RESUMO
Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research.
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Resistência à Insulina , Humanos , Resistência à Insulina/fisiologia , Receptor de Insulina , Glicemia/metabolismo , Hemoglobinas Glicadas , Insulina/farmacologia , Biomarcadores , Modelos TeóricosRESUMO
AIMS: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. MATERIALS AND METHODS: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. RESULTS: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. CONCLUSIONS: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis.
Assuntos
Neuroblastoma , Derrame Pleural , Ascite/etiologia , Ascite/patologia , Biomarcadores Tumorais , Humanos , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/cirurgia , Derrame Pleural/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , África do Sul/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
Osteoporosis is characterised by low bone mineral density (BMD) and is a significant public health problem in India. This cross-sectional study was done to assess the relationship between various anthropometric measures and BMD in 308 rural dwelling South Indian postmenopausal women. Anthropometric variables such as weight, body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured. BMD was assessed by dual-energy X-ray absorptiometry (DXA) scan at the lumbar spine (LS) and femoral neck (NOF). The mean age ± SD of study participants was 60.7 ± 7.8 years. All anthropometric variables showed positive correlation with BMD at NOF and LS (P < 0.05). Weight showed the best correlation (r = 0.482 for NOF and 0.412 for LS; P < 0.001). On multivariate logistic regression, age and weight remained significant for predicting femoral neck osteoporosis while weight and WC were the best predictors for LS osteoporosis. These anthropometric measures may serve as surrogate markers for osteoporosis and thus be used to screen postmenopausal women for referral to a centre with fewer limited resources.
Assuntos
Assistência Ambulatorial/métodos , Osteoporose Pós-Menopausa/diagnóstico , Absorciometria de Fóton , Idoso , Antropometria , Pesos e Medidas Corporais , Densidade Óssea/fisiologia , Estudos Transversais , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiopatologia , Humanos , Índia/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Fatores de Risco , População RuralRESUMO
AIM: To validate bioimpedance based predictive equations for fat free mass (FFM) against DEXA and to derive a novel birth weight based predictive equation for FFM in a birth weight based cohort of healthy Asian Indian men. METHODOLOGY: Whole body composition was done using DEXA and bioimpedance in 117 young Asian Indian men, born of normal birth weight (nâ¯=â¯59, birth weight ≥2.5â¯kg) or low birth weight (nâ¯=â¯58, birth weightâ¯<â¯2.5â¯kg). Predictive accuracy of 11 different bioimpedance based equations for FFM was evaluated using Pearson's correlation analysis and the root of mean squared prediction error (RMSE) analysis. RESULTS: The mean FFM (on DEXA) and total lean mass & impedance index (on bioimpedance) were significantly higher in the low birth weight cohort. Significantly higher body fat percentage was noted on bioimpedance, for the normal birth weight cohort, but not on DEXA. In addition, the mean values of predicted FFM were significantly higher in the low birth weight cohort for 9 different predictive equations. Specifically, the mean FFM values obtained using the predictive equations of Schaefer et al., Hoot cooper et al. and Hughes et al. were in close agreement with the actual FFM values on DEXA. A novel predictive equation (CMC equation) for FFM based on birth weight was derived. FFM = 32.637 + (-0.222*age) + (-32.51*waist-to-hip ratio) + (0.33*body mass index) + (1.58 * 1 or 2 (1 = normal birth weight, 2 = low birth weight) + (0.510*waist circumference). CONCLUSIONS: Our study findings substantiate the validity of Bio-impedance analysis (BIA) as a reliable and noninvasive tool for estimating body composition measures in birth-weight based cohorts of Asian Indian males. Further, we have devised a novel BIA-based predictive equation that can be useful in larger epidemiological studies to look at alterations in body fat in this cohort.
