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Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.
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INTRODUCTION: Tamoxifen is a non-steroidal anti-oestrogen that acts as an antagonist in breast tissue, neurosensory retina, and retinal pigment epithelium (RPE). The reported incidence of its ocular effects varies between 0.9% and 11%. METHODS: Case series. Multimodal image studies were used to evaluate three female patients who were receiving tamoxifen for breast cancer for the purpose of monitoring and determining whether there are changes after discontinuation of treatment. RESULTS: All three patients showed signs of crystalline retinopathy using spectral domain optical coherence tomography (SD-OCT) during follow-up. CONCLUSION: The follow-up using multimodal imaging studies allowed evaluating the progression of the changes, providing a prognostic assessment. The findings reported (visual acuity and multimodal imaging) confirmed the results of previous studies, indicating that, at a certain level of toxicity, the damage was irreversible.
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Insulin-resistance (IR), of increased cardiovascular risk, is characterized by the production of altered VLDL with greater atherogenicity. Dietary fatty acids influence the type of circulating VLDL. But, it is not clear how dietary fatty acids impact VLDL characteristics in IR. AIM: to evaluate the effects of n-3, n-6 and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL, in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks, SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil (SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids, glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml-1) was characterized by chemical composition and size (size exclusion-HPLC). In comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01), with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit differences in lipid and IR profile, and even favored weight gain and visceral fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 ± 4.4% vs. 68.6 ± 8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5-82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. CONCLUSION: In IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6 PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the recommendations of supplementation with these fatty acids in general diet should be revised.
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VLDL-Colesterol/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Resistência à Insulina , Animais , Doenças Cardiovasculares/metabolismo , Suplementos Nutricionais/análise , Modelos Animais de Doenças , Ácidos Graxos , Humanos , Insulina/sangue , Masculino , Ratos , Ratos Wistar , Triglicerídeos/sangueRESUMO
INTRODUCTION: Similarities of the rat to the human placenta make rat pregnancy models relevant to the study of human gestational diseases. Understanding of species differences is necessary to extrapolate from animal models to humans. We observed alpha-smooth muscle actin (αSMA) expression in rat endovascular trophoblasts (EVasT) and investigated the spatial and temporal expression of smooth muscle (SM) proteins and their potential function in remodeled spiral artery. METHODS: Rat placentas were examined from gestational day 13 to term, and were immunostained for cytokeratin, αSMA, alpha heavy chain of SM myosin, non-muscle myosin, Rho proteins, regulators of SM gene expression, myocardin, an early marker of SM differentiation and endothelin receptors A and B (ETA, ETB). Transmission electron microscopy (TEM) was performed. Modified spiral artery rings were studied ex vivo for endothelin-1- induced contraction. RESULTS: EVasT expressed SM proteins co-localizing with cytokeratin confirming their trophoblastic origin from gestational day 13 to term. Thin fibers, consistent with actin fibers, were observed by TEM, in the cellular localization of αSMA in EVasT. Functional experiments revealed that addition of 10(-7) M endothelin-1 ex vivo reduced vascular lumen area by 11.1% ± 1.8% compared with control. This effect was reduced to only 1.0 ± 1.7% with ETA antagonist, and to 5.4 ± 1.7% contraction by ETB antagonist, p < 0.002, for all. DISCUSSION: The expression of SM proteins in EVasT along with the contractibility of the rat remodeled spiral artery ex vivo, suggest that some vascular tone is potentially maintained by endothelin-1, and may play a role in situations of dysregulation of the vasoactive systems.
