RESUMO
The aim of this work was to investigate associations between individual cow Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity, 305-d corrected milk production, and somatic cell count during 5 lactations lifespan in Portuguese dairy herds using multilevel mixed models. We used MAP serum ELISA (Idexx MAP Ac, Idexx Laboratories Inc., Westbrook, ME) results (n = 23,960) from all the 20,221 adult cows present in 329 farms and corresponding 47,586 lactation records from the National Dairy Improvement Association. Cows and farms were classified as positive or negative. Multilevel mixed models were used to investigate the association of cow MAP status with variation in milk production and somatic cell count. Cow MAP status, farm status, and lactation number were considered as independent variables. A quadratic function of lactation number was used to mimic the effect of lactation order on milk production. The models considered 3 levels: measurement occasion (level 1) within cow (level 2) and cow within farm (level 3). Four final models were produced, including all herds and cows, to address the effect of farm status (models 1 and 2) or the effect of cow status (models 3 and 4) on the outcome variables. Our results show that MAP status affects milk production. Losses are detectable from third lactation onward. During the first 5 lactations, positive cows accumulated an average loss of 1,284.8 kg of milk when compared with the negative cows. We also observed that somatic cell counts were higher in positive cows and a positive interaction occurs between cow status and lactation number, suggesting a positive association between MAP infection and increased somatic cell counts. Our results are in line with previous studies, suggesting a possible positive relation between cow milk production and susceptibility to MAP infection.
Assuntos
Doenças dos Bovinos/fisiopatologia , Bovinos , Contagem de Células/veterinária , Lactação/fisiologia , Paratuberculose/fisiopatologia , Animais , Doenças dos Bovinos/microbiologia , Feminino , Leite , Paratuberculose/epidemiologiaRESUMO
INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is frequently associated to other morbid conditions that act as risk factors influencing OSAS morbidity and mortality. AIM: To analyse the presence of co-morbidities in OSAS patients, recruited from a sleep outpatient clinic in Northern Portugal, stratified as a function of OSAS severity. PATIENTS AND METHODS: A cohort of 319 sleep-disordered patients was assessed by clinical and sleep video-polygraphic recording. Patients (n = 209) with sleep respiratory distress had OSAS (n = 145) and severity defined according to Apnoea/Hypopnea Index (AHI); 64 had primary snoring or respiratory distress with AHI < 5; and 110 had other sleep disorders. A full individual background study was possible in 128 OSAS patients. The association to unique or multiple co-morbidities was assessed by clinical and analytical studies in general group or as a function of OSAS severity. RESULTS: The presence of co-morbidities was of 75% in all OSAS patients and of 79.5% in the severe group of OSAS. Forty seven of patients had only one co-morbidity. The most common was obesity (56.3%) followed by high blood pressure, diabetes and other cardiovascular disorders. Obesity was present in 84% among the most severe OSAS cases and always present in those with multiple co-morbidities. When compared with the group of patients without sleep respiratory distress the co-morbidity condition was more frequently related to OSAS (p = 0.0196). CONCLUSION: Comorbidities are commonly associated to OSAS independently of disease severity. Among the comorbidities present obesity was the most common in the most severe OSAS cases.
TITLE: Comorbilidades y gravedad de la apnea del sueño. Estudio en una cohorte de pacientes portugueses.Introduccion. El sindrome de apnea obstructiva del sueño (SAOS) se asocia frecuentemente a otras enfermedades que actuan como factores de riesgo que influyen en la morbilidad y mortalidad del SAOS. Objetivos. Analizar la presencia de comorbilidades en pacientes con SAOS, seleccionados en una clinica del sueño ambulatoria en el norte de Portugal y clasificados atendiendo a la gravedad del SAOS. Pacientes y metodos. Una cohorte de 319 pacientes con trastornos del sueño fueron evaluados mediante estudios clinicos y registro videopoligrafico durante el sueño. Del total de pacientes (n = 209) con distres respiratorio durante el sueño, 145 tenian SAOS con gravedad definida segun el indice de apnea/hipopnea (IAH); 64 presentaban ronquidos primarios o distres respiratorio con IAH < 5; y 110 tenian otros trastornos del sueño. Resultados. La presencia de comorbilidades fue del 75% en todos los pacientes con SAOS y del 79,5% en el grupo de pacientes con SAOS grave; 47 pacientes presentaban una unica comorbilidad, la mas comun de las cuales fue la obesidad (56,3%), seguida de hipertension, diabetes y otros trastornos cardiovasculares. La obesidad estuvo presente en el 84% de los casos mas graves de SAOS y en el 100% de casos con multiples comorbilidades. En comparacion con el grupo de pacientes con distres respiratorio durante el sueño, la comorbilidad aparece normalmente relacionada con el SAOS (p = 0,0196). Conclusion. Las comorbilidades se asocian con frecuencia al SAOS, independientemente de la gravedad de la enfermedad. Entre las comorbilidades presentes, la obesidad resulto ser la mas comun en los casos mas graves de SAOS.