Assuntos
Composição Corporal , Impedância Elétrica , Tecido Adiposo , Adolescente , Adulto , Peso ao Nascer , Estudos de Coortes , Estudos Transversais , Humanos , Índia , MasculinoRESUMO
AIMS: To describe the baseline characteristics of participants in the Kerala Diabetes Prevention Program. METHODS: The Kerala Diabetes Prevention Program is a cluster randomized controlled trial of lifestyle intervention for prevention of Type 2 diabetes mellitus in India. Participants in the study were those aged 30-60 years who had an Indian Diabetes Risk Score ≥ 60 and who were without Type 2 diabetes on oral glucose tolerance test. Data on demographic, lifestyle, clinical and biochemical characteristics were collected using standardized tools. RESULTS: A total of 2586 individuals were screened with the Indian Diabetes Risk Score, of these 1529 people (59.1%) had a score ≥ 60, of whom 1209 (79.1%) underwent an oral glucose tolerance test. A total of 202 individuals (16.7%) had undiagnosed Type 2 diabetes and were excluded, and the remaining 1007 individuals were enrolled in the trial (control arm, n = 507; intervention arm, n = 500). The mean participant age was 46.0 ± 7.5 years, and 47.2% were women. The mean Indian Diabetes Risk Score was 67.1 ± 8.4. More than two-thirds (69.0%) had prediabetes and 31.0% had normal glucose tolerance. The prevalence of cardiometabolic risk factors was high, including current tobacco use (34.4% in men), current alcohol use (39.3% in men), no leisure time exercise (98.0%), no daily intake of fruit and vegetables (78.7%), family history of diabetes (47.9%), overweight or obesity (68.5%), hypertension (22.3%) and dyslipidemia (85.4%). CONCLUSIONS: The Kerala Diabetes Prevention Program recruited participants using a diabetes risk score. A large proportion of the participants had prediabetes and there were high rates of cardiometabolic risk factors. The trial will evaluate the effectiveness of lifestyle intervention in a population selected on the basis of a diabetes risk score.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Estado Pré-Diabético/terapia , Prevenção Primária/métodos , Comportamento de Redução do Risco , Adulto , Povo Asiático , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Índia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Estado Pré-Diabético/etnologiaRESUMO
Background: Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature.Methods: An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers.Results: The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur.Conclusion: An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism
Assuntos
Biomarcadores , Doença da Artéria Coronariana , Exercício Físico , Fatores de Risco , África do SulRESUMO
Phytoextraction is influenced by the indigenous soil microbial communities during the remediation of heavy metal contaminated soils. Soil microbial communities can affect plant growth, metal availability and the performance of phytoextraction-assisting inocula. Understanding the basic ecology of indigenous soil communities associated with the phytoextraction process, including the interplay between selective pressures upon the communities, is an important step towards phytoextraction optimization. This study investigated the impact of cadmium (Cd), and the presence of a Cd-accumulating plant, Carpobrotus rossii (Haw.) Schwantes, on the structure of soil-bacterial and fungal communities using automated ribosomal intergenic spacer analysis (ARISA) and quantitative PCR (qPCR). Whilst Cd had no detectable influence upon fungal communities, bacterial communities underwent significant structural changes with no reduction in 16S rRNA copy number. The presence of C. rossii influenced the structure of all communities and increased ITS copy number. Suites of operational taxonomic units (OTUs) changed in abundance in response to either Cd or C. rossii, however we found little evidence to suggest that the two selective pressures were acting synergistically. The Cd-induced turnover in bacterial OTUs suggests that Cd alters competition dynamics within the community. Further work to understand how competition is altered could provide a deeper understanding of the microbiome-plant-environment and aid phytoextraction optimization.
Assuntos
Aizoaceae/efeitos dos fármacos , Biodegradação Ambiental/efeitos dos fármacos , RNA Ribossômico 16S/genética , Microbiologia do Solo , Aizoaceae/classificação , Aizoaceae/genética , Bactérias/genética , Cádmio/toxicidade , Fungos/genética , Metais Pesados/toxicidade , Microbiota/efeitos dos fármacos , Microbiota/genética , Raízes de Plantas/microbiologia , RizosferaRESUMO
In the nervous system, axons transmit information in the form of electrical impulses over long distances. The speed of impulse conduction is enhanced by myelin, a lipid-rich membrane that wraps around axons. Myelin also is required for the long-term health of axons by providing metabolic support. Accordingly, myelin deficiencies are implicated in a wide range of neurodevelopmental and neuropsychiatric disorders, intellectual disabilities, and neurodegenerative conditions. Central nervous system myelin is formed by glial cells called oligodendrocytes. During development, oligodendrocyte precursor cells migrate from their origins to their target axons, extend long membrane processes that wrap axons, and produce the proteins and lipids that provide myelin membrane with its unique characteristics. Myelination is a dynamic process that involves intricate interactions between multiple cell types. Therefore, an in vivo myelination model, such as the zebrafish, which allows for live observation of cell dynamics and cell-to-cell interactions, is well suited for investigating oligodendrocyte development. Zebrafish offer several advantages to investigating myelination, including the use of transgenic reporter lines, live imaging, forward genetic screens, chemical screens, and reverse genetic approaches. This chapter will describe how these tools and approaches have provided new insights into the regulatory mechanisms that guide myelination.
