Methylene Blue to Neonatal Septic Shock treatment in neonate pigs,

Objective: The authors design an animal model of neonatal sepsis to analyze the treatment of neonatal septic shock with Methylene Blue (MB) in a swine model. Methods: The study design included twenty male newborn pigs divided into four groups: 1) The control group; 2) The sepsis group (induced with lipopolysaccharide); 3) The MB group, and 4) The MB-treated sepsis group. Septic shock was defined as Blood Pressure (BP) dropping 20% below the baseline value. Continuous Blood Pressure (BP), Nitric Oxide (NO) levels, cyclic Guanosine Monophosphate (cGMP), malondialdehyde acid, base excess, lactate, arterial blood gases, hematocrit, and echocardiography were analyzed. Results: The BP of the sepsis group treated with MB showed a slight improvement in the first hour after treatment; however, a significant difference was not observed compared to the untreated sepsis group. Besides hemodynamic stability, the current study did not show symptomatic pulmonary hypertension, suggesting that MB was safe in neonates and children. An improvement in Base Excel (BE) levels after MB administration in septic animals may indicate a possible improvement in microcirculation. Conclusion: The MB improved biomarkers related to septic shock prognosis, although an improvement in the blood levels could not be detected. MB might be a beneficial drug for hemodynamic instability in infants

Gastric emptying in newborn infants and animal model studies

A intolerância gástrica em recém-nascidos prematuros constitui um grande desafio no cuidado neonatal, levando ao uso prolongado de nutrição parenteral e cateteres venosos centrais, aumentando a taxa de infecções neonatais graves e o tempo internação hospitalar dessas crianças. O atraso na maturação da função motora é apontado com o fator determinante da intolerância alimentar dessa faixa etária e a presença de resíduos gástricos a sua principal manifestação clínica. Estudos em adultos mostraram que a velocidade de esvaziamento gástrico é volume dependente, mas em recém-nascidos prematuros este fator não foi adequadamente estudado. O objetivo desse estudo foi avaliar a correlação entre velocidade de esvaziamento gástrico e volume gástrico (em recém-nascidos humanos e ratos), avaliar a influência de fatores pré, peri e pós-natais no esvaziamento gástrico (em recém-nascidos humanos) e estudar os mecanismos fisiológicos que poderiam explicar o efeito do volume na velocidade de esvaziamento gástrico (em ratos). No estudo em humanos, foi realizada a medida da velocidade de esvaziamento gástrico de 20 crianças com idade gestacional entre 28 e 32 semanas através de ultrassonografia, realizada antes e depois da infusão da dieta por sonda orogástrica no primeiro mês de vida. No estudo animal, foi avaliada a velocidade de esvaziamento gástrico de 89 ratos com idade entre 1 e 21 dias através em diferentes tempos de separação materna. Em ambos estudos foi utilizado método de ultrassonografia para estimativa dos valores de esvaziamento gástrico. No modelo animal foram realizadas também medidas de força de contração muscular para diferentes graus de estiramento da parede gástrica. A velocidade de esvaziamento gástrico mostrou correlação importante com o volume gástrico em humanos ((R2 = 0,66 p<0,01) e em ratos (R2 = 0,43 p<0,01) e as crianças com mais de uma semana de vida esvaziam em média 50% do volume oferecido nos primeiros 30 minutos após o término da mamada. As medidas in vitro em ratos mostraram que a contração muscular gástrica induzida por agonista foi diretamente proporcional ao grau do estiramento da parede gástrica e foram mediadas através da via ROCK-2. Em recém-nascidos humanos e ratos o volume gástrico é fator determinante da velocidade de esvaziamento gástrico. Nos ratos, o esvaziamento gástrico não é dependente da idade, mas sim do volume gástrico através da ativação da via ROCK-2, estimulada pelo estiramento da parede gástrica. Em humanos, tipo de leite, uso de ventilação mecânica, tipo de parto, uso de corticosteroide antenatal, uso de antibióticos e/ou antifúngicos, uso de fototerapia não influenciaram a velocidade de esvaziamento gástrico.Feeding intolerance in preterm infants is a major challenge in neonatal care, leading to a prolonged use of parenteral nutrition and central venous catheters, increasing the rate of severe neonatal infections and the length of hospital stay of these infants. The delay in the maturation of motor function is indicated with the determinant factor of the feeding intolerance of this age group and the presence of gastric residuals its main clinical manifestation. Studies in adults have shown that the rate of gastric emptying is volume dependent. But in preterm infants, this factor has not been adequately addressed. The objective of this study was to evaluate the correlation between gastric emptying rate and gastric volume (in human and rat neonates), to evaluate the influence of pre, peri and postnatal factors on gastric emptying (in human newborns) and to study the physiological mechanisms that could explain the effect of volume on gastric emptying rate (in rats). In the human study, the gastric emptying rate of 20 children with gestational age between 28 and 32 weeks was measured by ultrasonography performed before and after infusion of the diet by gavage in the first month of life. In the animal study, the gastric emptying rate of 89 rats aged 1 to 21 days through at different times of maternal separation was evaluated. In both studies, an ultrasound method was used to estimate gastric emptying values. In the animal model muscle strength measurements were also performed for different degrees of gastric wall stretching. Gastric emptying rate showed a significant correlation with the gastric volume in humans ((R2 = 0.66 p <0.01) and in rats (R2 = 0.43 p <0.01) and in the 30 minutes after feeding 50% of the volume had been emptied. In vitro measurements in rats showed that gastric muscle contraction induced by agonist was directly proportional to the degree of gastric wall stretching and were mediated via upregulation of ROCK-2 activity. In human and rat neonates, the gastric volume is a determinant of gastric emptying rate. In rats, gastric emptying is unrelated to postnatal age but dependent on gastric volume, through the activation of the ROCK-2 pathway, wall strain-induced. In humans, milk type, use of mechanical ventilation, type of delivery, use of antenatal corticosteroids, use of antibiotics and/or antifungals, phototherapy use did not influence gastric emptying rate

Adjuvant therapy with sodium alendronate for the treatment of experimental periodontitis in rats

Background: This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature-induced periodontitis in rats. Methods: Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10-5 M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and activated caspase-3 were performed at the furcation region. Results: Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP-positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase-3-positive osteocytes among groups and time points. Conclusion: It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP