Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.

Restoration of sensory dysfunction following peripheral nerve injury by the polysaccharide from culinary and medicinal mushroom, Hericium erinaceus (Bull.: Fr.) Pers. through its neuroregenerative action

Abstract Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. We investigated the ability of polysaccharide from Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats by daily oral administration. In sensory functional recovery test, the time taken for the rats to withdraw its hind limb from contact with the hot plate was measured. The test revealed acceleration of sensory recovery in the polysaccharide group compared to negative controls. Further, peripheral nerve injury leads to changes at the remotely located DRG containing cell bodies of sensory neurons. Immunofluorescence studies showed that Akt and p38 MAPK were expressed in DRG and strongly upregulated in polysaccharide group after peripheral nerve injury. The intensity of endothelial cells antigen-1 that recognized endothelial cells in the blood vessels of distal segments in crushed nerves was significantly higher in the treated groups than in the negative control group. Our findings suggest that H. erinaceus is capable of accelerating sensory functional recovery after peripheral nerve injury and the effect involves the activation of protein kinase signaling pathways and restoration of blood-nerve barrier.

Disfunção do trato urinário inferior: um diagnóstico comum na prática pediátrica

Disfunção do trato urinário inferior indica uma função anormal do trato urinário inferior para a idade da criança, que pode levar à perda da capacidade coordenada de armazenamento e eliminação de urina. É uma entidade comum em crianças, embora subdiagnosticada na prática clínica, e que, além de representar um risco para o trato urinário superior, causa um constrangimento emocional aos pais e às crianças, devido à incontinência urinária e à frustração em lidar com o problema. A aquisição da continência urinária diurna ocorre na maioria das crianças até os 4 anos e a noturna até os 5 anos de idade. Após esta idade, a incontinência urinária torna-se um problema social. Apesar da importância clínica, muitas vezes, os pais desconhecem os sintomas dessa disfunção. Esse artigo tem como objetivo abordar os principais aspectos relacionados ao diagnóstico dessa disfunção.

Impacto de uma abordagem interdisciplinar em crianças e adolescentes com disfunção do trato urinário inferior (DTUI)

Introdução: A disfunção do trato urinário inferior (DTUI) corresponde a alterações no enchimento ou esvaziamento de urina de causas neurogênicas, anatômicas e funcionais. Objetivo: Avaliar o impacto do tratamento em crianças e adolescentes com DTUI. Métodos: Coorte histórica de 15 anos de seguimento com participação de 192 pacientes (123F, 69M) com idade inicial de 0,1 a 16,8 anos, analisados à admissão (T0) e ao final do seguimento (T1). A maioria dos pacientes era do grupo neurológico (60,4%). O tratamento instituído foi a uroterapia com intervenção comportamental e cognitiva, micção de hora marcada, hidratação oral, dieta laxativa, biofeedback, eletroestimulação sacral, cateterismo vesical intermitente limpo (CIL), terapia anticolinérgica, enema retal, tratamento da infecção do trato urinário (ITU) e, nos casos refratários, procedimentos cirúrgicos, tais como a derivação urinária continente e incontinente (vesicostomia), ampliação vesical e conduto para a realização do enema anterógrado cólico. Resultados: Os principais sintomas foram incontinência urinária diurna (82,3%), enurese noturna não monossintomática (78,6%), incontinência fecal (54,2%) e constipação intestinal (47,9%). Detectou-se redução significativa da infecção do trato urinário (p = 0,0027), da incontinência urinária diurna (p < 0,001), da enurese noturna (p < 0,001), da incontinência fecal (p = 0,010) e do refluxo vesicoureteral (p = 0,01). Houve aumento significativo no uso do CIL (p = 0,021), da terapia com anticolinérgico (p < 0,001) e diminuição da quimioprofilaxia (p < 0,001). Conclusão: Este estudo mostrou que o tratamento da DTUI na criança deve ser individualizado, além de requerer uma monitorização constante dos parâmetros clínicos, laboratoriais e de imagem, para minimizar o risco de lesão renal.

