Changes in aortic pulse wave components, pulse pressure amplification, and hemodynamic parameters of children and adolescents with type 1 diabetes.

BACKGROUND/OBJECTIVE: Type 1 diabetes mellitus (DM1) presents important risk factors for cardiovascular events. OBJECTIVE: To compare the components of the aortic pulse wave (APW) and the hemodynamic parameters among children and adolescents with DM1 and healthy individuals. METHODS: This is a cross-sectional study, with 36 children and adolescents diagnosed with DM1 (11.9 ± 3.2 years) matched by sex and age with the control group (n = 36, 12.4 ± 2.9 years). The components of the APW and the hemodynamic parameters were evaluated non-invasively, using Mobil-O-Graph. RESULTS: On the week of the evaluation, DM1 patients presented glycated hemoglobin (hemoglobin A1C [HbA1c]) of 9.48 ± 2.22% and fasting glycemia of 222.58 ± 93.22 mg/dL. Augmentation index (AIx@75), reflection coefficient, and augmentation pressure (AP) were significantly higher in the DM1 group (29.0 ± 9.7%, 63.0 ± 7.9, and 7.8 ± 2.7 mm Hg, respectively) compared with the control group (20.6 ± 7.9%, 53.4 ± 9.1 and 4.9 ± 2.1 mm Hg, respectively). The systolic volume (52.6 ± 11.9 and 60 ± 12.4 mL) and the cardiac output (4.3 ± 0.5 and 4.6 ± 0.5 L/min) decreased in the DM1 group in relation to the control group. The pulse pressure amplification (PPA) was significantly lower in the DM1 group (1.4 ± 0.15) compared with the control group (1.6 ± 0.17). PPA correlated negatively with total vascular resistance (TVR), AP and reflection coefficient, and positively with cardiac index in both groups. In the DMI group, the AIx@75 correlated negatively with age, height, systolic volume, and PPA, and correlated positively with the TVR and reflection coefficient. CONCLUSIONS: These results confirm the presence of arterial stiffness in this population and extend the knowledge, showing, for the first time, the reduction of PPA in the DM1 group.

Curine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²âº channels and decreases intracellular Ca²âº transients in A7r5 cells.

Curine is a novel bisbenzylisoquinoline alkaloid that has previously been reported as a vasodilator. The underlying mechanism(s) of the vasodilator effect of curine remains to be characterized. In this study, we investigated the cellular mechanism that is responsible for the vasodilator effect of curine in the rat aorta. The vasorelaxant activity of curine was recorded using a myograph. Ca(2+) currents in A7r5 cells were measured using the whole-cell patch-clamp technique. Intracellular Ca(2+) transients were determined using confocal microscopy. In a concentration-dependent manner, curine inhibited contractions elicited by high extracellular K(+) and Bay K8644 in the rat aorta and reduced the rise in the intracellular Ca(2+) concentration induced by membrane depolarization in response to an increase in extracellular K(+) concentration in vascular smooth muscle cells. Moreover, curine decreased the peak amplitude of L-type Ca(2+) currents (I(Ca,L)) in a concentration-dependent manner without changing the characteristics of the current density vs. voltage relationship and the steady-state activation of I(Ca,L). Furthermore, curine shifted the steady-state inactivation curve of I(Ca,L) toward more hyperpolarized membrane potentials. None of the following modified the effect of curine on I(Ca,L) amplitude: 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterases; dibutyryl cyclic AMP, an activator of protein kinase A (PKA); or 8-Br-cyclic GMP, an activator of protein kinase G (PKG). Our results showed that curine inhibited the L-type voltage-dependent Ca(2+) current in rat aorta smooth muscle cells, which caused a decrease in intracellular global Ca(2+) transients that led to vasorelaxation.

Phosphoinositide-3 kinase gamma activity contributes to sepsis and organ damage by altering neutrophil recruitment.

