Abstract Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r2>0.99 and presented intra- and interday precision within the range of 2.3 - 6.2 and 4.3 - 7.0%, respectively. Further intra- and interday accuracy was within the range of 88.2 - 105.8 and 90.6 - 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax =102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.

RESUMO Objetivo: Avaliar os resultados da vertebroplastia percutânea (VP) em fraturas por fragilidade da coluna (osteoporose/tumoral), analisando possíveis complicações. Método: Foram avaliados 33 pacientes com fratura da coluna vertebral (FXV) por osteoporose ou tumor, entre janeiro e novembro de 2021, submetidos à VP. Foi realizado exame físico junto à obtenção da história e fatores de risco para fragilidade óssea / tumor, além de avaliação radiológica da coluna para constatação de FXV. O método semiquantitativo de Genant foi empregado para a classificação no pós-operatório, além do score EVA e do questionário de incapacidade (ODI). O controle tomográfico foi avaliado por médico radiologista para quantificação do preenchimento vertebral e extravasamento, determinando para onde ocorreram. Resultados: Foram operadas 46 vértebras de 33 pacientes, como média de idade de 71 anos, sendo 11 pacientes com mais de um nível operado. Do total, 13 pacientes apresentavam fraturas tumorais e 20 possuíam fraturas por insuficiência. Observou-se extravasamento do PMMA em 31 vértebras, mais frequentemente para Plexo Venoso Vertebral Externo (23), Corpo Discal (9), Recesso Epidural Anterior (4) Vasos Pulmonares (4), Plexo Venoso Vertebral Interno (3), Cava Inferior (2), Plano Adiposo (2) e Veia Ázigos (1). Nenhum paciente apresentou complicações clínicas. Ainda, o EVA pré-operatório médio foi 8 e o pós-operatório de 3, enquanto o ODI pré-operatório médio foi de 56 e o pós-operatório de 30. Conclusão: O extravasamento de PMMA foi frequente em diversos locais e níveis, sem nenhuma complicação clínica. A VP mostrou-se eficaz na melhora de dor e função. Nível III; Estudo Longitudinal Coorte Retrospectivo.

ABSTRACT Objective: To evaluate the results of percutaneous vertebroplasty (PV) in spinal fragility fractures (osteoporosis/tumor), analyzing possible complications. Method: We evaluated 33 patients with spinal fractures (FXV) due to osteoporosis or tumor who underwent PV between January and November 2021. A physical examination was performed, obtaining the history and risk factors for bone fragility/tumor and a radiological evaluation of the spine to verify FXV. Genant’s semiquantitative method was used for postoperative classification, the VAS score, and a disability questionnaire (ODI). A radiologist evaluated tomographic control to quantify vertebral filling and extravasation, determining where they occurred. Results: 46 vertebrae of 33 patients were operated on, with a mean age of 71 years, and 11 patients with more than one level of surgery. Of the total, 13 patients had tumor fractures, and 20 had fractures due to insufficiency. PMMA extravasation was observed in 31 vertebrae, most frequently in the External Vertebral Venous Plexus (23), Discal Body (9), Anterior Epidural Recess (4), Pulmonary Vessels (4), Internal Vertebral Venous Plexus (3), Inferior Cava (2), Adipose Plane (2) and Azygos Vein (1). No patient had clinical complications. Furthermore, the mean preoperative VAS was eight, the postoperative one was 3, the mean preoperative ODI was 56, and the postoperative one was 30. Conclusion: PMMA extravasation was frequent in several locations and levels without any clinical complications. VP proved to be effective in improving pain and function. Level III; Longitudinal Retrospective Cohort Study.

