Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Families with food allergy (FA) are at risk of reduced quality of life and elevated anxiety. A moderate level of anxiety may be beneficial to sustain vigilance for food avoidance; however, excessive anxiety may increase risk for burden and maladjustment. The current study presents a framework for understanding the patterns of adaptation to FA across families and to identify typologies of families that would benefit from intervention. METHODS: Participants included 57 children, 6-12 years old with documented FA, and their mothers. Families were assessed using the Food Allergy Management and Adaptation Scale. Families also completed measures of quality of life, anxiety, FA management, and psychosocial impairment. RESULTS: A hierarchical cluster analysis revealed that 56 of the 57 families of food-allergic children were categorized into four groups that differed on their adequacy of family FA management, levels of anxiety, and balanced psychosocial functioning: balanced responders (n = 23; 41%), high responders (n = 25; 45%), and low responders (n = 3; 5%). The fourth group, anxious high responders (n = 5; 9%), was characterized by extremely high maternal FA anxiety scores and low scores for balanced integration of FA management and psychosocial functioning. Families in clusters differed across illness and psychosocial outcome variables. CONCLUSION: Families with FA were characterized by patterns of FA management, anxiety, and ability to integrate FA demands into daily life. Identified adaptation patterns correspond with clinical impressions and provide a framework for identifying families in need of intervention.
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Adaptação Psicológica , Família/psicologia , Hipersensibilidade Alimentar/epidemiologia , Ansiedade , Criança , Análise por Conglomerados , Gerenciamento Clínico , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/prevenção & controle , Hipersensibilidade Alimentar/terapia , Humanos , Masculino , Vigilância da População , Qualidade de Vida , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND/OBJECTIVES: Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting. SUBJECTS/METHODS: Twenty subjects (age range 20-35 years, body mass index=19-26 kg m(-)(2)) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the 'morning effect', that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. RESULTS: Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the-curve for glucose (-1800; -2564,-1036 mg dl(-1) × h, P<0.001), log-insulin (-0.19; -0.30,-0.07 µU ml(-1) × h; P=0.001) and fatty free acid concentrations (-16.1;-30.0,-2.09 mmol l(-1) × h; P=0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. CONCLUSIONS: The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.
Assuntos
Metabolismo Basal/fisiologia , Ritmo Circadiano , Carboidratos da Dieta/metabolismo , Proteínas Alimentares/metabolismo , Ingestão de Energia , Metabolismo Energético/fisiologia , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Calorimetria Indireta , Estudos Cross-Over , Jejum , Feminino , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Atividade Motora , Fenômenos Fisiológicos da Nutrição , Termogênese/fisiologiaRESUMO
BACKGROUND: In order to attract obese adolescents who are often reluctant to engage in traditional exercise, new forms of physical activity are needed. OBJECTIVES: The purpose of the study was to investigate the impact of dance-based exergaming on a diverse sample of obese adolescents' perceived competence to exercise, psychological adjustment and body mass index (BMI). METHODS: A diverse sample of 40 obese adolescents was randomized to either a 10-week group dance-based exergaming programme or a wait-list control condition. Baseline and follow-up measures included adolescent self-reported psychological adjustment and perceived competence to exercise, and maternal report of adolescent psychological adjustment and anthropometric measures. RESULTS: Compared with controls, participants in the dance-based exergaming condition significantly increased in self-reported perceived competence to exercise regularly and reported significant improvement in relations with parents from baseline to end-of-treatment. Maternal report of adolescent externalizing and internalizing symptomatology also decreased from baseline to end-of-treatment. No pre-post differences in BMI were seen within or between conditions. CONCLUSIONS: Results support the positive impact of dance-based exergaming on obese adolescents' psychological functioning and perceived competence to continue exercise.
