Intraoperative lactate levels and postoperative complications of pediatric cardiac surgery

Objectives: Correlate arterial lactate levels during the intraoperative period of children undergoing cardiac surgery and the occurrence of complications in the postoperative period. Aim: Arterial lactate levels can indicate hypoperfusion states, serving as prognostic markers of morbidity and mortality in this population. Background: Anesthesia for cardiac pediatric surgery is frequently performed on patients with serious abnormal physiological conditions. During the intraoperative period, there are significant variations of blood volume, body temperature, plasma composition, and tissue blood flow, as well as the activation of inflammation, with important pathophysiological consequences. Methods/Materials: Chart data relating to the procedures and perioperative conditions of the patients were collected on a standardized form. Comparisons of arterial lactate values at the end of the intraoperative period of the patients that presented, or not, with postoperative complications and frequencies related to perioperative conditions were established by odds ratio and nonparametric univariate analysis. Results: After surgeries without cardiopulmonary bypass (CPB), higher levels of arterial lactate upon ICU admission were observed in patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93 vs 1.40 mm). For surgeries with CPB, the same association was observed for cardiovascular (2.90 mm x 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs 2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs 2.40 mm). Conclusion: Elevated intraoperative arterial lactate levels are associated with a higher morbidity and mortality in low- and medium-risk procedures, with or without CPB, in pediatric cardiac surgery.

Effect of haematocrit on pump and kidney dysfunction after myocardial revascularization

Objective - Kidney dysfunction is a common complication after cardiac surgery. It occurs in 7 to 31% of the patients. The lowest haematocrit after cardiopulmonary bypass surgery (LHCT) has been identified as a risk factor for kidney dysfunction after cardiac surgery. The aim of this study is to determine whether different levels of haematocrit during cardiopulmonary bypass surgery are related to kidney dysfunction.Methods and results-A prospective study was conducted on consecutive adult patients undergoing myocardial revascularization. Preoperative renal function was assessed by baseline serum creatinine level (CrPre). Peak postoperative creatinine (CrPost) was defined as the highest daily in-hospital postoperative value. Peak fractional change in creatinine (% Delta Cr) was defined as the difference between the CrPre and CrePost represented as a percentage of the preoperative value. The LHTC was defined as the lowest recorded haematocrit prior to weaning from the initial pump run. A category variable was created for haematocrit based on the distribution of values. The category variable had the following cut-off points: less than 23%, 23.1 to 28% and greater than 28.1 %. Lowest haematocrit (26.62 +/- 4.15%), CPB (74.71 +/- 24.90 min), CrPre (1.23 +/- 0.37 mg/dl) and highest CrPost (1.52 +/- 0.47 mg/dl) data varied in near-normal fashion. Statistical significance has been observed in the < 23% lowest haematocrit group (CrIPOD and Cr5POD; P = 0.006) and the 23.1 28% lowest haematocrit level group (CrPre and Cr2POD; P = 0.047). CrPre and Cr5POD did not differ between groups (P > 0.05). The multiple linear regression model confirmed that the determinants for higher %Delta Cr were age, body surface area and preoperative serum creatinine level.Conclusion - The LHTC was not identified as a risk factor for kidney dysfunction after myocardial revascularization.

Avaliação da intensidade de dor e da funcionalidade no pós-operatório recente de cirurgia cardíaca

OBJETIVO: Avaliar a intensidade de dor e o nível de funcionalidade em pacientes submetidos à cirurgia cardíaca nos períodos pré-operatório, 7º pós-operatório e alta hospitalar, relacionando-os entre si. Relacionar funcionalidade com: sexo, faixa etária, primeira cirurgia cardíaca ou reoperação, uso de circulação extracorpórea (CEC), tipo de cirurgia e acompanhamento fisioterapêutico. MÉTODO: Foram estudados 41 pacientes que realizaram cirurgia cardíaca eletiva por toracotomia médio-esternal (TME) no HC da Faculdade de Medicina de Botucatu/UNESP. A intensidade de dor foi avaliada pela escala de VAS e a funcionalidade, pela escala MIF (medida de independência funcional) no domínio físico. RESULTADOS: A intensidade de dor mais elevada foi no 7º pós-operatório comparado com os momentos pré-operatório e alta. No pré-operatório, não houve índice de dor; na alta, a intensidade mediana foi 3 (dor moderada). Os níveis mais elevados de perda funcional ocorreram no 7º pós-operatório, quando comparados com os escores totais do pré-operatório e da alta. Verificou-se correlação significativa entre dor e funcionalidade, demonstrando que o decréscimo do nível de dor entre o 7º pós-operatório e a alta contribuiu para a elevação dos níveis funcionais. CONCLUSÃO: As avaliações realizadas no pré-operatório proporcionaram resultados preditivos a serem alcançados. As avaliações realizadas no 7º pós-operatório e na alta possibilitaram a classificação dos pacientes de acordo com perdas e ganhos, indicando aqueles que necessitavam de maior cuidado e treinamento em suas capacidades.

