Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial / Efeito da pré‐ administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Abstract Background and objectives Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results The EC50 of propofol was lower in Group C (2.32 µg.mL−1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL−1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL−1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL−1, 95% CI 2.33-2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). Conclusion High-dose FA (0.75 mg.kg−1 or 1 mg.kg−1) reduces the EC50 of propofol, and 1 mg.kg−1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Resumo Justificativa e objetivos A administração pré‐operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol. Métodos Noventa e seis pacientes (ASA I ou II, com idades de 18-65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up‐and‐down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo‐controlada 0,5 µg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados A CE50 do propofol foi menor no Grupo C (2,32 µg.mL‐1, Intervalo de Confiança de 95% [95% IC] 1,85-2,75) e D (2,39 µg.mL‐1, 95% IC 1,91-2,67) do que no Grupo A (2,96 µg.mL‐1; 95% IC 2,55-3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 µg.mL‐1, 95% IC 2,33-2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05). Conclusão FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré‐administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Immune response of calves inoculated with proteins of Anaplasma marginale bound to an immunostimulant complex / Resposta imune de bezerros inoculados com proteínas de Anaplasma marginale ligadas a um complexo imunoestimulante

Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX) adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5) to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1); 2 calves were inoculated with ISCOMATRIX adjuvant (G2); and 4 calves received saline (G3). Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05), and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05). The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

Apesar dos avanços da imunologia, patologia e genética de Anaplasma marginale, a prevenção em bovinos ainda é baseada nas vacinas vivas atenuadas, na terapia com antibiótico e estabilidade enzoótica dos rebanhos bovinos. No presente estudo, avaliou-se o uso de um complexo imunoestimulante (ISCOMATRIX), associado às proteínas recombinantes de superfície (rMSP1a, rMSP1b, rMSP4 e rMSP5) para melhorar a resposta imune humoral desencadeada em bezerros, principalmente por IgG2. Dez animais foram divididos em três grupos: 4 bezerros foram inoculados com o ISCOMATRIX/rMSPs (G1), 2 bezerros foram inoculados com ISCOMATRIX adjuvante (G2) e 4 bezerros receberam salina (G3). Três doses vacinais foram administradas em intervalos de 21 dias. No G1, os bezerros apresentaram aumentos significativos nos níveis de IgG total, IgG1 e IgG2 21 dias após a segunda inoculação, em comparação com o grupo de controle (p <0,05). Nos bezerros do G1 esses níveis de anticorpos permaneceram acima do ponto de corte 28 dias após a terceira inoculação (p < 0,05). Os soros pós-imunização de bezerros do G1 reagiram especificamente com cada uma das rMSPs utilizadas. Em conclusão, o ISCOMATRIX/rMSPs induziu soroconversão antígeno-específica em bezerros. Portanto, se justifica a realização de ensaios adicionais para explorar a proteção induzida pela rMSPs, tanto sozinhas como em conjunto com novas proteínas identificadas com epítopos subdominantes.

Transferência de lípides para a lipoproteína de alta densidade (HDl) em mulheres com diabetes melito tipo 1 / Lipid transfer to HDl in women with type 1 diabetes

INTRODUÇÃO: Os portadores de diabetes melito tipo 1 (DM1) possuem aumentado risco de doença cardiovascular e, ainda assim, podem apresentar perfil lipídico normal. Para esclarecer se os níveis normais de HDL podem ocultar defeitos na função, foram estudados a transferência de lípides para a HDL em DM1. MÉTODOS: Vinte e uma mulheres jovens portadoras de DM1 foram comparadas com 21 mulheres não-diabéticas. Nanoemulsões foram usadas como doadoras de lípides para HDL: uma marcada com ³H-triglicérides e 14C-colesterol livre e outra com ³H-éster de colesterol e 14C-fosfolípides. Após 1 hora de incubação com amostras de plasma, seguida por precipitação química, o sobrenadante, contendo HDL, teve a radioatividade contada. RESULTADOS: Nenhuma diferença foi encontrada nas transferências dos ésteres de colesterol, triglicérides, colesterol livre e fosfolípides para as HDL. CONCLUSÃO: A transferência de lípides para a HDL não está afetada em portadoras de DM1. Isso sugere que a doença não altera a composição de lipoproteínas e a ação de proteínas de transferência.

INTRODUCTION: People with type 1 diabetes mellitus (T1DM) have an increased risk of cardiovascular disease and may still have a normal lipid profile. In order to clarify whether normal HDL cholesterol levels may conceal defects in HDL function, we have studied the transfer of lipids to HDL in T1DM. METHODS: Twenty-one young women with T1DM were compared with 21 non-diabetic women. Nanoemulsion preparations were used as lipid donor to HDL: one labeled with ³H-triglycerides and 14C-free cholesterol and the other with ³H-cholesteryl esters and 14C-phospholipids. These preparations were incubated with plasma samples for 1h. After chemical precipitation, the supernatant containing HDL was counted for radioactivity. RESULTS: No difference in transfer was observed to nanoemulsion HDL from cholesteryl esters, triglycerides, free cholesterol and phospholipids. CONCLUSION: Simultaneous lipid transfer to HDL was not affected in T1DM patients. This suggests that the disease does not alter lipoprotein composition and transfer protein action in such way as to disturb HDL metabolism.

Adverse effects of mercuric chloride on thyroid of mice, Musculus albinus and pattern of recovery of the damaged activity.

The protective role of "essentiale phospholipids" (EPL) on mercury induced thyroid dysfunction with special reference to cholesterol, thyroid peroxidase and thyroxine activity in mice were investigated. The animals were treated with 0.5 ml/day of 0.5 ppm aqueous mercuric chloride for a period of 7, 14 and 21 days. For the recovery 175 mg of EPL was given to mice (already treated with HgCl2) for a period of 7, 14 and 21 days. Daily treatment of HgCl2 for 7, 14 and 21 days decreased serum cholesterol, TPO and T4 activity. Simultaneous administration of EPL (25 mg/mice) restored thyroid function in mice by maintaining serum thyroid hormone concentration almost normal. It increased serum cholesterol, TPO and T4 activity. It appears that the protective effect of EPL against HgCl2 induced thyroid dysfunction is mediated through its antioxidative action.

Laboratory identification of lupus anticoagulants using the combination of activated partial thromboplastin time and Russell's viper venom at two phospholipid concentrations.

The most appropriate combination of tests for lupus anticoagulants (LA) is unknown. The standard double centrifugation method to prepare plasma was inadequate for platelet elimination, interfering with kaolin clotting time and mixing studies. In the present study, the percentage correction of activated partial thromboplastin time (APTT) and Russell's viper venom time (RVVT) by high compared with low concentrations of phospholipid was used for both screening and confirmation of LA. Abnormality in either one was reported as positive. The specificity of the tests in 122 individuals without LA was 100 per cent for RVVT and 96.7 per cent for APTT, which yielded false positive by heparin. The mixing study was omitted from the authors' strategy without decreasing the specificity. In 795 patients with thrombosis, LA was detectable in 6.03 per cent. The sensitivity of diluted activated partial thromboplastin time (dAPTT) and diluted Russell's viper venom time (dRVVT) alone, compared with the combination of the two was 83.3 per cent and 79.2 per cent respectively. Therefore, this new test scheme is a simple, inexpensive and efficient method for Thai patients.