Assuntos
Comorbidade , Síndromes da Apneia do Sono/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Estudos de Coortes , Humanos , Portugal/epidemiologiaRESUMO
The importance of osteoclast-mediated bone resorption in the process of osseointegration has not been widely considered. In this study, cell culture was used to investigate the hypothesis that the function of implant-adherent bone marrow stromal cells (BMSCs) in osteoclastogenesis is influenced by surface topography. BMSCs isolated from femur and tibia of Sprague-Dawley rats were seeded onto 3 types of titanium surfaces (smooth, micro, and nano) and a control surface (tissue culture plastic) with or without osteogenic supplements. After 3 to 14 d, conditioned medium (CM) was collected. Subsequently, rat bone marrow-derived macrophages (BMMs) were cultured in media supplemented with soluble receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as well as BMSC CM from each of the 4 surfaces. Gene expression levels of soluble RANKL, osteoprotegerin, tumor necrosis factor α, and M-CSF in cultured BMSCs at different time points were measured by real-time polymerase chain reaction. The number of differentiated osteoclastic cells was determined after tartrate-resistant acid phosphatase staining. Analysis of variance and t test were used for statistical analysis. The expression of prominent osteoclast-promoting factors tumor necrosis factor α and M-CSF was increased by BMSCs cultured on both micro- and nanoscale titanium topographies (P < 0.01). BMSC CM contained a heat-labile factor that increased BMMs osteoclastogenesis. CM from both micro- and nanoscale surface-adherent BMSCs increased the osteoclast number (P < 0.01). Difference in surface topography altered BMSC phenotype and influenced BMM osteoclastogenesis. Local signaling by implant-adherent cells at the implant-bone interface may indirectly control osteoclastogenesis and bone accrual around endosseous implants.
Assuntos
Materiais Dentários/química , Células-Tronco Mesenquimais/fisiologia , Osteoclastos/fisiologia , Titânio/química , Fosfatase Ácida/análise , Animais , Interface Osso-Implante/patologia , Adesão Celular/fisiologia , Contagem de Células , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Células Cultivadas , Meios de Cultivo Condicionados , Implantes Dentários , Isoenzimas/análise , Fator Estimulador de Colônias de Macrófagos/análise , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Teste de Materiais , Nanoestruturas/química , Osteogênese/fisiologia , Osteoprotegerina/análise , Plásticos/química , Ligante RANK/análise , Ligante RANK/farmacologia , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Fosfatase Ácida Resistente a Tartarato , Fator de Necrose Tumoral alfa/análiseRESUMO
SUMMARY: Age modifies the effect of area-level socioeconomic status (SES) in the risk of fragility hip fractures (HF). For older individuals, the risk of HF increases as SES increases. For younger individuals, risk of HF increases as SES decreases. Our study may help decision-makers to better direct the implementation of political decisions. INTRODUCTION: The effect of socioeconomic status (SES) on hip fracture (HF) incidence remains unclear. The objective of this study is to evaluate the association between HF incidence and municipality-level SES as well as interactions between age and SES. METHODS: From the Portuguese Hospital Discharge Database, we selected hospitalizations (2000-2010) of patients aged 50+, with HF diagnosis (codes 820.x, ICD9-CM), caused by traumas of low/moderate energy, excluding bone cancer cases and readmissions for aftercare. Municipalities were classified according to SES (deprived to affluent) using 2001 Census data. A spatial Bayesian hierarchical regression model (controlling for data heterogeneity and spatial autocorrelation), using the Poisson distribution, was used to quantify the relative risk (RR) of HF, 95% credible interval (95%CrI), and analyze the interaction between age and SES after adjusting for rural conditions. RESULTS: There were 96,905 HF, 77.3% of which were on women who, on average, were older than men (mean age 81.2±8.5 vs 78.2±10.1 years) at admission (p<0.001). In women, there was a lower risk associated with better SES: RR=0.83 (95%CrI 0.65-1.00) for affluent versus deprived. There was an inverse association between SES and HF incidence rate in the youngest and a direct association in the oldest, for both sexes, but significant only between deprived and affluent in older ages (≥75 years). CONCLUSIONS: Interaction between SES and age may be due to inequalities in lifestyles, access to health systems, and preventive actions. These results may help decision-makers to better understand the epidemiology of hip fractures and to better direct the available funding.