Transdentinal diffusion and cytotoxicity of self-etching adhesive systems

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of human dentine on the antibacterial activity of self-etching adhesive systems against cariogenic bacteria

Objectives: The incorporation of antibacterial agents into adhesive systems has been proposed to eliminate residual bacteria from dentine. This study used the agar diffusion method to evaluate the antibacterial activity of Clearfil Protect Bond (CPB), Clearfil SE Bond (CSEB), Clearfil Tri-S Bond (C3SB) and Xeno-III (XIII) self-etching adhesive systems, with or without light-activation, against cariogenic bacteria, and to assess the influence of human dentine on the antibacterial activity of these materials.Methods: An aliquot of 10 mu l per material (and individual components) were pipetted onto paper and dentine discs distributed in Petri dishes containing bacterial culture in BHI agar. Positive control was 0.2% chlorhexidine digluconate (CHX).Results: After incubation, the adhesive components of CPB and CSEB, liquid A of XIII and C3SB did not present antibacterial activity when applied to paper discs. The non-light-activated CPB primer + adhesive promoted the greatest inhibition of Streptococcus mutans (p < 0.05), whereas with light-activation, there was no significant difference between primer + adhesive and primer alone. For Lactobacillus acidophilus, CPB primer presented the greatest antibacterial activity in both light-activation conditions (p < 0.05). Regarding the dentine discs, only CHX promoted an inhibitory effect, though less intense than on paper discs (p < 0.05). CHX presented greater antibacterial activity against S. mutans than against L. acidophilus (p < 0.05).Conclusions: Light-activation significantly reduced the antibacterial activity of the self-etching adhesive systems; MDPB incorporation contributed to the effect of adhesive systems against cariogenic bacteria; the components eluted from the adhesive systems were not capable to diffuse through 400 mu m-thick dentine disc to exert their antibacterial activity against cariogenic bacteria. (C) 2008 Elsevier Ltd. All rights reserved.

pH, Calcium Ion Release, and Setting Time of an Experimental Mineral Trioxide Aggregate-based Root Canal Sealer

Introduction: An experimental mineral trioxide aggregate sealer (MTAS) has been developed for use as a root canal sealer. The aim of this study was to evaluate the setting time, pH, and calcium ion release of MTAS compared with white Portland cement (CPB-40; Votorantin Cimentos, Camargo Correa SA, Pedro Leopoldo, MG, Brazil), white MTA Angelus (MTA; Angelus, Londrina, PR, Brazil), and AH Plus (Dentsply DeTrey, Konstanz, Germany). Methods: For the evaluation of setting time, each material was analyzed using Gilmore-type needles. Polyethylene tubes with the materials were immersed in distilled water for the measurement of pH (digital pH meter) and calcium release (atomic absorption spectrophotometry). The evaluations were performed at 3, 6, 12, 24, and 48 hours and 7, 14, and 28 days. Data were analyzed by analysis of variance and the Tukey test at 5% significance level. Results: MTAS showed higher calcium release at all experimental periods, a greater increase in pH up to 48 hours and the longest setting time. Conclusions: MTAS presented favorable properties for its indication as a root canal sealer. (J Endod 2011;37:844-846)

Studies on anti-allergic constituents in the leaves and stems of Anchietia salutaris var. martiana (Violaceae)

The anti-allergic active fractionation of hexane extracts of the leaves and stems of Anchietia salutaris,ar. martiana (family Violaceae) nas performed by monitoring their activities with an in vitro bioassay system measuring the inhibitory effects on induced histamine release from guinea pig lung cells. Three known pentacyclic triterpenes (friedelin, alpha-amyrin, beta-amyrin) were isolated, but these compounds were inactive. Aliphatic hydrocarbons and methyl esters of fatty acids (palmitic, oleic, linoleic, linolenic acids) were detected in active fractions. All compounds isolated were detected for the first time in this medicinal plant.

Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline

In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity.

Tempo de circulação extracorpórea como fator risco para insuficiência renal aguda

OBJETIVO: A insuficiência renal aguda (IRA) no pósoperatório (PO) de cirurgia cardíaca é complicação grave. O objetivo deste trabalho é avaliar o tempo de circulação extracorpórea (CEC) como fator de risco para IRA. MÉTODO: Foram avaliados 116 pacientes de um único centro, submetidos a cirurgia cardíaca com CEC. Foram avaliados os dados demográficos, características clínicas, variáveis intra e pós-operatórias. A creatinina sérica e o clearance de creatinina foram avaliados até o 5ºPO. IRA foi definida como necessidade de diálise. Os pacientes foram estratificados em dois grupos: grupo CEC< 70 min e grupo CEC> 90min. RESULTADOS: O aumento médio da creatinina sérica no PO foi 0,18+0,41 no grupo CEC<70min e 0,42+0,44 no grupo CEC>90min (p=0,005). Diálise foi necessária em 1,3% dos pacientes do grupo CEC<70min, e em 12,5% do grupo CEC> 90min (p=0,018). O risco relativo para diálise foi 1,12 (IC 95%, 1,00-1,20) para CEC>90min. Não houve diferença para mortalidade (5,2 versus 7,5%, p=0,631). CONSLUSÃO: O desenvolvimento de IRA no pós-operatório de cirurgia cardíaca foi observado em pacientes com tempo de CEC superior a 90 minutos, embora o clearance de creatinina não tenha demonstrado alteração entre os grupos.

Comparative investigation of the cleavage step in the synthesis of model peptide resins: Implications for N-alpha-9-fluorenylmethyloxycarbonyl-solid phase peptide synthesis

Based on our studies of the stability of model peptide-resin linkage in acid media, we previously proposed a rule for resin selection and a final cleavage protocol applicable to the N-alpha-tert-butyloxycarbonyl (Boc)-peptide synthesis strategy. We found that incorrect choices resulted in decreases in the final synthesis yield, which is highly dependent on the peptide sequence, of as high as 30%. The present paper continues along this line of research but examines the N-alpha-9-fluorenylmethyloxycarbonyl (Fmoc)-synthesis strategy. The vasoactive peptide angiotensin II (All, DRVYIHPF) and its [Gly(8)]-All analogue were selected as model peptide resins. Variations in parameters such as the type of spacer group (linker) between the peptide backbone and the resin, as well as in the final acid cleavage protocol, were evaluated. The same methodology employed for the Boc strategy was used in order to establish rules for selection of the most appropriate linker-resin conjugate or of the peptide cleavage method, depending on the sequence to be assembled. The results obtained after treatment with four cleavage solutions and with four types of linker groups indicate that, irrespective of the circumstance, it is not possible to achieve complete removal of the peptide chains from the resin. Moreover, the Phe-attaching peptide at the C-terminal yielded far less cleavage (50-60%.) than that observed with the Gly-bearing sequences at the same position (70-90%). Lastly, the fastest cleavage occurred with reagent K acid treatment and when the peptide was attached to the Wang resin.

Fmoc-POAC: [(9-fluorenylmethyloxycarbonyl)-2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid]: A novel protected spin labeled beta-amino acid for peptide and protein chemistry

The stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (TOAC) is the only spin labeled amino acid that has been used to date to successfully label peptide sequences for structural studies. However, severe difficulty in coupling the subsequent amino acid has been the most serious shortcoming of this paramagnetic marker. This problem stems from the low nucleophilicity of TOAC's amine group towards the acylation reaction during peptide chain elongation. The present report introduces the alternative beta -amino acid 2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid (POAC), potentially useful in peptide and protein chemistry. Investigations aimed at addressing the stereochemistry of this cyclic molecule through X-ray diffraction measurements of crystalline and bulk samples revealed that it consists only of the trans conformer. The 9-fluorenylmethyloxyearbonyl group (Fmoc) was chosen for temporary protection of the POAC amine function, allowing insertion of the probe at any position in a peptide sequence. The vasoactive octapeptide angiotensin II (AII, DRVYIHPF) was synthesized by replacing Pro(7) with POAC. The reaction of Fmoc-POAC with the peptidyl-resin occurred smoothly, and the coupling of the subsequent amino acid showed a much faster reaction when compared with TOAC. POAC(7)-AII was obtained in good yield, demonstrating that, in addition to TOAC, POAC is a convenient amino acid for the synthesis of spin labeled peptide analogues. The present findings open the possibility of a wide range of chemical and biological applications for this novel beta -amino acid derivative, including structural investigations involving its differentiated bend-inducing characteristics.