RATIONALE: Sepsis is a leading cause of death in the intensive care unit, characterized by a systemic inflammatory response (SIRS) and bacterial infection, which can often induce multiorgan damage and failure. Leukocyte recruitment, required to limit bacterial spread, depends on phosphoinositide-3 kinase γ (PI3Kγ) signaling in vitro; however, the role of this enzyme in polymicrobial sepsis has remained unclear. OBJECTIVES: This study aimed to determine the specific role of the kinase activity of PI3Kγ in the pathogenesis of sepsis and multiorgan damage. METHODS: PI3Kγ wild-type, knockout, and kinase-dead mice were exposed to cecal ligation and perforation-induced sepsis and assessed for survival; pulmonary, hepatic, and cardiovascular damage; coagulation derangements; systemic inflammation; bacterial spread; and neutrophil recruitment. Additionally, wild-type mice were treated either before or after the onset of sepsis with a PI3Kγ inhibitor and assessed for survival, neutrophil recruitment, and bacterial spread. MEASUREMENTS AND MAIN RESULTS: Both genetic and pharmaceutical PI3Kγ kinase inhibition significantly improved survival, reduced multiorgan damage, and limited bacterial decompartmentalization, while modestly affecting SIRS. Protection resulted from both neutrophil-independent mechanisms, involving improved cardiovascular function, and neutrophil-dependent mechanisms, through reduced susceptibility to neutrophil migration failure during severe sepsis by maintaining neutrophil surface expression of the chemokine receptor, CXCR2. Furthermore, PI3Kγ pharmacological inhibition significantly decreased mortality and improved neutrophil migration and bacterial control, even when administered during established septic shock. CONCLUSIONS: This study establishes PI3Kγ as a key molecule in the pathogenesis of septic infection and the transition from SIRS to organ damage and identifies it as a novel possible therapeutic target.

(S)-reticuline induces vasorelaxation through the blockade of L-type Ca(2+) channels.

In Brazil, various species of the genus Ocotea are used in folk medicine for treating several diseases. The chemical characterization of this plant showed the presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the major component of which is (S)-reticuline. The present study investigated whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca(2+) channels. Tension measurements and patch clamp techniques were utilized to study the effects of (S)-reticuline. Whole-cell Ca(2+) currents were measured using the A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl(2)- and KCl-induced contractions and elicited vasorelaxation. It also reduced the voltage-activated peak amplitude of I (Ca,L) in a concentration-dependent manner. (S)-reticuline did not change the characteristics of current density vs. voltage relationship. (S)-reticuline shifted leftwards the steady-state inactivation curve of I (Ca,L). The application of dibutyryl cyclic adenosine monophosphate to the cell decreased the amplitude of Ca(2+) currents. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of (S)-reticuline caused further inhibition of the Ca(2+) currents suggesting an additive effect. The results obtained show that (S)-reticuline elicits vasorelaxation probably due to the blockade of the L-type voltage-dependent Ca(2+) current in rat aorta. The reported effect may contribute to the potential cardioprotective efficacy of (S)-reticuline.

Aspectos psicossociais e sexuais de gestantes adolescentes em Belém-Pará / Psychosocial and sexual aspects of pregnant adolescents at Belém-Pará

A gravidez na adolescência determina com muita frequência consequências psicossociais para as gestantes adolescentes. Foram avaliados alguns aspectos pessoais-sociais e sexuais de 120 gestantes, na faixa etária de 12 a 18 anos, atendidas no Serviço de Pré-Natal de Risco da Secretaria de Saúde do Estado, durante a primeira consulta do pré-natal e independentemente da idade gestacional, de 10/1991 a 04/1992, Belém-Pará. Os resultados demonstraram que a menarca ocorreu em maior frequência entre 12 e 13 anos (mediana 12,2 anos); 50,9 por cento da iniciaçäo sexual se deu com até 14 anos e 56,6 por cento das gestantes avaliadas encontravam-se na faixa etária de até 16 anos. A maioria (98,4 por cento) das adolescentes iniciaram vida sexual com namorados; 72,5 por cento por desejo próprio e 67,5 por cento com até um ano de namoro, sendo esta atitude mais frequente (79,4 por cento) entre aquelas mais jovens (12-16 anos). A principal fonte de informaçäo sobre sexualidade referida pelas adolescentes foram os colegas (65,1 por cento) e, quanto ao conhecimento e uso da contracepçäo, 55,9 por cento conheciam algum método, entretanto, apenas 13,3 por cento faziam uso. Do total das adolescentes, 96,7 por cento eram dependentes da família e 30,3 por cento e 32,1 por cento, respectivamente, referiram ter abandonado a escola antes ou durante a gestaçäo. As adolescentes, principalmente as mais jovens, demonstraram pouco conhecimento e uso da contracepçäo; desinformaçäo nas questöes da sexualidade e altos índices de iniciaçäo sexual precoce, fatores estes que podem ter contribuído para a ocorrência de gravidez precoce entre as adolescentes .