Assuntos
Dançaterapia , Dança/psicologia , Exercício Físico/psicologia , Obesidade/psicologia , Obesidade/terapia , Adolescente , Índice de Massa Corporal , Feminino , Humanos , Masculino , Relações Pais-Filho , Autoimagem , Jogos de VídeoRESUMO
OBJECTIVES: The aim of this study was to define a method to evaluate the total dose delivered to the rectum during the whole treatment course in six patients undergoing irradiation for prostate cancer using an offline definition of organ motion with images from a cone beam CT (CBCT) scanner available on a commercial linear accelerator. METHODS: Patient set-up was verified using a volumetric three-dimensional CBCT scanner; 9-14 CBCT scans were obtained for each patient. Images were transferred to a commercial treatment planning system for offline organ motion analysis. The shape of the rectums were used to obtain a mean dose-volume histogram (
Assuntos
Tomografia Computadorizada de Feixe Cônico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Reto/diagnóstico por imagem , Idoso , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Reto/patologia , Reto/efeitos da radiaçãoRESUMO
AIMS: The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommends new criteria for diagnosing gestational diabetes. We evaluated the clinical and metabolic characteristics, and pregnancy outcome, in women previously classifiable as 'normal' according to the 4th International Workshop Conference on gestational diabetes criteria, but reclassified as 'abnormal' according to the new recommendations. METHODS: Using the new IADPSG criteria, 3953 pregnancies were retrospectively reclassified as 1815 women with normal glucose tolerance and 2138 with gestational diabetes, 112 (2.8%) of whom would have been classified as normal according to the older criteria. RESULTS: Of the 2138 women classified as abnormal by the new criteria, the 112 women now reclassified as abnormal were younger and had a lower pre-pregnancy BMI than the 2026 women who had also been classified as abnormal by the previous criteria. The 100-g oral glucose tolerance test showed significantly higher glucose levels in these 112 women than in the 1815 women reclassified as normal (P < 0.0001). Caesarean section was significantly more frequent (P < 0.01) and the ponderal index for the newborn significantly higher in these reclassified women than in those classified as normal (P < 0.0001), and their basal glucose levels correlated significantly with the ponderal index (P < 0.05). CONCLUSION: The new criteria for diagnosing gestational diabetes identified a group of women previously classifiable as normal according to the 4th International Workshop Conference criteria, but revealing metabolic characteristics and pregnancy outcomes resembling those of women who would have been considered to have gestational diabetes by the previous criteria.
Assuntos
Glicemia/metabolismo , Diabetes Gestacional/epidemiologia , Hemoglobinas Glicadas/metabolismo , Adulto , Análise de Variância , Diabetes Gestacional/classificação , Diabetes Gestacional/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Guias de Prática Clínica como Assunto , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Medição de RiscoRESUMO
Glycated haemoglobin (HbA(1c)) is considered the 'gold standard' for monitoring metabolic control in diabetes. An International Expert Committee recently recommended HbA(1c) as a better method than measurement of glucose to use in the diagnosis of diabetes, based on its strong association with microvascular complications, a lower day-to-day variability and ease of use, not necessarily in the fasting state. These recommendations have been embraced by the American Diabetes Association (ADA), which stated in its Standards of Medical Care in Diabetes 2010 that "A(1c), fasting plasma glucose or the 2 h 75 g oral glucose tolerance test (OGTT) are appropriate for testing diabetes and assessing the risk of future diabetes," and that "a confirmed A(1c) ≥ 6.5% is diagnostic for diabetes." Measuring HbA(1c) has several advantages over glucose measurements, but its exclusive use should only be considered if the test is conducted under standardised conditions and its limitations are taken into due account. The impact of its use on the epidemiology of diabetes and other categories of glucose intolerance, as seen from recent reports, is also discussed.
Assuntos
Diabetes Mellitus/diagnóstico , Intolerância à Glucose/diagnóstico , Hemoglobinas Glicadas/análise , Glicemia/análise , Saúde Global , Humanos , Guias de Prática Clínica como Assunto , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The current study investigated whether differences existed in health-related quality of life between individuals who self-identified as having childhood-onset asthma and individuals without a chronic illness. Additionally, the relationship between perceived illness intrusiveness and illness uncertainty to health-related quality of life was explored. METHODS: College undergraduates at least 18 years of age who self-identified as having childhood asthma were randomly matched by age and gender to healthy control participants. Participants completed a demographic form, the Mishel Uncertainty in Illness Scale-Community Form, the Illness Intrusiveness Scale, and the SF-36 Health Survey, a measure of health-related quality of life. RESULTS: Participants with asthma had significantly lower scores on the total and mental health-related quality of life scales than did healthy control subjects. There were no significant differences between self-identified participants with asthma and matched healthy control subjects on physical health-related quality of life scales. Illness intrusiveness was not related to either the physical (e.g., physical functioning, general health) or mental health-related quality of life. Higher levels of illness uncertainty were significantly related to higher levels of mental health-related quality of life (e.g., vitality, mental health). In addition, participants with asthma scored significantly lower than healthy controls on the social functioning and role-emotional subscales. CONCLUSION: The current study adds to the extant literature by examining the relationships between illness intrusiveness, illness uncertainty, and health-related quality of life among a young adult population. College students with asthma appear to be at risk for diminished quality of life compared to a healthy comparison group. Further examination of various domains of health-related quality of life among older adolescents and young adults with childhood asthma is needed.
