RESUMO
BACKGROUND: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. METHODS: We performed a case-control study of consecutive ischaemic stroke survivors aged ≤45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction-restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. RESULTS: 204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. CONCLUSION: The polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/genética , Estudos de Casos e Controles , Humanos , Fatores de Risco , Acidente Vascular Cerebral/genéticaRESUMO
Background: In chronic hypoxia (CH) and short-term chronic intermittent hypoxia (CIH) exposure, glycemia and insulin levels decrease and insulin sensitivity increases, which can be explained by changes in glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX) and compared the findings. Methods: Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr) group (n = 10), a CIH group (2 days hypoxia/2 days NX; n = 10) and a CH group (n = 10). Rats were exposed to hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m). Feeding (10 g daily) and fasting times were accurately controlled. Measurements included food intake (every 4 days), weight, hematocrit, hemoglobin, glycemia, serum insulin (by ELISA), and insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30. Results: (1) Weight loss and increases in hematocrit and hemoglobin were found in both hypoxic groups (p < 0.05). (2) A moderate decrease in glycemia and plasma insulin was found. (3) Insulin sensitivity was greater in the CIH group (p < 0.05). (4) There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5) The level of activated AMPK was increased only in the CIH group (p < 0.05). (6) Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group (p < 0.05). Conclusion: In lean rats experiencing long-term CIH, glycemia and insulin levels decrease and insulin sensitivity increases. Interestingly, there is no increase of GLUT1 or GLUT4 levels or in Akt activation. Therefore, cellular regulation of glucose seems to primarily involve GLUT4 translocation to the cell membrane in response to hypoxia-mediated AMPK activation.
RESUMO
The use of endogenous protoporphyrin IX after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). We have previously reported that the conjugation of ALA dendrimers enhances porphyrin synthesis. The first aim of this work was to evaluate the ability of ALA dendrimers carrying 6 and 9 ALA residues (6m-ALA and 9m-ALA) to photosensitise cancer cells. For this aim, we employed LM3 mammary carcinoma cells. In these tumour cells, at low concentrations porphyrin synthesis from dendrimers was higher compared to ALA, whereas at high concentrations, porphyrin synthesis was similar from both compounds. Topical application of ALA dendrimers on the skin overlying a subcutaneous LM3 implanted tumour showed no diffusion of the molecules either to distant skin sites or to the adjacent tumour, suggesting a promising use of the ALA macromolecules in superficial cancer models. As a second objective, we proposed the use of ALA-dendrimers in vascular PDT for the treatment of atherosclerosis. Thus, we focused our studies on ALA-dendrimer's selectivity towards macrophages in comparison with endothelial cells. For this aim we employed Raw 264.7 macrophages and HMEC-1 microvasculature cells. Porphyrin synthesis induced in macrophages by 6m-ALA and 9m-ALA (3 h, 0.025 mM) was 6 and 4.6 times higher respectively compared to the endothelial cell line, demonstrating the high affinity of ALA dendrimers for macrophages. On the other hand, ALA employed at low concentrations was slightly selective (1.7-fold) for macrophages. Inhibition studies suggested that ALA dendrimer uptake in macrophages is mainly mediated by caveloae-mediated endocytosis. Our main conclusion is that in addition to being promising molecules in PDT of superficial cancer, ALA dendrimers may also find applications in vascular PDT, since in vitro they showed selectivity to the macrophage component of the atheromatous plaque, as compared to the vascular endothelium.
