD) change from baseline in MVS was significantly greater in the group receiving the fixed combination (1.37 [0.66]) than in any of the comparator groups (cinnarizine 50 mg: 0.87 [0.53]; dimenhydrinate 100 mg: 0.83 [0.66]; placebo: 0.76 [0.48]; all comparisons, P < 0.001). The differences were clinically relevant, based on the Mann-Whitney estimator. The incidence of vertigo-associated nausea was significantly reduced in the fixed-combination group relative to the comparator groups (P< or = 0.016). Thirty-four patients reported adverse events, 6 each in the fixed combination and placebo groups, 12 in the cinnarizine group, and 10 in the dimenhydrinate group. None of these adverse events were considered serious. After 4 weeks of treatment, the tolerability of treatment was rated as very good or good by 57 (96.6%) patients in the fixed-combination group; the values for cinnarizine, dimenhydrinate, and placebo were 54 (93.1%), 42 (72.4%), and 50 (87.7%), respectively. CONCLUSIONS: In this study, the fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg was effective, clinically beneficial, and well tolerated in patients with vestibular vertigo of central and/or peripheral origin. It was significantly more effective in reducing the MVS compared with placebo and the routinely prescribed higher doses of cinnarizine (50 mg) and dimenhydrinate (100 mg).
Assuntos
Cinarizina/uso terapêutico , Dimenidrinato/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Vertigem/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cinarizina/efeitos adversos , Dimenidrinato/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológicoRESUMO
Inappropriate repair of UV-induced DNA damage results in human diseases such as Xeroderma pigmentosum (XP), which is associated with an extremely high risk of skin cancer. A variant form of XP is caused by the absence of Polη, which is normally able to bypass UV-induced DNA lesions in an error-free manner. However, Polη is highly error prone when replicating undamaged DNA and, thus, the regulation of the proper targeting of Polη is crucial for the prevention of mutagenesis and UV-induced cancer formation. Spartan is a novel regulator of the damage tolerance pathway, and its association with Ub-PCNA has a role in Polη targeting; however, our knowledge about its function is only rudimentary. Here, we describe a new biochemical property of purified human SPARTAN by showing that it is a DNA-binding protein. Using a DNA binding mutant, we provide in vivo evidence that DNA binding by SPARTAN regulates the targeting of Polη to damage sites after UV exposure, and this function contributes highly to its DNA-damage tolerance function.
Assuntos
Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , DNA/metabolismo , DNA/efeitos da radiação , Células HEK293 , Humanos , Raios UltravioletaAssuntos
Agamaglobulinemia/cirurgia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndromes de Imunodeficiência/cirurgia , Agamaglobulinemia/genética , Criança , Feminino , Genes Dominantes , Predisposição Genética para Doença , Heterozigoto , Histocompatibilidade , Humanos , Síndromes de Imunodeficiência/genética , Infecções/etiologia , Doadores Vivos , Linhagem , Receptores CXCR4/genética , Indução de Remissão , Irmãos , Síndrome , Verrugas/etiologia , Verrugas/virologiaRESUMO
The evaluation of cochleovestibular dysfunction in psychiatric patients often causes a difficult problem in neurootological experience. The authors discuss here the neurobiological basis of panic disorders and cochleovestibular dysfunction. In this multicenter study, we examined 63 patients with vertigo and panic disease. Twenty patients with primary panic disease and consecutive vertigo composed group 1, whereas group 2 comprised 43 vertiginous patients with secondary panic disease. The most interesting question is whether the patients have an organic vestibular lesion, which would explain why vertigo alone is the problematic symptom in these panic patients, whereas in other patients, panic disease can cause other severe symptoms that resemble heart attack, dyspnea, or abdominal crisis. Vertigo has a bidirectional connection with psychiatric disorders. The panic disorder can be superimposed on chronic vertigo, and psychiatric patients with a cochleovestibular lesion have diminished chances for complete recovery. The examination of psychiatric patients with vertigo is very time consuming and requires much more empathy than does examination of vertiginous patients with a normal mental state. Anxiety provokes somatic and behavioral symptoms in most such patients. The treatment of vertigo in panic patients and of the panic disorder in vertiginous patients requires cooperation between neurootologist and psychiatrist.
Assuntos
Transtorno de Pânico/complicações , Vertigem/complicações , Adulto , Eletronistagmografia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Humanos , Doenças do Labirinto/complicações , Doenças do Labirinto/fisiopatologia , Masculino , Anamnese , Transtornos Mentais/complicações , Transtornos Mentais/fisiopatologia , Transtorno de Pânico/fisiopatologia , Escalas de Graduação Psiquiátrica , Reflexo Vestíbulo-Ocular/fisiologia , Estudos Retrospectivos , Inquéritos e Questionários , Vertigem/fisiopatologia , Testes de Função VestibularRESUMO
Population averaged brain activation studies require the spatial standardization of the individual perfusion PET images. This procedure is usually supported by T1-weighted MRI images. The authors developed a segmentation technique to improve the automatized transformation of the individual MRI images into Talairach space. It was for the first time in Hungary that population averages of standardized T1-weighted MRI and [15O]-butanol PET images of the brain were created after validation of the procedure using data from 23 healthy volunteers. The newly developed method offers a solution for the automatized processing of primary data from brain activation experiments prior to statistical analysis.