Assuntos
Fraturas do Quadril/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Características de Residência , Fatores de Risco , Classe SocialRESUMO
BACKGROUND: Psoriasis is a chronic, immune-mediated disease associated with several cardio-metabolic comorbidities, accelerated atherosclerosis and cardiovascular disease (CVD). Other causes beyond systemic inflammation and traditional cardiovascular risk factors (CVRF) may be implicated in the increased risk of CVD observed in these patients. Epicardial adipose tissue (EAT), a type of visceral adipose tissue surrounding the heart and coronary vessels has been implicated in the development of coronary artery disease, by endocrine mechanisms, but particularly by local inflammation. OBJECTIVE: To compare EAT volumes in psoriasis patients and controls using multidetector computed tomography (MDCT) and to analyse if eventual differences were independent from abdominal visceral adiposity; to determine, within psoriasis patients, its relation with subclinical atherosclerosis and other markers of cardiometabolic risk. METHODS: One hundred patients with severe psoriasis, without CVD underwent MDCT, with EAT and abdominal visceral fat (AVF) assessment and coronary artery calcification (CAC) quantification and were compared with 202 control patients. RESULTS: EAT volume was increased in psoriasis patients compared to control subjects, independently from age, sex and AVF, being, on average, 15.2 ± 4.41 mL higher (95% CI: 6.5-26.0, P = 0.001) than in controls. Moreover, psoriasis patients had a statistically significant higher risk of having subclinical atherosclerosis (OR 2.52, 95% CI: 1.23-5.16) than controls, after adjusting for traditional CVRF. Within psoriasis patients EAT volume was associated with subclinical atherosclerosis, independently of age, sex, psoriasis duration, classical CVRF and AVF. CONCLUSION: This study showed that psoriasis was associated with increased EAT volume independently of visceral abdominal fat and with subclinical atherosclerosis. Within psoriasis patients EAT volume was independently associated with CAC. EAT may be another important contributor to the higher cardiovascular risk observed in psoriasis.
Assuntos
Tecido Adiposo/patologia , Calcinose/patologia , Vasos Coronários/patologia , Pericárdio/patologia , Psoríase/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XAssuntos
Tecido Adiposo , Doença da Artéria Coronariana/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Calcificação Vascular/genética , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Homozigoto , Humanos , Masculino , PericárdioRESUMO
An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis (ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti-Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells (PBMC) were cultured with L. braziliensis antigens (Lb-Ag), Toxoplasma gondii antigens (Tg-Ag), concanavalin-A (Con-A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test (MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST (r = 0·61). Lb-Ag induced interferon (IFN)-γ was correlated positively with duration of illness (r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot (ELISPOT)] assay. No association was observed for Tg-Ag or Con-A. Disease duration was correlated negatively with interleukin (IL)-10 production (r = -0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels (r = -0·94) or the IFN-γ : IL-10 ratio (r = -0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses.