RESUMEN Objetivo: Evaluar los resultados de la vertebroplastia percutánea (PV) en fracturas por fragilidad de columna (osteoporosis/tumor), analizando posibles complicaciones. Método: Se evaluaron 33 pacientes con fractura de columna (FXV) por osteoporosis o tumor, entre enero y noviembre de 2021, que fueron sometidos a PV. Se realizó examen físico junto con obtención de antecedentes y factores de riesgo de fragilidad ósea/tumor, además de evaluación radiológica de columna para verificar FXV. Para la clasificación postoperatoria se utilizó el método semicuantitativo de Genant, además de utilizar la escala EVA y un cuestionario de discapacidad (ODI). El control tomográfico fue evaluado por un radiólogo para cuantificar el llenado vertebral y la extravasación, determinando dónde se producían. Resultados: Se operaron 46 vértebras de 33 pacientes, con una edad promedio de 71 años, 11 pacientes con más de un nivel de cirugía. Del total, 13 pacientes presentaron fracturas tumorales y 20 fracturas por insuficiencia. Se observó extravasación de PMMA en 31 vértebras, con mayor frecuencia en el Plexo Venoso Vertebral Externo (23), Cuerpo Discal (9), Receso Epidural Anterior (4), Vasos Pulmonares (4), Plexo Venoso Vertebral Interno (3), Cava Inferior (2), Plano Adiposo (2) y Vena Azygos (1). Ningún paciente presentó complicaciones clínicas. Además, la EVA preoperatoria media fue de 8 y la postoperatoria de 3, mientras que la ODI preoperatoria media fue de 56 y la postoperatoria de 30. Conclusión: La extravasación de PMMA fue frecuente en varias localizaciones y niveles, sin complicaciones clínicas. VP demostró ser eficaz para mejorar el dolor y la función. Nivel III; Estudio de cohorte retrospectivo longitudinal.

RESUMO Objetivo Avaliar o deslocamento das estruturas nervosas conforme o decúbito do paciente em um estudo de Ressonância Nuclear Magnética (RNM). Métodos Foram realizadas RNM em 20 pacientes em uma clínica de radiologia em decúbito dorsal e lateral direito. A medida considerada será a menor distância entre a dura-máter e a parede medial do pedículo. Resultados A maior medida em decúbito lateral esquerdo foi 11,6 mm, em decúbito lateral direito foi 12,2 mm, em decúbito dorsal direito foi 10,5 mm e no esquerdo, 9,2 mm. O espaço entre a parede medial do pedículo é maior em decúbito lateral em alguns pacientes e, em outros, em decúbito dorsal. O deslocamento médio das medidas à esquerda foi 1,14 mm e à direita 1,355 mm. Conclusões As estruturas se deslocaram, em média, pouco mais de 1 mm nas posições estudadas. O posicionamento do paciente na cirurgia não muda o espaço a ser abordado, sendo de escolha do cirurgião, conforme a sua curva de aprendizado. Nível de evidência II; Estudo prospectivo de menor qualidade .

ABSTRACT Objective To evaluate the displacement of nerve structures according to the decubitus position of the patient in a magnetic resonance imaging (MRI) study. Methods MRI was performed at a radiology clinic in 20 patients in dorsal and right lateral decubitus. The measurement considered was the shortest distance between the dura mater and the medial wall of the pedicle. Results The largest measurement was 11.6 mm in left lateral decubitus, 12.2 mm in right lateral decubitus, 10.5 mm in right dorsal decubitus, and 9.2 mm in left dorsal decubitus. In some patients the space between the medial wall of the pedicle and the dura mater was larger when in lateral decubitus, while in others when in dorsal decubitus. The mean displacement of the measurements on the left was 1.14 mm and on the right 1.355 mm. Conclusions The structures moved on average little more than 1 mm in the positions studied. The positioning of the patient for surgery does not change the space to be approached, being the surgeon’s choice according to his learning curve. Level of evidence II; Prospective study of lower quality.

RESUMEN Objetivo Evaluar el desplazamiento de las estructuras nerviosas conforme al decúbito del paciente en un estudio de Resonancia Nuclear Magnética (RNM). Métodos Fueron realizadas RNM en 20 pacientes en una clínica de radiología en decúbito dorsal y lateral derecho. La medida considerada será la menor distancia entre la duramadre y la pared medial del pedículo. Resultados La mayor medida en decúbito lateral izquierdo fue 11,6 mm, en decúbito lateral derecho fue 12,2 mm, en decúbito dorsal derecho fue 10,5 mm y en el izquierdo, 9,2 mm. El espacio entre la pared medial del pedículo es mayor en decúbito lateral en algunos pacientes y, en otros, en decúbito dorsal. El desplazamiento promedio de las medidas a la izquierda fue 1,14 mm y a la derecha de 1,355 mm. Conclusiones Las estructuras se desplazaron, en promedio, poco más de 1 mm en las posiciones estudiadas. El posicionamiento del paciente en la cirugía no cambia el espacio a ser abordado, siendo la elección del cirujano conforme a su curva de aprendizaje. Nivel de evidencia II; Estudio prospectivo de menor calidad.