Assuntos
Diferenciação Celular/genética , Análise Citogenética/métodos , Neurogênese/genética , Oligodendroglia/citologia , Animais , Animais Geneticamente Modificados , Axônios/metabolismo , Comunicação Celular/genética , Embrião não Mamífero , Bainha de Mielina/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
When soluble metal salts are placed in a silicate solution, chemical gardens grow. These gardens are treelike structures formed of long, thin, hollow tubes. Here we study one particular case: a calcium nitrate pellet in a solution of sodium trisilicate. We observe that tube growth results from a relaxation oscillation. The average period and the average growth rate are approximately constant for most of the structures growth. The period does fluctuate from cycle to cycle, with the oscillation amplitude proportional to the period. Based on our observations, we develop a model of the relaxation oscillations which calculates the average oscillation period and the average tube radius in terms of fundamental membrane parameters. We also propose a model for the average tube growth rate. Predictions are made for future experiments.
RESUMO
Angiostatin, a 38 kDa fragment of plasminogen, potently inhibits the growth of blood vessels. Angiostatin is generated from plasminogen by urokinase-type (uPA) and tissue-type (tPA) plasminogen activators in the presence of free sulphydryl donors. Angiogenesis inhibitors may be important in regulating angiogenesis in developing goitre. We have examined angiostatin formation in human primary thyrocyte cultures and a rat thyrocyte cell line (FRTL-5). We found that human thyroid cells in culture secrete plasminogen activators (both tPA and uPA) as well as matrix metalloproteinase 2 into the medium. When human thyrocyte conditioned medium was incubated with plasminogen (10 microg/ml) and N-acetylcysteine (100 microM) for 24 h, a 38 kDa fragment of plasminogen, which is consistent with angiostatin, was generated. The appearance of the 38 kDa fragment was increased by agents that increase cAMP (forskolin and 8 BrcAMP). FRTL-5 cells, which do not secrete uPA or tPA, did not generate angiostatin. Thyroid cells produce several angiogenic growth factors, and human thyrocyte conditioned medium stimulated growth of endothelial cells. When the conditioned medium was incubated with plasminogen and N-acetylcysteine, this stimulatory effect was lost, consistent with the production of a growth inhibitory factor. We conclude that thyroid cells can produce angiostatin from plasminogen in vitro, and this may play a role in vivo in limiting goitre size.
Assuntos
Bócio/patologia , Fragmentos de Peptídeos/metabolismo , Ativadores de Plasminogênio/metabolismo , Plasminogênio/metabolismo , Glândula Tireoide/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Acetilcisteína/farmacologia , Análise de Variância , Angiostatinas , Animais , Linhagem Celular , Células Cultivadas , Colforsina/farmacologia , Meios de Cultivo Condicionados , AMP Cíclico/metabolismo , Bócio/metabolismo , Bócio/fisiopatologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Plasminogênio/farmacologia , Ratos , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
OBJECTIVE: To determine the potential for asphalt fume exposure to increase DNA damage, we conducted a cross-sectional study of roofers involved in the application of roofing asphalt. METHODS: DNA strand breaks and the ratio of 8-hydroxydeoxyguanosine (8-OHdG) to 2-deoxyguanosine (dG) were measured in peripheral blood leukocytes of roofers. In addition, urinary excretion of 8-OHdG and 8-epi-prostaglandin F2alpha (8-epi-PGF) was also measured. The study population consisted of 26 roofers exposed to roofing asphalt and 15 construction workers not exposed to asphalt during the past 5 years. A subset of asphalt roofers (n = 19) was exposed to coal-tar pitch dust (coal tar) during removal of existing roofs prior to applying hot asphalt. Personal air monitoring was performed for one work-week to measure