Assuntos
Adenocarcinoma/tratamento farmacológico , Ácido Aminolevulínico/farmacologia , Dendrímeros/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Ácido Aminolevulínico/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dendrímeros/química , Endocitose/efeitos dos fármacos , Endocitose/fisiologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Neoplasias Mamárias Animais/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Estrutura Molecular , Transplante de Neoplasias , Fármacos Fotossensibilizantes/química , Porfirinas/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
El mesotelioma maligno es una neoplasia originada a partir de las células mesoteliales de las membranas serosas (pleura, peritoneo, pericardio y otros). Es 5 veces más frecuente en la cavidad pleural que en la peritoneal, y puede observarse en ambas por extensión directa a través del diafragma(1). Se presenta el caso de autopsia en una mujer de 83 años, sin antecedentes de exposición al asbesto, oligosintomática, con mesotelioma pleural maligno tipo sarcomatoide, en estadio avanzado (Estadio IV). El mesotelioma es una neoplasia letal, su diagnóstico a veces resulta dificultoso debido al crecimiento lento, las manifestaciones clínicas tardías y el diagnóstico en estadios avanzados. En primer lugar debe descartarse secundarismo y ante clínica e imágenes compatibles debe plantearse su diagnóstico.(AU)
Malignant mesotheliomas are tumors derived from mesothelial cells that form the serous membranes. The incidence of mesotheliomas show a rate 5 times greater in the pleural cavity than in the peritoneum; but they can be detected in both, as a result of direct invasion through the diaphragm. A case out from an autopsy is reported, of a 83 years old female patient, with no previous history of exposure to asbestos, oligosymptomatic, with malignant pleural mesothelioma of sarcomatoideal type, at an advanced stage (Stage IV). Malignant mesotheliomas are relatively rare being a highly lethal neoplasia its diagnosis is sometimes difficult because the have a gradual development and growth, with late clinical manifestions, and with diagnosis at an advanced evolutive stages. First of all, secondarism must be discarged, and in presence of compatibles images, its diagnosis must be hypothesized.(AU)
Assuntos
Idoso de 80 Anos ou mais , Autopsia , Mesotelioma/patologia , Mesotelioma/etiologia , Sinais e Sintomas , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/mortalidade , Tomografia Computadorizada Espiral , Derrame PleuralRESUMO
El mesotelioma maligno es una neoplasia originada a partir de las células mesoteliales de las membranas serosas (pleura, peritoneo, pericardio y otros). Es 5 veces más frecuente en la cavidad pleural que en la peritoneal, y puede observarse en ambas por extensión directa a través del diafragma(1). Se presenta el caso de autopsia en una mujer de 83 años, sin antecedentes de exposición al asbesto, oligosintomática, con mesotelioma pleural maligno tipo sarcomatoide, en estadio avanzado (Estadio IV). El mesotelioma es una neoplasia letal, su diagnóstico a veces resulta dificultoso debido al crecimiento lento, las manifestaciones clínicas tardías y el diagnóstico en estadios avanzados. En primer lugar debe descartarse secundarismo y ante clínica e imágenes compatibles debe plantearse su diagnóstico.
Malignant mesotheliomas are tumors derived from mesothelial cells that form the serous membranes. The incidence of mesotheliomas show a rate 5 times greater in the pleural cavity than in the peritoneum; but they can be detected in both, as a result of direct invasion through the diaphragm. A case out from an autopsy is reported, of a 83 years old female patient, with no previous history of exposure to asbestos, oligosymptomatic, with malignant pleural mesothelioma of sarcomatoideal type, at an advanced stage (Stage IV). Malignant mesotheliomas are relatively rare being a highly lethal neoplasia its diagnosis is sometimes difficult because the have a gradual development and growth, with late clinical manifestions, and with diagnosis at an advanced evolutive stages. First of all, secondarism must be discarged, and in presence of compatibles images, its diagnosis must be hypothesized.