Assuntos
Asma/fisiopatologia , Asma/psicologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Qualidade de Vida , Estudantes , Universidades , Adulto JovemRESUMO
We examined the effects of 2 months of psyllium treatment in optimizing metabolic control and lipoprotein profile, and its postprandial effects on lipids in type II diabetes. We recruited 40 type II diabetic patients who were on sulfonylureas and a controlled diet, sequentially assigning them to psyllium treatment (G1) or to a control group (G2) treated with dietary measures alone. After 2 months of treatment, body mass index, waist circumference, HbA1c (hemoglobin A1c) and fasting plasma glucose levels had significantly decreased in both groups. There were no postprandial differences in the lipoprotein profile between the two groups. Triglycerides were significantly lower in G1, but not in G2. Our study contributes toward elucidating the effects of psyllium on serum lipids, and suggests that psyllium treatment may help in reducing triglycerides (a known risk factor for cardiovascular disease) in type II diabetic patients.
Assuntos
Catárticos/farmacologia , Diabetes Mellitus Tipo 2/sangue , Hipertrigliceridemia/tratamento farmacológico , Fitoterapia , Psyllium/uso terapêutico , Triglicerídeos/sangue , Glicemia/análise , Glicemia/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertrigliceridemia/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Psyllium/farmacologia , Redução de Peso/efeitos dos fármacos , Redução de Peso/fisiologiaRESUMO
Some GDM women show autoantibody positivity during and after pregnancy and pancreatic autoantibodies can appear for the first time in some patients after delivery. Autoantibody positivity is often accompanied by a high frequency of DR3 and DR4 alleles, which are classically related to the development of type 1 diabetes and, although not all studies agree on this point, by an immunological imbalance expressed by the behaviour of the lymphocyte subpopulation, which can be seen as diabetic anomalies overlapping with the immunological changes that occur during pregnancy. It is worth emphasizing that such patients may develop classical type 1 diabetes during and/or after their pregnancy or they may evolve, often some years after their pregnancy, into cases of latent autoimmune diabetes of adulthood (LADA). Autoimmune GDM accounts for a relatively small number of cases (about 10% of all GDM) but the risk of these women developing type 1 diabetes or LADA is very high, so these patients must be identified in order to prevent the severe maternal and fetal complications of type 1 diabetes developing in pregnancy, or its acute onset afterwards. Since women with autoimmune GDM must be considered at high risk of developing type 1 diabetes in any of its clinical forms, these women should be regarded as future candidates for the immunomodulatory strategies used in type 1 diabetes.
Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/imunologia , Feminino , Humanos , Ilhotas Pancreáticas/imunologia , Gravidez , Fatores de RiscoAssuntos
Citocinas/sangue , Diabetes Gestacional/sangue , Mediadores da Inflamação/sangue , Período Pós-Parto/sangue , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Gestacional/imunologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose , Humanos , Período Pós-Parto/imunologia , Gravidez , Terceiro Trimestre da Gravidez/sangue , Regulação para Cima/imunologiaRESUMO
AIMS/HYPOTHESIS: This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. METHODS: The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA(1c), malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. RESULTS: Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 microg/min) and 62 with microalbuminuria (AER > or =20 microg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean +/- SD): fasting plasma glucose 9.41 +/- 2.88 vs 8.19 +/- 1.93 mmol/l, p < 0.05; HbA(1c) 7.97 +/- 1.51 vs 7.39 +/- 1.03%, p < 0.05; MDA 1.18 +/- 0.35 vs 1.02 +/- 0.29 micromol/l, p < 0.05; pentosidine 98.5 +/- 24.6 vs 82.9 +/- 20.9 pmol/ml, p < 0.005; and AGE 13.2 +/- 4.8 vs 10.6 +/- 3.8 microg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA(1c) r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = -0.55, p < 0.001; TRAP r = -0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA(1c) and MDA, but not pentosidine or AGE. CONCLUSIONS/INTERPRETATION: Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.