exposure to total particulates, benzene-soluble fraction of total particulates, and polycyclic aromatic compounds (PACs). Urinary 1-OH-pyrene levels were measured as an internal biomarker of PAC exposure. RESULTS: Full-shift breathing zone measurements for total particulates, benzene-solubles and PACs were significantly higher for coal-tar exposed workers than for roofers not exposed to coal tar. Similarly, urinary 1-OH-pyrene levels were higher in coal-tar exposed roofers than roofers not exposed to coal tar. Total particulates or benzene-soluble fractions were not associated with urinary 1-OH-pyrene, but PAC exposure was highly correlated with urinary 1-OH-pyrene. When stratified by 1-OH-pyrene excretion, DNA strand breaks increased in a dose-dependent manner, and leukocyte 8-OHdG/dG decreased in a dose-dependent manner. Significant changes in DNA damage appeared to be linked to PACs from coal-tar exposure, although asphalt fume alone was associated with a small but significant increase in urinary 1-OH-pyrene and DNA strand breaks. CONCLUSIONS: Results are consistent with previous reports that asphalt or coal-tar exposure can cause DNA damage. Urinary 8-epi-PGF remained relatively constant during the week for virtually all subjects, regardless of exposure indicating that neither asphalt nor coal-tar exposure induces an overt oxidative stress. A small, but statistically significant increase in 8OHdG was evident in end-of-week urine samples compared with start-of-week urine samples in roofers exposed to coal-tar. The increase in urinary 8OHdG coupled with the decrease in leukocyte 8-OHdG/dG, suggests that coal-tar exposure induces protective or repair mechanisms that result in reduced levels of steady-state oxidative-DNA damage.
Assuntos
Materiais de Construção/efeitos adversos , Dano ao DNA , Desoxiguanosina/análogos & derivados , Hidrocarbonetos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Pirenos/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Desoxiguanosina/sangue , Desoxiguanosina/urina , Dinoprosta/urina , Poeira , Humanos , Leucócitos/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo , Fumar , Estados UnidosRESUMO
BACKGROUND: Trigeminal neuralgia (TN) is the most common cephalic neuralgia in people over the age of fifty, with a mean incidence of 4 per 100,000. Percutaneous stereotactic differential radiofrequency thermal rhizotomy (RTR) is a well-recognized surgical treatment for TN. The purpose of this study was to evaluate a management algorithm for TN and to evaluate the effectiveness of RTR for TN after failure of pharmacologic management. METHODS: Two hundred and fifty-eight (258) patients underwent RTR from 1992-1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring re-operation, and the type and rate of complications. They were followed by serial clinical evaluation and telephone interview. Patients were grouped according to results: (A) Successful Result--excellent or good pain relief; (B) Unsuccessful Result--fair, poor or no pain relief. The RTR group was compared to historical controls. Follow-up ranged from 12-80 months (mean = 38 months). RESULTS: At early follow-up (defined as median postoperative period up to 6 months), pain relief that was excellent or good (successful results) occurred in 224/258 (87%). At long-term follow-up (> 6 months) recurrence of tic pain required re-operation in 31 patients (12%). In 37 patients (14%), recurrence of tic pain did not require re-operation. Dysesthesia developed in 20 patients (8%); corneal analgesia developed in 8 patients (3%). "Anesthesia dolorosa" developed in 5 patients (2%) and was medically managed. At the conclusion of the long-term follow-up period, 214/258 patients (83%) had excellent to good pain relief (successful result). There were no mortalities, no significant morbidity and a low rate of minor complications. CONCLUSION: With the use of this specific diagnostic and management algorithm, patients with TN can be successfully managed with RTR.