Assuntos
Idoso de 80 Anos ou mais , Autopsia , Mesotelioma/etiologia , Mesotelioma/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/mortalidade , Derrame Pleural , Sinais e Sintomas , Tomografia Computadorizada EspiralRESUMO
BACKGROUND: Parenteral nutrition (PN) is used to control the nutritional state after severe intestinal resections. Whenever possible, enteral nutrition (EN) is used to promote intestinal rehabilitation and reduce PN dependency. Our aim is to verify whether EN + oral intake (OI) in severe short bowel syndrome (SBS) surgical adult patients can maintain adequate nutritional status in the long term. METHODS: This longitudinal retrospective study included 10 patients followed for 7 post-operative years. Body mass index (BMI), percentage of involuntary loss of usual body weight (UWL), free fat mass (FFM), and fat mass (FM) composition assessed by bioelectric impedance, and laboratory tests were evaluated at 6, 12, 24, 36, 48, 60, 72, and 84 months after surgery. Energy and protein offered in HPN and at long term by HEN+ oral intake (OI), was evaluated at the same periods. The statistical model of generalized estimating equations with p < 0,05 was used. RESULTS: With long term EN + OI there was a progressive increase in the UWL, a decrease in BMI, FFM, and FM (p < 0,05). PN weaning was possible in eight patients. Infection due to central venous catheter (CVC) contamination was the most common complication (1.2 episodes CVC/patient/year). There was an increase in energy and protein intake supply provided by HEN+OI (p < 0.05). All patients survived for at least 2 years, seven for 5 years and six for 7 years of follow-up. CONCLUSIONS: In the long term SBS surgical adult patients fed with HEN+OI couldn't maintain adequate nutritional status with loss of FM and FFM.
Assuntos
Avaliação Nutricional , Nutrição Parenteral no Domicílio/métodos , Síndrome do Intestino Curto/terapia , Adolescente , Adulto , Idoso , Composição Corporal , Distribuição da Gordura Corporal , Índice de Massa Corporal , Peso Corporal/fisiologia , Infecções Relacionadas a Cateter/etiologia , Impedância Elétrica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Nutrição Parenteral no Domicílio/efeitos adversos , Estudos Retrospectivos , Síndrome do Intestino Curto/mortalidade , Síndrome do Intestino Curto/fisiopatologia , Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Human bladder cancer has been associated with chronic exposure to arsenic. Chronic exposure of an immortalized non-tumorigenic urothelial cell line (UROtsa cells) to arsenicals has transformed these cells to a malignant phenotype, but the involved mechanisms are not fully understood. Chronic inflammation has been linked with cancer development mainly because many pro-inflammatory cytokines, growth factors as well as angiogenic chemokines have been found in tumors. In this study the chronology of inflammatory cytokines production was profiled in UROtsa cells chronically exposed to the toxic arsenic metabolite, monomethylarsonous acid [50 nM MMA(III)] to know the role of inflammation in cell transformation. Acute 50 nM MMA(III) exposure induced over-production of many pro-inflammatory cytokines as soon as 12 h after acute exposure. The same cytokines remain over-regulated after chronic exposure to 50 nM MMA(III), especially after 3 mo exposure. At 3 mo exposure the sustained production of cytokines like IL-1, IL-6, IL-8 and TNF is coincident with the appearance of characteristics associated with cell transformation seen in other arsenic-UROtsa studies. The sustained and increased activation of NFkappaB and c-Jun is also present along the transformation process and the phosphorylated proteins p38 MAPK and ERK 1/2 are increased also through the time line. Taken together these results support the notion that chronic inflammation is associated within MMA(III)-induced cell transformation and may act as a promoting factor in UROtsa cell transformation.
Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Citocinas/biossíntese , Mediadores da Inflamação/fisiologia , Compostos Organometálicos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Urotélio/efeitos dos fármacos , Linhagem Celular Transformada , Transformação Celular Neoplásica/metabolismo , Citocinas/fisiologia , Humanos , Compostos Organometálicos/toxicidade , Transdução de Sinais/fisiologia , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Urotélio/metabolismo , Urotélio/patologiaRESUMO
This study aimed to compare the resting energy expenditure (REE) of white and non-white severely obese Brazilian women. REE was examined in 83 severely obese Brazilian women (n = 58 white and 25 non-white) with mean (+/- SD) age 42.99 +/- 11.35 and body mass index 46.88 +/- 6.22 kg/m(2) who were candidates for gastric bypass surgery. Body composition was assessed by air displacement plethysmography (ADP) BOD PODO body composition system (Life Measurement Instruments, Concord, CA) and REE was measured, under established protocol, with an open-circuit calorimeter (Deltatrac II MBM-200, Datex-Ohmeda, Madison, WI, USA). There was no significant difference between the REE of white and non-white severely obese women (1,953 +/- 273 and 1,906 +/- 271 kcal/d, respectively; p = 0.48). However, when adjusted for fat free mass (MLG), REE was significantly higher in nonwhite severely obese women (difference between groups of 158.4 kcal, p < 0.01). REE in white women was positively and significantly correlated to C-reactive protein (PCR) (r = 0.418; P < 0.001) and MLG (r = 0.771; P < 0.001). In the non-white women, REE was only significantly correlated to MLG (r = 0.753; P < 0.001). The multiple linear regression analysis showed that skin color, MLG and PCR were the significant determinants of REE (R(2) = 0.55). This study showed that, after adjustment for MLG, non-white severely obese women have a higher REE than the white ones. The association of body composition inflammation factors and REE in severely obese Brazilian women remains to be further investigated.
Assuntos
Metabolismo Basal , Etnicidade/estatística & dados numéricos , Obesidade Mórbida/metabolismo , Adulto , Composição Corporal , Índice de Massa Corporal , Brasil , Proteína C-Reativa/análise , Calorimetria Indireta , Feminino , Humanos , Inflamação/sangue , Inflamação/etnologia , Pessoa de Meia-Idade , Obesidade Mórbida/etnologia , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
Understanding how opinions spread through a community or how consensus emerges in noisy environments can have a significant impact on our comprehension of social relations among individuals. In this work a model for the dynamics of opinion formation is introduced. The model is based on a nonlinear interaction between opinion vectors of agents plus a stochastic variable to account for the effect of noise in the way the agents communicate. The dynamics presented is able to generate rich dynamical patterns of interacting groups or clusters of agents with the same opinion without a leader or centralized control. Our results show that by increasing the intensity of noise, the system goes from consensus to a disordered state. Depending on the number of competing opinions and the details of the network of interactions, the system displays a first- or a second-order transition. We compare the behavior of different topologies of interactions: one-dimensional chains, and annealed and complex networks.
RESUMO
OBJECTIVE: To analyze the health-related quality of life in patients with osteoporosis and to compare it with the overall population. METHODS: A cross-sectional descriptive study was carried out with 60 female patients of the rheumatology service at a university hospital, in Spain, from April to October 2003. The Short Form-36 (SF-36) questionnaire was applied in order to obtain demographic data, clinical characteristics and data about lifestyles related to health. Patients were classified in age groups. The statistics tests performed were Chi-square, general linear model, Student's t-test. RESULTS: The interviewees' average age was 65.57 years old (SD: +/- 9.7 years), and average time interval for diagnosis was 3.4 +/- 2.84 years. The best scores were in social functioning (89), emotional aspects (72.2), mental health (63), and vitality (53.7). The lowest scores were in general health (45.1), physical capacity (47.7), pain (52.3) and physical aspects (59.9). The patients' average scores were lower than the general Spanish population's scores in the following dimensions: functional capacity, physical aspects, pain and overall health status. The greatest differences between the average SF-36 scores for patients and for the overall Spanish population were in the age group ranging from 55 to 64 years old. Scores were lower or similar to the general Spanish population in all other dimensions of the questionnaire. No significant associations were found between the dimensions of the SF-36 contemplated in this study and the clinical, demographic and lifestyle data. CONCLUSIONS: The patients presented bad quality of life, particularly with respect to those dimensions that are most relevant with respect to osteoporosis, when compared with the overall Spanish population. The physical dimensions were the ones most affected.