Assuntos
Antígenos de Protozoários/imunologia , Interferon gama/biossíntese , Interleucina-10/biossíntese , Leishmaniose Mucocutânea/imunologia , Leishmaniose Mucocutânea/metabolismo , Adulto , Idoso , Citocinas/biossíntese , Feminino , Humanos , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Tardia/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
INTRODUCTION: Diabetes mellitus is a leading cause of chronic renal failure, challenging therapy strategies. Patients with diabetes may benefit from peritoneal dialysis (PD) but higher technique failure is feared. Our purpose was to critically evaluate clinical outcomes of this modality in diabetics, in order to find quality improvement strategies in these risk patients. METHODS: A registry-based study of 432 incident patients, 23% with diabetes, from a university hospital PD program was performed. Traditional methods (Kaplan-Meier, Cox models) and innovative survival analysis, taking competing risks into account, were performed, as well as exploring the trends in cohorts according to the decade of PD start. RESULTS: In spite of the detrimental effect of diabetes in patient survival compared to non-diabetics (77%, 52% vs 86%, 71%, at 2 and 4 years, respectively; p < 0.0001) the hazard ratio (HR) for death decreased in the more contemporary cohort (0.303, 95% confidence interval (CI) 0.150 - 0.614, p < 0.001). It is noteworthy that diabetes was not associated with lower technique survival: 74%, 51% vs 79%, 57%, at 2 and 4 years, respectively (p = not significant (NS)). On multivariate analysis, diabetes was an independent predictor for mortality, but not for technique failure. The hazard ratio (HR) for technique failure also decreased in the more recent cohort (0.566, 95% CI 0.348 - 0.919, p = 0.021). Among reasons for transfer to hemodialysis, proportion of ultrafiltration failure was similar between groups (26% vs 22%, p = NS), but drop-out due to loss of autonomy occurred more in the group with diabetes (23% vs 5%, p = 0.004), mainly due to ischemic stroke. The hospitalization rate was also higher in diabetic patients (1.39 vs 0.84 episodes per patient-year (E/PY), p = 0.004) but the peritonitis rate was not increased (0.53 vs 0.61 E/PY, p = NS). CONCLUSION: PD was an effective long-term renal replacement therapy in diabetics, without higher rates of technique failure, ultrafiltration failure or peritonitis. Better outcomes were achieved in the contemporary cohort. The menace of autonomy loss due to stroke and higher hospitalization rates enhance the need for assisted PD strategies and better control of comorbidities.
Assuntos
Nefropatias Diabéticas/terapia , Hemodiálise no Domicílio/mortalidade , Hemodiálise no Domicílio/métodos , Falência Renal Crônica/terapia , Diálise Peritoneal/mortalidade , Diálise Peritoneal/métodos , Adulto , Idoso , Causas de Morte , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Seguimentos , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Autonomia Pessoal , Portugal , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Salmonella is the second most frequent cause of foodborne illness in the European Union (EU), so EU enforced legislation to achieve a reduction in Salmonella prevalence in the swine sector. To set the reduction target each country carried out a baseline survey to estimate Salmonella prevalence. The aim of our study was to identify risk factors for the presence of Salmonella in breeding pigs based on the data of the Baseline Study for Salmonella in Breeding Pigs in Portugal. In total, 1670 pen fecal samples from 167 herds were tested by culture and 170 samples tested positive. Along with the collection of the samples a survey was applied to collect information about the herd management and potential risk factors. Multilevel analysis was applied to the data using generalized linear mixed models and a logit link function. The outcome variable was the presence/absence of Salmonella in the pen fecal samples. The first level was assigned to the pen fecal samples and the second level to the herds. The results showed significant associations between Salmonella occurrence and the factors (p<0.05): maternity pens versus mating pens (OR=0.39, 95%CI: 0.24-0.63), feed from external or mixed source versus home source (OR=2.81, 95%CI: 1.19-6.61), more than 10 animals per pen versus 10 animals per pen (OR=2.02, 95%CI: 1.19-3.43), North Region versus Alentejo Region (OR=3.86, 95%CI: 1.08-13.75), rodents control (OR=0.23, 95%CI: 0.090-0.59), more than 90% of boars homebred or no boars versus more than 90% of boars from an external source (OR=0.54, 95%CI: 0.3-0.97), semen from another herd versus semen from insemination centers (OR=4.47, 95%CI: 1.38-14.43) and herds with a size of 170 or more sows (OR=1.82, 95%CI: 1.04-3.19). This study offers very relevant information for both the Portuguese veterinary authorities and the pig farmers currently developing control programmes for Salmonella. This is the first study providing evidence for semen and boars source as risk factors for Salmonella in breeding pigs.