Assuntos
Albuminúria/metabolismo , Antioxidantes/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estresse Oxidativo/fisiologia , Idoso , Nefropatias Diabéticas/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , OxirreduçãoRESUMO
A new measurement of the cosmic-ray antiproton-to-proton flux ratio between 1 and 100 GeV is presented. The results were obtained with the PAMELA experiment, which was launched into low-Earth orbit on-board the Resurs-DK1 satellite on June 15th 2006. During 500 days of data collection a total of about 1000 antiprotons have been identified, including 100 above an energy of 20 GeV. The high-energy results are a tenfold improvement in statistics with respect to all previously published data. The data follow the trend expected from secondary production calculations and significantly constrain contributions from exotic sources, e.g., dark matter particle annihilations.
RESUMO
The aim of this study was to elucidate the effects of a poor glycemic control on fatty acid composition and desaturase activities in type 2 diabetic patients. Plasma phospholipid fatty acid composition and desaturase activities (estimated from fatty acid product to precursor ratios) were measured in 30 type 2 diabetic patients during poor metabolic control and after achieving a good metabolic control. Significant changes were recorded in the percentages of palmitic, stearic, dihomo-gamma-linolenic, docosatetraenoic and docosapentaenoic acid. The delta-5 desaturase activity was significantly higher with poor than with good metabolic control. The changes identified in plasma phospholipid fatty acid composition and the desaturase activity in type 2 diabetic patients go in the opposite direction to those described in similar conditions in type 1 diabetic patients and may be relevant to a better understanding of the role of metabolic control in the progression of chronic complications in type 2 diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ativação Enzimática , Ácidos Graxos Dessaturases/sangue , Ácidos Graxos/sangue , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Reprodutibilidade dos TestesRESUMO
Thalamo-cortical networks generate specific patterns of oscillations during distinct vigilance states and epilepsy, well characterized by electroencephalography (EEG). Oscillations depend on recurrent synaptic loops, which are controlled by GABAergic transmission. In particular, GABA A receptors containing the alpha3 subunit are expressed predominantly in cortical layer VI and thalamic reticular nucleus (nRT) and regulate the activity and firing pattern of neurons in relay nuclei. Therefore, ablation of these receptors by gene targeting might profoundly affect thalamo-cortical oscillations. Here, we investigated the role of alpha3-GABA A receptors in regulating vigilance states and seizure activity by analyzing chronic EEG recordings in alpha3 subunit-knockout (alpha3-KO) mice. The presence of postsynaptic alpha3-GABA A receptors/gephyrin clusters in the nRT and GABA A-mediated synaptic currents in acute thalamic slices was also examined. EEG spectral analysis showed no difference between genotypes during non rapid-eye movement (NREM) sleep or at waking-NREM sleep transitions. EEG power in the spindle frequency range (10-15 Hz) was significantly lower at NREM-REM sleep transitions in mutant compared with wild-type mice. Enhancement of sleep pressure by 6 h sleep deprivation did not reveal any differences in the regulation of EEG activities between genotypes. Finally, the waking EEG showed a slightly larger power in the 11-13-Hz band in alpha3-KO mice. However, neither behavior nor the waking EEG showed alterations suggestive of absence seizures. Furthermore, alpha3-KO mice did not differ in seizure susceptibility in a model of temporal lobe epilepsy. Strikingly, despite the disruption of postsynaptic gephyrin clusters, whole-cell patch clamp recordings revealed intact inhibitory synaptic transmission in the nRT of alpha3-KO mice. These findings show that the lack of alpha3-GABA(A) receptors is extensively compensated for to preserve the integrity of thalamo-cortical function in physiological and pathophysiological situations.
Assuntos
Epilepsia/genética , Epilepsia/fisiopatologia , Homeostase/fisiologia , Receptores de GABA-A/genética , Receptores de GABA-A/fisiologia , Sono/genética , Sono/fisiologia , Animais , Nível de Alerta/genética , Nível de Alerta/fisiologia , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Interpretação Estatística de Dados , Eletrodos Implantados , Eletroencefalografia , Eletrofisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Imunofluorescência , Homeostase/genética , Ácido Caínico/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/fisiologia , Técnicas de Patch-Clamp , Fenótipo , Fases do Sono/genética , Fases do Sono/fisiologia , Tálamo/fisiologiaRESUMO
OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.