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Actinas/metabolismo , Placenta/irrigação sanguínea , Trofoblastos/metabolismo , Animais , Feminino , Microscopia Eletrônica de Transmissão , Placenta/ultraestrutura , Gravidez , Ratos Wistar , VasoconstriçãoRESUMO
Nitric oxide synthase (NOS) plays an important role in hypertensive disorders of pregnancy. In the context of the known association between hyperinsulinemia and hypertension, we studied the expression of the 3 isoforms of NOS (neuronal-nNOS, inducible-iNOS, and endothelial-eNOS) in the placenta and implantation site of our insulin-induced intrauterine growth restriction (IUGR) rat model in which the normal gestational blood pressure decline is abrogated. The fetuses of hyperinsulinemic dams were significantly smaller than those of normal pregnant dams (male fetal weight=4.8+/-0.5 g vs. 5.4+/-0.4 g, hyperinsulinemic vs. control, respectively; female fetal weight=4.5+/-0.5 g vs. 5.1+/-0.4 g, hyperinsulinemic vs control, respectively, p<0.0001). Their placentas weighed less than those of normal pregnant dams (0.44+/-0.08 g in hyperinsulinemic dams vs. 0.50+/-0.09 g, p<0.0001) and their implantation site, designated the mesometrial triangle, was also smaller. Endovascular trophoblasts were found more often and in greater depth in normal pregnant dams. Possibly as a compensatory mechanism, the endovascular trophoblasts formed cell groups rather than a monolayer and occupied a larger portion of the arterial perimeter in arteries of hyperinsulinemic dams. iNOS expression increased by 80% (p<0.0001) and 180% (p=0.045) in placenta and mesometrial triangle of hyperinsulinemic dams, respectively. The expression of eNOS was reduced by 17% (p=0.048) in the placenta and did not change significantly in the mesometrial triangle (p>0.05). nNOS expression was decreased by 37% (p=0.03) in the placenta and increased by 53% (p=0.035) in the mesometrial triangle of hyperinsulinemic dams. Immunohistochemistry revealed prominent expression of iNOS in the placental junctional zone and in interstitial and endovascular trophoblasts in the mesometrial triangle. Assuming a role in trophoblastic invasion, the increased expression of iNOS in hyperinsulinemic dams explains the "compensatory" pattern of trophoblastic invasion. Expression of eNOS was prominent in endothelial cells and weak in endovascular trophoblasts. In our model of gestational hyperinsulinemia-induced IUGR, we found not only differing expression of the 3 NOS isoforms in the cellular elements of the placenta and mesometrial triangle, but also divergent modes of altered NOS isoform expression. These findings suggest, in accordance with other publications, that each isoform may have a distinct function in the placenta and placental bed. The differing expression of the 3 NOS isoforms in the placenta and in the mesometrial triangle in rat IUGR seems to result from the hyperinsulinemia and the resulting IUGR phenotype.
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Implantação do Embrião , Retardo do Crescimento Fetal/metabolismo , Hiperinsulinismo/complicações , Óxido Nítrico Sintase/metabolismo , Placenta/patologia , Complicações na Gravidez/metabolismo , Animais , Pressão Sanguínea , Ciclo Celular , Proliferação de Células , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/patologia , Peso Fetal , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Insulina/administração & dosagem , Insulina/farmacologia , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Tamanho do Órgão , Placenta/metabolismo , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/patologia , Ratos , Ratos Wistar , Trofoblastos/metabolismo , Trofoblastos/patologiaRESUMO
Adiponectin is an important vascular protective substance whose levels are reduced in states of insulin resistance. The relationships between plasma insulin levels and adiponectin are not fully understood, and it is not known whether it is the elevated circulating levels of insulin or insulin resistance that directly affects adiponectin levels. The present study evaluates the direct effect of chronic hyperinsulinemia on plasma adiponectin levels. Male Sprague-Dawley rats were treated with insulin (n=15) administered by a sustained-release implant or were given a sham implantation (n=10) as a control group. Body weight, systolic blood pressure, plasma glucose, triglycerides, insulin, and adiponectin were measured at baseline and after 20 and 40 d of treatment. Insulin-treated rats and controls showed a similar increase in body weight. The insulin-treated group had a significant increase in plasma insulin levels and a decrease in plasma glucose levels compared with the sham group, with no change in blood pressure or triglyceride levels. Adiponectin levels remained unchanged despite the significant increase in insulin levels. High circulating insulin levels do not affect plasma adiponectin levels. These results support the concept that the primary defect that results in insulin resistance and hyperinsulinemia is responsible for the altered plasma adiponectin levels in the metabolic syndrome and type 2 diabetes.
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Adiponectina/sangue , Hiperinsulinismo/sangue , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Doença Crônica , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Insulina/farmacologia , Sistemas de Infusão de Insulina/veterinária , Resistência à Insulina/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Triglicerídeos/sangueRESUMO
Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.