The influence of cardiopulmonary bypass operation on the biodistribution of 99mTc-HMPAO-labelled granulocytes – Evaluation in pigs by planar scintigraphy and section-analyses

Aim of the study was to evaluate the influence of an extra corporal perfusion (cardiopulmonary bypass operation - cpb) on activation and biodistribution of Tc-99m labelled granulocytes in pigs with and without inhibition of the granulocytes by a leukocyte inhibition module (LIM). The cpb is often related to an activation of granulocytes resulting in an inflammatory answer. The biological mechanisms are unsolved yet. First trials of our group showed that LIM may inhibit the activation of neutrophils and therefore antagonize a cpb-caused impairment of cardiac function. This study is the continuation of these experiments with a higher number of animals and the focus on scintigraphic imaging. Animals, material, methods: 39 German landrace pigs were subdivided into three groups: group A (control) median sternotomy without cpb, group B with cpb, group C with LIM in addition to cpb. After labelling with Tc-99m-HMPAO autologues granulocytes were reinjected. Subsequently to cpb, the animals underwent scintigraphic imaging. Quantification was performed with ROI evaluation and with tissue samples (section analysis) examined in a well counter. Results:A high uptake of Tc-99m-HMPAO was found in the liver. The count rates in brain, heart, lung, spleen and kidneys were far below. The amount of Tc-99m-activity in the organ related to the half life corrected administered activity [%] was for the tissue samples (group A/B/C): brain 0.01/0.02/0.03; lung 12.1/8.3/11.5; heart 0.35/0.54/0.42; kidney 1.24/0.87/1.02; spleen 4.0/4.0/4.5, liver 16.8/20.9/19.6. The count rates determined by ROI-evaluation of the scintigraphic images related to the total count rate in the image [%] were (group A/B/C): brain 1.1/0.9/1.0; lung 15.6/10.4/12.2; heart 4.0/3.5/3.4; kidney 4.0/2.9/3.2; spleen 7.6/7.7/9.5, liver 23.1/36.7/31.4. A significant difference in the tracer uptake between the groups could neither be detected by scintigraphic imaging nor evaluation of tissue samples. Conclusion: Scintigraphic imaging as well as section analysis showed a comparable biodistribution of the tracer. Therefore, the initial results of our group were not confirmed with a considerably higher number of animals. Neither cpb nor the use of the LIM influenced distribution of Tc-99m-labelled granulocytes in pigs significantly.

Evaluation of Strychnos pseudoquina St. Hil. leaves extract on gastrointestinal activity in mice

Strychnos pseudoquina St. Hil. (Loganiaceae) was investigated for its ability to protect the gastric mucosa against injuries caused by non-steroidal anti-inflammatory drugs (piroxicam) and a necrotizing agent (HCl/EtOH) in mice. The MeOH extract and enriched alkaloidic fraction (EAF) provided significant protection in experimental models wheer used at doses of 250 and 1000 mg/kg. In vivo tests were carried out to evaluate for possible toxic effects and no mortality was observed up to the 5 g/kg dose level. Phytochemical investigation led to the isolation of a new indole alkaloid, which elucidated the observed pharmacological effects. © 2005 Pharmaceutical Society of Japan.

Myeloperoxidase inhibitory and radical scavenging activities of flavones from Pterogyne nitens

Two new flavone glucosides, nitensosides A and B (1, 2), together with four known compounds, sorbifolin (3), sorbifolin 6-O-β-glucopyranoside (4), pedalitin (5), and pedalitin 6-O-β-glucopyranoside (6) were isolated from Pterogyne nitens. Their structures were elucidated from 1D and 2D NMR analysis, as well as by high resolution mass spectrometry. All the isolated flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. The most active compound, pedalitin, exhibited IC 50 value of 3.75 nM on MPO. Additionally, the radical-scavenging capacity of flavones 1-6 was evaluated towards ABTS and DPPH radicals and compared to standard compounds quercetin and Trolox®. © 2008 Pharmaceutical Society of Japan.

Projeto Comédia Popular Brasileira da Fraternal Companhia de Arte e Malas-Artes (1993-2008): trajetória do ver, ouvir e imaginar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)