ABSTRACT Setting: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. Objective: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. Design: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. Results: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. Conclusion: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

OBJETIVO: Testes-desafio desenvolvidos para avaliar as vias serotoninérgicas utilizaram amplamente citalopram intravenoso. Citalopram oral também foi utilizado, mas obtiveram-se resultados insatisfatórios com uma dose de 20 mg. O objetivo deste estudo foi o de determinar se uma dose oral mais elevada poderia reproduzir resultados similares aos descritos para administração intravenosa. Com esta finalidade, avaliamos os níveis de cortisol, de hormônio do crescimento e de prolactina. MÉTODO: Oito voluntários do sexo masculino saudáveis foram avaliados em um teste-desafio cruzado, aleatorizado, com 40 mg de citalopram oral ou placebo. RESULTADOS: Os níveis de cortisol aumentaram após 2-4 horas da ingestão de citalopram oral, com um pequeno pico de amplitude ocorrendo em dois terços dos indivíduos. Os níveis de prolactina e de hormônio de crescimento permaneceram inalterados ao longo do estudo. CONCLUSÃO: O uso de citalopram oral poderia apresentar uma alternativa em testes-desafio serotoninérgicos, mas doses maiores são necessárias.

OBJECTIVE: Challenge tests designed to evaluate serotoninergic pathways have widely used intravenous citalopram. Oral citalopram has also been used, but unsatisfactory results were obtained with a dose of 20 mg. The objective of this study was to determine whether a higher oral dose would reproduce similar to those described for intravenous administration. To that end, we evaluated cortisol, growth hormone and prolactin levels. METHOD: Eight healthy male volunteers were evaluated in a randomized crossover challenge test with 40 mg of oral citalopram or placebo. RESULTS: Cortisol levels increased at 2-4h after the oral citalopram intake, with a small amplitude peak occurring in two-thirds of the subjects. Levels of prolactin and growth hormone remained unchanged throughout the study. CONCLUSION: The use of oral citalopram might present an alternative in serotoninergic challenge tests, but higher doses are required.

As lagartas de Deuterollyta majuscula (Herrich-Schaffer) podem, ao se alimentar, causar danos às folhas e frutos do abacateiro. O objetivo deste trabalho foi estudar a biologia em condições de laboratório, mantido a 25±2ºC, UR de 70±10% e fotofase de 14 horas e descrever os danos provocados pela praga. O ciclo biológico (ovo-adulto) foi de 39,6 dias e a viabilidade total de 55%. Foram determinados 5 instares. O peso de pupas foi de 0,0966 mg para fêmeas e 0,0901 mg para os machos. As fêmeas colocaram, em média, 201 ovos durante aproximadamente 7,6 dias. A longevidade média de machos e fêmeas foi de 15,3 e 13,9 dias, respectivamente, e a razão sexual de 0,56. Através da tabela de vida de fertilidade determinou-se uma capacidade de aumento de 64 vezes a cada geração, sendo a duração média de uma geração de 46 dias e a razão finita de aumento (<FONT FACE=Symbol>ll</FONT>) de 1,095. Estes resultados fornecem subsídios que podem ser utilizados para o estabelecimento de estratégias de manejo do inseto.

Deuterollyta majuscula (Herrich-Schaffer) causes injuries to leaves and fruits of avocado. The aim of this work was study the biology under laboratory conditions, at 25±2ºC, 70±10% of RH, and 14-hour of photophase and to describe the damage caused by this pest. The biological cycle (egg-adult) was 39.6 days and the total viability was 55%. Five instars were observed. The pupae weight was 0.0966 mg for females and 0.0901 mg for males. The females laid an average of 201 eggs in approximately 7.6 days. The mean longevity of males and females was 15.3 and 13.9 days, respectively, and sex ratio of 0.56. The fertility life table showed a 64-fold increase capacity in each generation, with one generation lasting an average of 46 days, with finite rate of increase (lambdal) of 1.095. These results can provide background information to the establishment of strategies to manage this new avocado pest.