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Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Hipertensão/mortalidade , Resistência Vascular/fisiologia , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Few studies have addressed the link between minor renal dysfunction and mortality in the elderly. AIM: To compare three equations for estimated GFR (eGFR) in assessing renal dysfunction and predicting mortality in an elderly population. DESIGN: Longitudinal observational study. METHODS: We studied 441 people from the Jerusalem Seventy Year Olds Longitudinal Study who had measurements of serum creatinine, all of whom were aged 70 years at study initiation and were living in the community. GFR was estimated based on serum creatinine and using the Cockcroft-Gault (CG), the abbreviated Modification of Diet in Renal Disease (MDRD) and the Mayo Clinic equations. Twelve-year mortality was the main outcome measure. RESULTS: The prevalence of reduced eGFR was 51% using the CG, 34% using MDRD and 16% using the Mayo Clinic equation. eGFR dichotomized by the definition of CKD significantly predicted mortality only with the Mayo Clinic equation (hazard ratio 1.56, 95%CI 1.01-2.39). When eGFR was divided into quartiles and the lowest compared to the highest, all equations predicted mortality. Hazard ratios (95%CI) were 5.48 (1.27-23.65), 7.47 (2.74-20.3), and 7.375 (3.13-17.36), for CG, MDRD, and Mayo Clinic, respectively. DISCUSSION: Reduced eGFR was prevalent in this study group, and associated with mortality. This association was strongest using the Mayo Clinic equation.
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Taxa de Filtração Glomerular/fisiologia , Nefropatias/diagnóstico , Idoso , Estudos de Coortes , Feminino , Previsões/métodos , Humanos , Estimativa de Kaplan-Meier , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Estudos Longitudinais , Masculino , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Glomerular filtration rate (GFR) diminishes with age. Kidney function in the elderly is often assessed by serum creatinine alone, although it is insensitive in this age group. Formulae for predicting GFR are not widely used. AIM: To study the effect of low predicted GFR on mortality. DESIGN: Longitudinal cohort study. SETTING: The community-based Jerusalem Seventy Year Olds Longitudinal Study. METHODS: We studied 445 subjects, all aged 70 years, using questionnaires, a medical examination with history-taking, and standard laboratory tests. Moderate renal insufficiency was defined as a predicted GFR of <60 ml/min, based on the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) equations. RESULTS: Predicted GFR was normally distributed, with a mean +/- SD of 62.4 +/- 15.27 ml/min. Predicted GFR was <60 ml/min in 221 (46%), most of whom had normal serum creatinine. Twelve-year mortality was 38.7% in these 221 vs. 27% in the other 204. The survival advantage was already evident after 3 years. Under Cox proportional hazard analysis using numerous common risk factors as independent variables, lower predicted GFR had a significant mortality risk (hazard ratio 2.108, 95%CI 1.43-3.12, p = 0.0002). DISCUSSION: In community-dwelling elderly people, moderate renal insufficiency as assessed using the CG equation is a strong and independent predictor of mortality. Most of these at-risk patients have 'normal' serum creatinine.
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Creatinina/sangue , Taxa de Filtração Glomerular , Insuficiência Renal/mortalidade , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Israel/epidemiologia , Estudos Longitudinais , Masculino , Insuficiência Renal/fisiopatologiaRESUMO
The European Society of Hypertension (ESH) has issued guidelines for the detection and treatment of hypertension. According to these guidelines, normal 24-h ambulatory blood pressure (ABP) is defined as lower than 125/80 mmHg. Another publication of ESH recommendations for blood pressure (BP) measurement defines normal awake and asleep blood pressure as lower than 135/85 and 120/70 mmHg, respectively. Our aim was to investigate the compatibility of these two recently proposed ABP cutoffs in clinical practice. We analysed 1495 consecutive ABP measurements. In all, 56% of the subjects were female; age 58 +/- 16 years; body mass index 27 +/- 4 kg/m(2); clinic BP 151+/-22/84 +/- 13 mmHg. Two-thirds were treated for hypertension, and 11% for diabetes. Subjects were classified as having normal 24-h BP if the corresponding value was <125/80 mmHg. Normal awake-sleep BP was diagnosed if awake BP was <135/85 mmHg and sleep BP was <120/70 mmHg. Concordance between the cutoffs was found in 93% of the subjects. Among the 7% discordant subjects, 4.5% were hypertensive applying the 24 h, but not awake-sleep, BP values, whereas only 2.5% were hypertensive according to awake-sleep, but not 24 h, BP values (P < 0.005). In Conclusion, in real-life ABP measurement, a good agreement was found between two recently issued ABP normality definitions. However, some subjects are classified as hypertensive only according to one of these methods, more often by the 24-h cutoff of 125/80. This discordance may be significant in large-scale clinical BP monitoring.