Assuntos
Criação de Animais Domésticos/métodos , Salmonelose Animal/epidemiologia , Salmonella/isolamento & purificação , Doenças dos Suínos/epidemiologia , Animais , Fezes/microbiologia , Feminino , Modelos Logísticos , Análise Multinível , Portugal/epidemiologia , Prevalência , Fatores de Risco , Salmonella/classificação , Salmonelose Animal/microbiologia , Suínos , Doenças dos Suínos/microbiologiaRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown aetiology. Diagnosis is made through physical examination, electrophysiological findings, and by excluding other conditions. There is not a single biomarker that concludes the diagnosis. The aim of this study was to investigate differentially expressed proteins in cerebrospinal fluid (CSF) of ALS patients compared to control subjects, with the purpose to identify a panel of possible biomarkers for the disease. The differentially expressed spots/proteins were submitted to two-dimensional (2D) electrophoresis and recognized with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Parkin-like and many iron and zinc binding were some of the proteins found in ALS CSF. Parkin is a ligase involved in ubiquitin-proteasome pathway and mutations in the parkin gene are the most common cause of recessive familial Parkinson's disease. Iron and zinc are involved with many important metabolic processes and are related to neurodegenerative disease. Common features of ALS comprise failure of the ubiquitin-proteasome system and increased levels of metal ions in the brain. Therefore, the identification of these proteins can be a significant step in ALS research. These and other identified proteins are discussed in this study.
Assuntos
Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Esclerose Lateral Amiotrófica/genética , Proteômica/métodos , Adulto , Idoso , Esclerose Lateral Amiotrófica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica/tendências , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/tendênciasRESUMO
HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics' analyses) recommends avoiding outdated racial classifications and population names (e.g. 'Caucasian') and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. 'pan-European'). A standard 'HLA-NET POPULATION DATA QUESTIONNAIRE' has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in 'HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS'. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the 'gene[rate]' computer tools to estimate frequencies, test for Hardy-Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.
Assuntos
Epidemiologia , Genética Populacional , Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Histocompatibilidade/genética , Transplante , Alelos , Biologia Computacional , Frequência do Gene/genética , Guias como Assunto , Teste de Histocompatibilidade/normas , Humanos , Estatística como AssuntoRESUMO
The myostatin gene (MSTN) belongs to the TGF-ß superfamily of secreted growth and differentiation factors and is responsible for embryonic and adult skeletal muscle development. In this study, exon 2 of the MSTN gene, which encodes part of the TGF-ß pro-peptide, was sequenced in 332 horses of 20 different breeds and compared with the horse MSTN gene sequence deposited in GenBank. The sequences obtained revealed the presence of 11 haplotypes represented by 10 variable nucleotide mutations, eight of them corresponding to amino acid sequence changes. This gene shows a high variability when compared with other genes. This might be an indication that some breeds have the same ancestry but different pressures of selection.
Assuntos
Cavalos/genética , Miostatina/genética , Animais , Éxons , Haplótipos , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Especificidade da EspécieRESUMO
The bark of Xylopia benthamii R.E. Fries was investigated in a search for new bioactive compounds. The ethanolic extract of the air-dried bark of X. benthamii was obtained and submitted to an acidic extraction procedure to obtain an alkaloid mixture. Chromatographic fractionation led to the isolation of two aporphine alkaloids, nornantenine and laurotetanine, and a mixture of trans- and cis-feruloyltyramine, isolated for the first time in this genus. Structures were established by spectroscopic methods as NMR (1D and 2D) and mass spectrometry (ESI-MS).