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Erectile dysfunction in cardiovascular risk population

The inability to achieve and to maintain erection, erectile dysfunction, is a bothersome symptom of elderly men. Moreover, there is a high comorbidity between cardiovascular diseases and erectile dysfunction. However, very little is known concerning the risk factors of ED in apparently healthy men without comorbidities affecting the arteries. A cross-sectional population survey was conducted from August 2005 to September 2007 in two rural towns of Harjavalta and Kokemäki in Finland. Excluding those with previously diagnosed cardiovascular diseases, diabetes or chronic kidney disease, every community-dwelling inhabitant was invited to take part in the survey. Of the 2939 45- to 70-year-old men invited, 2049 responded. Selecting those at risk for cardiovascular diseases, 1000 eligible men were examined. According to the International Index of Erectile Function short form 57% of the studied men reported erectile dysfunction. Increasing age, smoking, depressive symptoms, decreasing pulmonary function, sedentary lifestyle, non-marital status and low education level were associated with increasing risk of erectile dysfunction. However, hypertension, diabetes, obesity, hypercholesterolemia were not associated with erectile dysfunction, although these associations have been described in numerous previous studies. Moreover, erectile dysfunction was not associated with increasing risk of pre-diabetes. In apparently healthy men, increasing age, smoking, depressive symptoms, decreasing pulmonary function, sedentary lifestyle, non-marital status, low education level but not hypertension, obesity, hypercholesterolemia, diabetes or pre-diabetes were associated with increasing risk of erectile dysfunction.

Função renal e disfunção cognitiva: estudo transversal de utentes inscritos na unidade de saúde familiar-ponte

Introdução: Estudos recentes demonstram o aumento da prevalência de Disfunção Cognitiva em pacientes com Doença Renal Crônica. Objetivo: Avaliar a referida associação nos utentes inscritos na Unidade de Saúde Familiar-Ponte. Métodos: Estudamos uma amostra constituída por 246 idosos. Avaliamos a função cognitiva por meio do Mini Mental State Examination e a Taxa de Filtração Glomerular com recurso à equação Modification of Diet in Renal Disease. Os valores da Taxa de Filtração Glomerular obtidos (ml/min/1,73 m2) foram distribuídos por três categorias: < 60,00, 60-89,99 e ≥ 90. Recolhemos variáveis adicionais do Serviço de Apoio ao Médico e estudamos os dados recorrendo a análises bivariadas e a modelos de regressão logística. Resultados: Os grupos com Taxa de Filtração Glomerular < 60 e ≥ 90 apresentaram maior prevalência de Disfunção Cognitiva, independentemente de outros fatores. Os odds-ratio foram, respectivamente, de 4,534 (IC95%: 1,257-16,356) e 3,302 (IC95%: 1,434-7,607). Discussão: Conforme a literatura, verificamos maior prevalência de Disfunção Cognitiva no grupo com Taxa de Filtração Glomerular < 60. A elevada prevalência de Disfunção Cognitiva nos utentes com Taxa de Filtração Glomerular ≥ 90 está descrita em alguns estudos e poderá dever-se a situações que induzam a sobrestimação da mesma taxa, como nos estados de caquexia, ou a situações de hiperfiltração glomerular. Conclusão: Constatamos que a relação entre a função renal e a prevalência de Disfunção Cognitiva não foi linear, mas sim parabólica. Novos estudos são necessários para se explicar o porquê deste achado e para se averiguar a necessidade de vigilância da Disfunção Cognitiva em pacientes com alterações da função renal.

Detecção de disfunção renal através da dosagem de creatinina em amostra de gota de sangue seca no papel filtro