Assuntos
Radiocirurgia , Rizotomia/métodos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiocirurgia/métodosRESUMO
Calcium signaling is known to be important for regulating the guidance of migrating neurons, yet the molecular mechanisms underlying this process are not well understood. We have found that two different voltage-gated calcium channels are important for the accurate guidance of postembryonic neuronal migrations in the nematode Caenorhabditis elegans. In mutants carrying loss-of-function alleles of the calcium channel gene unc-2, the touch receptor neuron AVM and the interneuron SDQR often migrated inappropriately, leading to misplacement of their cell bodies. However, the AVM neurons in unc-2 mutant animals extended axons in a wild-type pattern, suggesting that the UNC-2 calcium channel specifically directs migration of the neuronal cell body and is not required for axonal pathfinding. In contrast, mutations in egl-19, which affect a different voltage-gated calcium channel, affected the migration of the AVM and SDQR bodies, as well as the guidance of the AVM axon. Thus, cell migration and axonal pathfinding in the AVM neurons appear to involve distinct calcium channel subtypes. Mutants defective in the unc-43/CaM kinase gene showed a defect in SDQR and AVM positioning that resembled that of unc-2 mutants; thus, CaM kinase may function as an effector of the UNC-2-mediated calcium influx in guiding cell migration.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/citologia , Canais de Cálcio/fisiologia , Movimento Celular/fisiologia , Proteínas de Membrana , Neurônios/citologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Caenorhabditis elegans/genética , Canais de Cálcio/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/fisiologia , Movimento Celular/genética , Primers do DNA , Proteínas de Helminto/genética , Ativação do Canal Iônico , Dados de Sequência Molecular , MutaçãoRESUMO
BACKGROUND: The present review summarizes the cellular action of TGF-beta in benign and malignant growth of the prostate. METHODS: TGF-beta is a pleiotropic growth factor. It plays an important role in the regulation of growth and differentiation in many cells. In benign prostatic epithelia, its action is mediated through a paracrine mechanism. It inhibits proliferation and induces apoptosis in prostatic epithelia. It provides a mechanism to maintain epithelial homeostasis in the prostate. In prostatic stroma, its continual action leads to smooth muscle differentiation. This effect of TGF-beta may regulate the development of prostatic smooth muscle nodules in benign prostatic hyperplasia. RESULTS: As prostatic epithelial cells undergo malignant transformation, two major events occur regarding TGF-beta action. These include the loss of expression of functional TGF-beta receptors and overproduction of TGF-beta in malignant cells. The loss of expression of functional TGF-beta receptors provides a growth advantage to cancer cells over their benign counterparts. The overproduction of TGF-beta by cancer cells has a multitude of adverse consequences. TGF-beta can promote extracellular matrix production, induce angiogenesis, and inhibit host immune function. The biological consequence of these activities is an enhanced tumorigenicity in prostate cancer. Results of our recent studies with a rat prostate cancer model suggest that the immunosuppressive effect of TGF-beta seems to be the primary cause of tumor progression. This is because, if these cancer cells were engineered to reduce the production of TGF-beta, tumor growth was inhibited in syngeneic hosts but not in immune compromised hosts. CONCLUSIONS: Our future research should take advantage of this knowledge to devise therapeutic strategies aimed at eradicating prostate cancer.
Assuntos
Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Androgênios/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Regulação para CimaRESUMO
P-type and Q-type calcium channels mediate neurotransmitter release at many synapses in the mammalian nervous system. The alpha 1A calcium channel has been implicated in the etiologies of conditions such as episodic ataxia, epilepsy and familial migraine, and shares several properties with native P- and Q-type channels. However, the exact relationship between alpha 1A and P- and Q-type channels is unknown. Here we report that alternative splicing of the alpha 1A subunit gene results in channels with distinct kinetic, pharmacological and modulatory properties. Overall, the results indicate that alternative splicing of the alpha 1A gene generates P-type and Q-type channels as well as multiple phenotypic variants.