Assuntos
Diabetes Gestacional/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , GravidezRESUMO
AIM: To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). METHODS: Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), and d-dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. RESULTS: We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD (P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD (P < 0.0001) and in PAD without T2DM (P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy (P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. CONCLUSION: Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/complicações , Neuropatias Diabéticas/complicações , Isquemia/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Caminhada , Coagulação Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Humanos , Claudicação Intermitente/etiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fatores de RiscoRESUMO
Adenosine is a potent modulator of excitatory neurotransmission, especially in seizure-prone regions such as the hippocampal formation. In adult brain ambient levels of adenosine are controlled by adenosine kinase (ADK), the major adenosine-metabolizing enzyme, expressed most strongly in astrocytes. Since ontogeny of the adenosine system is largely unknown, we investigated ADK expression and cellular localization during postnatal development of the mouse brain, using immunofluorescence staining with cell-type specific markers. At early postnatal stages ADK immunoreactivity was prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, as seen best in hippocampus, ADK gradually disappeared from neurons and appeared in newly developed nestin- and glial fibrillary acidic protein (GFAP)-positive astrocytes. Furthermore, the region-specific downregulation of neuronal ADK coincided with the onset of myelination, as visualized by myelin basic protein staining. After postnatal day 14 (P14), the transition from neuronal to astrocytic ADK expression was complete, except in a subset of neurons that retained ADK until adulthood in specific regions, such as striatum. Moreover, neuronal progenitors in the adult dentate gyrus lacked ADK. Finally, recordings of excitatory field potentials in acute slice preparations revealed a reduced adenosinergic inhibition in P14 hippocampus compared with adult. These findings suggest distinct roles for adenosine in the developing and adult brain. First, ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis, thus supporting differentiation and plasticity and influencing myelination; and second, adult ADK expression in astrocytes may offer a mechanism to regulate adenosine levels as a function of metabolic needs and synaptic activity, thus contributing to the differential resistance of young and adult animals to seizures.
Assuntos
Adenosina Quinase/metabolismo , Astrócitos/enzimologia , Encéfalo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios/enzimologia , Fatores Etários , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Encéfalo/enzimologia , Encéfalo/crescimento & desenvolvimento , Contagem de Células/métodos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Técnicas In Vitro , Camundongos , Proteína Básica da Mielina/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Fosfopiruvato Hidratase/metabolismoRESUMO
Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.
Assuntos
Produtos Finais de Glicação Avançada/análise , Fragmentos de Peptídeos/química , Aminas , Diabetes Mellitus , Glucose , Humanos , Reação de Maillard , Espectrometria de Massas , Síndrome Nefrótica , Valores de Referência , Albumina Sérica/química , Soroalbumina Bovina/químicaRESUMO
This study aimed to identify potential immunological markers for predicting type 1 diabetes in patients with gestational diabetes mellitus (GDM) and any immunological impairment in their newborn. In 62 GDM patients and 74 women with normal glucose tolerance (NGT), and their babies, we assessed total lymphocytes, T lymphocyte subsets CD3 and CD8 expressing T cell receptor (TCR) alpha/beta or gamma/delta, CD16 and CD19, pancreatic autoantibodies and cytokines (IL-5, IL-2, soluble receptor IL-2). At delivery, umbilical cord blood samples were taken for lymphocyte subpopulations and cytokine measurements. GDM mothers had higher levels of total lymphocytes, CD8 expressing TCR gamma/delta, and lower levels of CD3 expressing TCR alpha/beta than NGT controls. Insulin-treated GDM mothers had lower CD4 and CD4/CD8 ratios, and higher CD8 and IL-5 than diet-treated GDM or controls. Five women were positive for pancreatic autoantibodies, with lower CD4 (p<0.01) and CD4/CD8 ratios (p<0.05), and higher CD8 (p<0.03) and CD19 than GDM and control mothers negative for autoantibodies. GDM newborn had higher CD8 gamma/delta and lower CD16 than NGT babies. There were no significant differences in TNF-alpha concentrations in the cord blood obtained from the GDM and NGT newborn. In conclusion, GDM women and their newborn have lymphocyte subset impairments, which are more important in patients positive for autoantibodies and/or treated with insulin.