Assuntos
Alcaloides/química , Aporfinas/química , Casca de Planta/química , Xylopia/químicaRESUMO
The glomus cells in the carotid bodies (CB) detect alterations in pH and pCO2 and low pO2 level in arterial blood. The carotid sinus nerve conveys the information related to the oxygen level to 2nd-order neurons in the nucleus tractus solitarius (NTS) via tractus solitarius (TS), which is part of the chemoreflex pathways. It has been demonstrated that in 2nd-order NTS neurons receiving inputs from the aortic depressor nerve (ADN), the TS stimulation presents high temporal fidelity. However, the temporal properties of synaptic activity in NTS neurons receiving inputs from CB were not yet fully investigated. Herein using patch-clamp recordings in NTS brainstem slices, we studied TS-evoked excitatory postsynaptic currents (TS-eEPSCs) on morphologically identified 2nd-order NTS neurons that receive afferent inputs from the CB and compared with 2nd-order ADN-NTS neurons recorded in the same experimental conditions. The amplitudes of TS-eEPSCs were similar in both groups, but the latencies and standard deviation (SD) of latency were significantly higher in the CB-NTS neurons (latency: 4±0.2 ms, SD: 0.49±0.03 ms) than in ADN-NTS neurons (latency: 3.3±0.3 ms, SD: 0.19±0.02 ms; P=0.049 for latency and P<0.001 for SD of latency). In a series of double-labeling experiments, we confirmed that some CB-NTS 2nd-order neurons send direct projections to the rostral ventrolateral medulla (RVLM). We conclude that: (a) CB-NTS 2nd-order neurons present temporally distinct postsynaptic currents when compared with ADN-NTS 2nd-order neurons; (b) low SD of latency of TS-eEPSCs is not necessarily a characteristic of all 2nd-order neurons in the NTS; and (c) the presence of direct connections between these 2nd-order neurons in the NTS and RVLM is indicative that these synaptic properties of CB-NTS neurons are relevant for the processing of respiratory and autonomic responses to chemoreflex activation.
Assuntos
Vias Neurais/citologia , Vias Neurais/metabolismo , Neurônios/metabolismo , Núcleo Solitário/citologia , Núcleo Solitário/metabolismo , Transmissão Sináptica/fisiologia , Animais , Corpo Carotídeo/metabolismo , Masculino , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
PURPOSE: We performed a retrospective study to examine the impact on long-term graft survival of first-year posttransplantation renal function, as evaluated by serum creatinine. PATIENTS AND METHODS: We analyzed data from 1,273 adult kidney transplants performed between 1983 and 2008. All recipients >18 years old were included if their grafts had survived beyond 1 year, excluding patients simultaneously transplanted with other organs. Cox proportional hazards multivariable analysis was used to examine the relationship between first-year posttransplantation renal function and death-censored graft loss, adjusted for other variables. Renal function in the first year was expressed as serum creatinine levels at 1, 6, and 12 months as well as the change in creatinine between those 3 periods. RESULTS: Posttransplantation 1-month serum creatinine levels and change between 1 and 6 months were independent predictors of long-term graft loss. Multivariable analysis also identified donor age (increasing), acute rejection episode occurrence, recipient age at transplantation (decreasing), and gender (female) as independently predictive of graft failure, adjusting for other factors usually associated with graft loss, namely, pretransplantation time on dialysis, HLA mismatches, and delayed graft function. The predictive effect of creatininemia was sustained at 6 and 12 months, after adjusting for these covariates. CONCLUSIONS: Posttransplantation serum creatinine levels at 1, 6, and 12 months were independent predictors of graft survival, suggesting that they could be considered as surrogate endpoints for long-term death-censored graft loss.