Resumo Introdução: A identificação precoce da doença renal crônica (DRC) por meio de amostras de sangue e urina é preconizada em populações de risco devido à elevada morbimortalidade. Objetivo: Apresentamos um teste simples e inovador para dosar a creatinina coletada em gota de sangue seca em papel filtro (PF). Métodos: Cento e seis pessoas em risco de DRC foram rastreadas com avaliação de dados clínicos, exame físico e coleta de sangue de forma convencional e em PF. Com os dados obtidos, foi estimada a taxa de filtração glomerular (e-TFG). Foi considerado diagnóstico de DRC a e-TFG < 60 ml/min. Resultados: A idade dos participantes foi de 57 ± 12 anos, 78 (73,5%) eram mulheres, 43 brancos (40,5%), 36 pardos (34%) e 27 negros (25,5%). O índice de massa corpórea foi de 29,5 ± 6,9 kg/m2, a pressão arterial sistólica foi de 125 mmHg (120-140 mmHg) e a pressão arterial diastólica de 80 mmHg (70-80 mmHg). A sensibilidade pela equação CKD-EPI foi de 94%, a especificidade 55%, o valor preditivo positivo foi de 94%, o valor preditivo negativo de 55% e a acurácia de 90%. A estatística de Bland-Altman mostrou que as diferenças entre os valores de creatinina dos dois testes estão numa faixa relativamente estreita (+ 0,68 mg/dL e -0,55mg/dL) para um desvio padrão de ± 1,96 mg/dL. Conclusão: A dosagem da creatinina coletada em gota de sangue em PF é um teste diagnóstico simples de ser realizado, pouco invasivo e que apresentou uma ótima acurácia, podendo ser útil para rastrear DRC.

Community Care Access Centre accountability reforms: executive director perceptions /

The purpose of this study was to explore how four purposefully selected executive directors of Community Care Access Centres (CCACs) understood the idea of accountability, and how they viewed the accountability reforms that had been imposed on their sector of health care over the previous three years. Data were collected through personal interviews and a reflective journal. An analysis of key documents and the reflective journal informed the data analysis. The findings suggest that executive directors perceive that accountability relationships have shifted since reforms have been implemented. They noted that CCACs have become more accountable to the provincial government at the expense of accountability to the local community. From their perspective, the demand for greater standardization and bureaucratization has left fewer opportunities to adapt programs to meet particular community needs and has slowed the ability to respond quickly to community inquiries and concerns.

Individual differences in risk-taking and associated characteristics : a test of specificity in executive functions /

Multiple measures have been devised by clinicians and theorists from many different backgrounds for the purpose of assessing the influence of the frontal lobes on behaviour. Some utilize self-report measures to investigate behavioural characteristics such as risktaking, sensation seeking, impulsivity, and sensitivity to reward and punishment in an attempt to understand complex human decision making. Others rely more on neuroimaging and electrophysiological investigation involving experimental tasks thought to demonstrate executive functions in action, while other researchers prefer to study clinical populations with selective damage. Neuropsychological models of frontal lobe functioning have led to a greater appreciation of the dissociations among various aspects of prefrontal cortex function. This thesis involves (1) an examination of various psychometric and experimental indices of executive functions for coherence as one would predict on the basis of highly developed neurophysiological models of prefrontal function, particularly those aspects of executive function that involve predominantly cognitive abilities versus processes characterized by affect regulation; and (2) investigation of the relations between risk-taking, attentional abilties and their associated characteristics using a neurophysiological model of prefrontal functions addressed in (1). Late adolescence is a stage in which the prefrontal cortices undergo intensive structural and functional maturational changes; this period also involves increases in levels of risky and sensation driven behaviours, as well as a hypersensitivity to reward and a reduction in inhibition. Consequently, late adolescence spears to represent an ideal developmental period in which to examine these decision-making behaviours due to the maximum variability of behavioural characteristics of interest. Participants were 45 male undergraduate 18- to 19-year olds, who completed a battery of measures that included self-report, experimental and behavioural measures designed to assess particular aspects of prefrontal and executive functioning. As predicted, factor analysis supported the grouping of executive process by type (either primarily cognitive or affective), conforming to the orbitofrontal versus dorsolateral typology; risk-taking and associated characteristics were associated more with the orbitofrontal than the dorsolateral factor, whereas attentional and planning abilities tended to correlate more strongly with the dorsolateral factor. Results are discussed in light of future assessment, investigation and understanding of complex human decision-making and executive functions. Implications, applications and suggestions for future research are also proposed.

Letter from the acting Secretary of War, transmitting information relative to the claims of the State of Massachusetts for payment of the expenses of the militia ordered out by the executive authority of the state, during the late war. --

15th Congress, 1st session, 1817-1818, House. Doc. 81.