Assuntos
Processamento Alternativo , Canais de Cálcio/fisiologia , Variação Genética , Fragmentos de Peptídeos/genética , Sequência de Aminoácidos , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Proteínas de Ligação ao GTP/fisiologia , Regulação da Expressão Gênica/fisiologia , Ativação do Canal Iônico , Dados de Sequência Molecular , Fenótipo , Isoformas de Proteínas/genética , Proteína Quinase C/fisiologia , Células de Purkinje/fisiologia , Ratos , Venenos de Aranha/farmacologia , Xenopus , ômega-Agatoxina IVARESUMO
PURPOSE: The purpose of this study was to evaluate the effectiveness of radiofrequency thermal rhizotomy (RTR) for trigeminal neuralgia, after failure of pharmacological management. PATIENTS AND METHODS: Two hundred fifteen patients underwent RTR from 1991 to 1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face, and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring reoperation, and the type and rate of complications. They were followed-up by serial clinical evaluation and telephone interview. Patients were categorized into groups: 1) Successful result: excellent, good pain relief; and 2) Unsuccessful result: fair, poor, or no pain relief. The RTR group was compared with historical controls. Follow-up ranged from 9 to 68 months (mean, 32 months) and results were evaluated at early and long-term follow-up. RESULTS: At early follow-up (defined as immediately postoperatively to 6 months), pain relief of excellent or good quality (successful result) occurred in 198 of 215 patients (92%). Fair or poor or no pain relief (unsuccessful result) occurred in 17 (8%) patients. At long-term follow-up (>6 months to 68 months), recurrence of pain that required reoperation occurred in 24 patients (11%) and recurrence of pain that did not require reoperation (medically managed) occurred in 34 patients (16%). Dysesthesia developed in 18 patients (8%); seven patients (3%) had dysesthesia alone (medically managed) and 11 patients (5%) had dysesthesia with recurrence of pain (medically or surgically managed). "Anesthesia/analgesia dolorosa" developed in four patients (1.8%) and was medically managed. At long-term follow-up, 83% of patients had good to excellent pain relief (successful result). There were no mortalities, no significant morbidity, and a low rate of minor complications. CONCLUSION: With the use of this specific diagnostic approach and management algorithm, patients with trigeminal neuralgia can be successfully managed.
Assuntos
Radiocirurgia , Rizotomia , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Seguimentos , Humanos , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Recidiva , Reoperação , Rizotomia/efeitos adversos , Transtornos de Sensação/tratamento farmacológico , Transtornos de Sensação/etiologia , Resultado do Tratamento , Neuralgia do Trigêmeo/classificação , Neuralgia do Trigêmeo/tratamento farmacológicoRESUMO
Much new information has become available as interest has grown in issues of biofilm formation and dental unit water quality. This interest is combined with a growing concern for occupational safety and for patients with diminished resistance. A review of recent literature spurred interest amongst the staff of The Hamilton-Wentworth Regional Public Health Department to carry out a quality audit of the dental unit water quality in clinics operated by the Department's Dental Services. Water testing was carried out, and problems with biofilm formation and water quality were identified. An interdisciplinary consultation process helped identify problems, offered possible solutions and made decisions on appropriate action to be taken. Some conservative interventions were successfully implemented even while it was recognized that more involved interventions were also needed. Repeat testing was carried out until the water quality in the clinical waterlines reached acceptable levels. Biofilm management to ensure water quality for both patients and staff, is now an integral part of quality management in the Hamilton-Wentworth Regional Dental Clinics.
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Equipamentos Odontológicos/microbiologia , Controle de Infecções Dentárias , Microbiologia da Água , Biofilmes , Clínicas Odontológicas , Contaminação de Equipamentos/prevenção & controle , HumanosRESUMO
BACKGROUND AND OBJECTIVE: Intravascular ultrasound (IVUS) has been used successfully to detect intravascular lesions. This study evaluates the ability of IVUS to detect acoustic damage to the arterial wall following high power, pulsed laser ablation. STUDY DESIGN/MATERIALS AND METHODS: Arterial ablation and disruption were performed in necropsy bovine aorta with a Ho:YAG laser using energy ranging from 140-720 mJ/pulse at 5 Hz. Laser energy was delivered with 2 mm diameter, multifiber over-the-wire catheters. A 20-MHz IVUS catheter was used to image the arterial damage prior to tissue fixation and morphometry. RESULTS: IVUS images revealed ablation craters surrounded by high acoustically backscattering zones. By histology, the arteries revealed ablation craters lined with thermal coagulation surrounded by a region of dissection and vacuolization. The depth and width of the highly backscattering zones on IVUS images correlated strongly with the corresponding morphometric measurements of tissue dissection (r = 0.92, P = 0.0001 and r = 0.80, P = 0.0001, respectively). Morphometric measurements of the ablation crater depth correlated strongly with laser energy (r = 0.90, P = 0.0001), whereas crater width was not correlated with laser energy (r = 0.27, P = 0.09). CONCLUSION: This study demonstrates that IVUS can detect and measure the extent of arterial damage following pulsed laser ablation. This may provide a means of detecting the extent of tissue disruption and help develop approaches to reduce or prevent extensive tissue damage.