Assuntos
Rejeição de Enxerto , Transplante de Rim , Rim/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Creatinina/sangue , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Not every individual exposed to Mycobacterium tuberculosis becomes infected. One host genetic factor, involved in modulating the immune response that has been studied in many ethnic groups is the association of human leukocyte antigens (HLA) with susceptibility to tuberculosis (TB). OBJECTIVE: To investigate the association between TB, HLA-DRB1 and HLA-DQB1 alleles in a Portuguese population. METHODS: HLA-DRB1 and HLA-DQB1 gene polymorphisms were analyzed by PCR-SSP in 92 TB patients, and 82 healthcare professionals without TB but exposed on a daily basis to infectious patients for more than two years (healthy exposed - HE). Tuberculin skin test reaction (TST), was positive in 69 individuals (all over 15 mm) in the HE group (HE+) and negative in thirteen (HE-). RESULTS: HLA-DRB1*14 frequency is higher in the TB patients group (7 % vs. 0; p = 0.038) than in HE+. CONCLUSIONS: No genetic marker clearly indicative of disease susceptibility or resistance was identified in this study. However, HLA-DRB1*14 was more frequent in TB patients suggesting that it may be involved in the evolution infection towards active TB in our population.
Assuntos
Alelos , Predisposição Genética para Doença , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Imunidade Inata/genética , Polimorfismo Genético , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Marcadores Genéticos/genética , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: High iron concentrations have been reported in oligodendrocytes, myelin and macrophages in multiple sclerosis (MS) lesions. It has been proposed that HFE gene polymorphisms could have a role in MS. METHODS: The C282Y and H63D HFE variants frequencies were determined in 373 patients with MS and compared with a normal population. RESULTS: No significant association was found between HFE polymorphisms and disease susceptibility. An analysis of the association of genotypes with disease severity was performed, and the C282Y allele was more frequent in the aggressive group. CONCLUSIONS: Patients carrying the C282Y variant seem to have a worse prognosis.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Proteína da Hemocromatose , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Portugal , Prognóstico , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Migraine is a common neurological disabling disorder, and anomalies of vascular function have been implied in its pathophysiology. Several findings point to a possible role of the endothelin receptor type A (EDNRA) in migraine. We aim to assess the involvement of endothelin receptor type A (EDNRA) in migraine susceptibility in a sample of Portuguese migraineurs. METHODS: Three tagging SNPs (rs702757, rs5333 and rs5335) were analysed in 188 cases - 111 without aura (MO) and 77 with aura (MA) - and 287 controls. A multivariable logistic regression was performed, including the three SNPs, adjusted for gender. Allelic and haplotypic frequencies were compared between cases and controls. Significant or promising results were confirmed by a multifactor dimensionality reduction analysis (MDR). RESULTS: We found a nominal association for the rs702757 T-allele [odds ratio (OR) = 1.44, 95% confidence intervals (CI): 1.05-1.99] and for the TT-genotype (OR = 2.34, 95% CI: 1.12-4.90) for MO, that do not remain significant after multiple test correction. A trend towards an increased risk for MA regarding the C-allele of rs5333 was also found. However, an additional MDR analysis was performed, and highly significant results were found for the two SNPs. The T-C-G haplotype (rs702757-rs5333-rs5335) was found to be significantly overrepresented in the MO subgroup, even after permutation was performed. CONCLUSIONS: Our results show additional findings for a role of EDNRA as a susceptibility factor for MO, although we cannot exclude the involvement of this gene in MA susceptibility in our population. Our study also emphasizes the need for replication of association findings in different populations.
Assuntos
Predisposição Genética para Doença/genética , Enxaqueca sem Aura/genética , Receptor de Endotelina A/genética , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Portugal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
This study examined the association between demographic [age, sex, socioeconomic status (SES)] and socio-cultural [father, mother, sibling physical activity (PA); peers and physical education teacher influences] correlates and low, moderate and high levels of PA among Portuguese adolescents aged 10-18 years. A total of 3352 males and females attending basic and secondary schools, their parents and siblings were sampled across four regions of Portugal. PA was assessed with a psychometrically validated questionnaire. Multinomial logistic regression was used. Age was positively related with moderate and high PA. Boys and adolescents of high SES were more likely to participate in moderate and high PA. Adolescents were more likely to participate in high PA when theirs mother and sibling(s) also participated. Peers had a positive influence on participation in moderate and high PA, while physical education teachers did not have an influence. The results indicated that demographic and socio-cultural correlates--in particular age, sex, SES, mother and sibling PA, and peer influence--were significantly associated with adolescent PA. These results also suggested that interventions should focus on girls and low SES adolescents who face higher risk of inactivity.