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Monitorização Ambulatorial da Pressão Arterial/instrumentação , Monitores de Pressão Arterial/normas , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Guias de Prática Clínica como Assunto , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
A patient is described who had severe hyperplastic gastropathy as the presenting manifestation of systemic lupus erythematosus (SLE). Aggressive immunosuppressive therapy with systemic corticosteroids and immunoglobulins resulted in complete remission of lupus, and a prompt clinical and radiological regression of hyperplastic gastropathy. Hyperplastic gastropathy is an uncommon gastric illness, which is usually idiopathic but rarely is associated with Helicobacter pylori infection, cytomegalovirus infection or lymphocytic gastritis. Three previous case reports have noted a response of idiopathic hyperplastic gastropathy to systemic corticosteroid treatment, yet none of the presented patients had a systemic inflammatory disease. The presented case is the first in the medical literature in which hyperplastic gastropathy is directly linked to the development of clinical and laboratory manifestations of SLE. We suggest that hyperplastic gastropathy be added to the list of rare gastrointestinal manifestations of SLE, and that autoimmune disease be considered a possible cause of hyperplastic gastropathy. As such, any patient with symptomatic idiopathic hyperplastic gastropathy accompanied by other evidence of systemic inflammation should be considered for SLE evaluation and immunosuppressive treatment.
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Gastrite Hipertrófica/etiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Gastropatias/etiologia , Adulto , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Gastropatias/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Non-dipping, ie failure to lower blood pressure during sleep, has been found to be more prevalent in diabetic than in non-diabetic subjects. However, the reasons remain to be clarified. Diabetic patients may wake up more frequently during the night (for instance, due to nocturia). This may result in inclusion of awake blood pressure measurements in the night-time average and thus erroneously raise this average, causing misclassification of patients as non-dippers. However, non-dipping in diabetes may be due to blunted effect of sleep itself on blood pressure secondary to autonomic neuropathy. We undertook this study in order to further clarify this question. We studied 23 diabetic patients, and 23 matched controls who underwent 24-h ambulatory blood pressure monitoring, and reported taking an afternoon nap. Afternoon nap, by virtue of its short duration, is devoid of interruptions, and thus can be used as a model for tiled, non-interrupted sleep. We found that, both in diabetic patients and controls, blood pressure declined during the afternoon nap in a similar magnitude to the night-time decline. However, this decline was significantly blunted in the diabetic patients (13.9 +/- 2.2% decline in diastolic blood pressure during naptime in the diabetic patients, as compared with 24 +/- 2.3% decline in diastolic blood pressure during the siesta in the control group, P < 0.02). The blunted decline of blood pressure during the nap in diabetic patients demonstrates that non-dipping is due to the blunted effect of sleep itself. This can be another facet of autonomic dysfunction seen in diabetes mellitus.
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Diabetes Mellitus Tipo 1/fisiopatologia , Sono/fisiologia , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Every year, millions of Moslems throughout the world fast from sunrise till sunset daily during the month of Ramadan, that is, experience repeated cycles of fasting-refeeding. Studies in animal models have shown that repeated cycles of fasting-refeeding may cause or exacerbate hypertension. Changes in sleeping patterns as well as changes in medication timing may also influence ambulatory blood pressure. We undertook this study in order to examine the effect of the Ramadan fast on treated hypertensive subjects. Seventeen hypertensive subjects were examined, and 24-h blood pressure monitoring was carried out twice, before and during the last week of the Ramadan. All continued their medications, which were all once-daily preparations. Twenty-four hour mean blood pressure as well as average awake and average asleep blood pressure were compared. There was no difference between mean blood pressure before and during the Ramadan (138.5 +/- 18.5/77.2 +/- 8.1 mm Hg vs 136.4 +/- 20.4/75.7 +/- 5.9 mm Hg, P-nonsignificant). Blood pressure load also did not differ before and during Ramadan (systolic load 49% vs. 44%, diastolic load 21% vs. 18%, P-nonsignificant). Weight was reduced by 1.4 +/- 1.6 kg (P < 0.002). We conclude, that according to our findings, treated, hypertensive patients may be assured that, with continuation of previous medications, traditional fasting during the month of Ramadan can be safely undertaken.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Jejum/fisiologia , Hipertensão/tratamento farmacológico , Islamismo , Religião e Medicina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Atenolol/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Sono/fisiologia , Verapamil/uso terapêuticoRESUMO
To assess maternal versus paternal contributions to the familial aggregation of hypertension, we examined family history data from 344 hypertensive probands (69 African American, 153 US Caucasian, 122 Greek Caucasian) ascertained without respect to parental hypertension status. The proportion of hypertensive mothers (81.7, 65.0 and 84.8% for African Americans, US Caucasians and Greek Caucasians, respectively) of these probands was significantly greater than the proportion of hypertensive fathers (50.0, 44.9 and 48.3%, respectively) in all three ethnic groups. The lifetime risk of hypertension was significantly greater for mothers compared with fathers of these hypertensive probands (p<0.001). Examination of the proband's siblings indicated that maternal history of hypertension was associated with greater lifetime risk for hypertension than paternal history (p<0.01). In conclusion, we observe a consistent maternal component in the inheritance of hypertension. Although we cannot separate a maternal genetic from epigenetic or environmental effect, our findings suggest that genetic research should include studies of the mitochondrial as well as nuclear genome. Furthermore, when assessing a patient's risk for hypertension, particular attention should be paid to the maternal family history.
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Hipertensão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/genética , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca/genéticaAssuntos
Inibidores de Ciclo-Oxigenase/efeitos adversos , Insuficiência Cardíaca/complicações , Isoenzimas/antagonistas & inibidores , Lactonas/efeitos adversos , Insuficiência Renal/induzido quimicamente , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Feminino , Fibrose , Insuficiência Cardíaca/patologia , Humanos , Proteínas de Membrana , Pessoa de Meia-Idade , Miocárdio/patologia , Prostaglandina-Endoperóxido Sintases , Insuficiência Renal/complicações , SulfonasRESUMO
Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNO(x)). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with L-arginine (2 g/l in the drinking water) (L-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNO(x) excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10+/-3% increase in SBP was found in P-INS rats, contrasting with a fall of -15+/-4% in P rats (P<0.01). In the L-ARG group at the end of pregnancy, SBP values had fallen by -14+/-2%, to values comparable with those of P rats. The increase in UNO(x) excretion was 175+/-38% in P rats, 106+/-12% in L-ARG rats and 41+/-8% in P-INS rats (P<0.01 compared with P and L-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and L-ARG rats. Thus the blood pressure response to L-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.
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Arginina/uso terapêutico , Hiperinsulinismo/complicações , Hipertensão/etiologia , Complicações Cardiovasculares na Gravidez/etiologia , Animais , Doença Crônica , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/urina , Nitratos/urina , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/urina , Ratos , Ratos Wistar , Fatores de RiscoRESUMO
Nondipping, ie, failure to reduce blood pressure by >/=10% during the night, is considered an important prognostic variable of 24-hour ambulatory blood pressure monitoring. However, some people wake up at night to urinate. Usually, 24-hour ambulatory blood pressure monitoring-derived blood pressure includes these rises in the nighttime blood pressure mean. We identified 97 subjects undergoing 24-hour ambulatory blood pressure monitoring who reported waking up at night to urinate. We assessed the 24-hour ambulatory blood pressure monitoring first using total daytime and total nighttime means and then using actual daytime awake and nighttime asleep (as reported by the patient) means. Nocturnal decline in blood pressure was 14.4+/-8.5/11.8+/-6.1 mm Hg with the first method and 17.1+/-8.3/13.8+/-5.9 mm Hg with the second one (P<0.00001). Although the absolute difference between the nocturnal blood pressure declines calculated by the 2 methods was small, the effect on nocturnal dip was profound. Average systolic blood pressure dipping was 10.1% by the total day-total night method and 12.0% by the actual day awake-night asleep method (P=0.00001), and that of diastolic blood pressure was 14.2% and 16.7%, respectively (P=0.00001). The prevalence of systolic blood pressure nondipping decreased from 42.2% by the first method to 31.9% by the second method (P=0.0056), and that of diastolic blood pressure nondipping decreased from 22.6% to 11.3% (P=0.00001). Inclusion of awake blood pressure measurements during the night obscured the normal dipping pattern in people who woke up to urinate. Thus, taking into account people's actual behavior increases the accuracy of the results.