Fatores associados à adesão a terapia imunossupressora em indivíduos transplantados renais / Factors associated with adherence to immunosuppressive therapy in renal transplant recipients / Factores asociados a la adherencia a la terapia inmunosupresora en receptores de trasplante renal

Objetivo: Analisar os fatores associados à adesão a terapia imunossupressora em indivíduos transplantados renais. Métodos: Trata-se de estudo de corte transversal, com indivíduos transplantados renais em acompanhamento ambulatorial, na cidade do Recife, Nordeste do Brasil. Utilizou-se a Assessment of Adherence with Immunosuppressive Medication Scale para avaliar a adesão aos imunossupressores. Resultados: Em 147 transplantados renais, foi observada uma prevalência de mulheres (51,70%) com baixa escolaridade e baixo nível socioeconômico (60,54%). A amostra foi composta, em sua maioria, por receptores de enxerto renal proveniente de doador cadáver (50,34%), com tempo de espera para o transplante de até 48 meses (62,59%). A taxa de adesão dos participantes foi de 56,42%, e esteve associada ao tempo médio pós-transplante (p=0,033), com maior índice naqueles com menos de 5 anos de transplante renal. Os fatores associados a não adesão foram atrasos e esquecimentos. Conclusão: Considerando a necessidade de ampliar a taxa de adesão, é fundamental considerar o tempo de transplante renal no planejamento das ações. Além disso, é preciso utilizar estratégias que auxiliem na manutenção da tomada dos imunossupressores conforme prescrição médica a fim de contribuir para a manutenção do enxerto renal. (AU)

Objective: To analyze the factors associated with adherence to immunosuppressive therapy in kidney transplant patients. Methods: This is a cross-sectional study, with kidney transplant patients undergoing outpatient follow-up, in the city of Recife, Northeast Brazil. The Assessment of Adherence with Immunosuppressive Medication Scale was used to assess adherence to immunosuppressants. Results: In 147 kidney transplant recipients, there was a prevalence of women (51,70%), with low education and low socioeconomic status (60,54%). The sample consisted, mostly, of kidney graft recipients from cadaver donors (50,34%), with a waiting time for transplantation of up to 48 months (62,59%). The adherence rate of the participants was 56.42%, and was associated with the average post-transplant time (p = 0.033), with a higher rate in those with less than 5 years of kidney transplantation. The factors associated with non-adherence were delays and forgetfulness. Conclusion: Considering the need to increase the adherence rate, it is essential to consider the time of kidney transplantation when planning actions. In addition, it is necessary to use strategies that assist in maintaining the intake of immunosuppressants according to medical prescription in order to contribute to the maintenance of the renal graft. (AU)

Objetivo: Analizar los factores asociados a la adherencia a la terapia inmunosupresora en receptores de trasplante renal. Métodos: Se trata de un estudio transversal con pacientes con trasplante renal en seguimiento ambulatorio, en la ciudad de Recife, noreste de Brasil. Se utilizó la Assessment of Adherence with Immunosuppressive Medication Scale para evaluar la adherencia a los inmunosupresores. Resultados: En 147 receptores de trasplante renal, hubo una prevalencia de mujeres (51,70%), con bajo nivel educativo y nivel socioeconómico bajo (60,54%). La muestra estuvo compuesta, mayoritariamente, por receptores de injerto renal de donante cadáver (50,34%), con un tiempo de espera para el trasplante de hasta 48 meses (62,59%). La tasa de adherencia de los participantes fue del 56,42% y se asoció con el tiempo medio pos trasplante (p = 0,033), con una tasa mayor en aquellos con menos de 5 años de trasplante renal. Los factores asociados a la no adherencia fueron los retrasos y el olvido. Conclusión: Considerando la necesidad de incrementar la tasa de adherencia, es fundamental considerar el momento del trasplante renal a la hora de planificar acciones. Además, es necesario utilizar estrategias que ayuden a mantener la ingesta de inmunosupresores según prescripción médica para contribuir al mantenimiento del injerto renal. (AU)

A new species of the Goblin Spider genus Predatoroonops/ Brescovit, Rheims amp; Ott 2012 (Araneae, Dysderoidea: Oonopidae), with new records for the genus.

The family Oonopidae Simon, 1890 is composed of tiny spiders between 0.5 and 4mm (Baehr et al. 2012) that are distributed all over the world (Platnick et al. 2020; World Spider Catalog 2021). They occupy diverse habitats, mainly in tropical and subtropical regions (Platnick et al. 2020), generally associated with the soil and litter fauna (Ranasinghe Benjamin 2018). Oonopidae is among the eight most diverse spider families with 114 genera and 1872 species (World Spider Catalog 2021). Most of this diversity was discovered after 2006, as a result of the Planetary Biodiversity Inventory (PBI) project: Goblin Spider (Platnick et al. 2012). Recent molecular phylogenetic analyses recovered Oonopidae as monophyletic (Wheeler et al. 2017), hypothesis supported by the presence of a synapomorphic pair of completely fused testicles (Burger Michalik 2010). Brazil has a great diversity of Oonopidae (e.g., Brescovit et al. 2012a; Platnick et al. 2013; Feitosa et al. 2017), including the genus Predatoroonops Brescovit, Rheims Ott 2012, endemic to the Atlantic Forest, that includes 17 species (World Spider Catalog 2021). The genus can be recognized by the male chelicerae frontally modified, with one or two pairs of distally sclerotized, and sometimes branched, apophyses, and by the pars cephalica dorsally squared (Brescovit et al. 2012b). In this paper, we describe a new species of the genus, based on a male specimen from the State of Minas Gerais: Predatoroonops stani sp. nov.. Also, we give new records for Predatoroonops yautja Brescovit, Rheims Santos, 2012 from the same state and a distribution map with all the records of Predatoroonops along the Atlantic Forest.

Description of a new Neotropical spider genus in the family Ctenidae Keyserling, 1877 (Araneae: Lycosoidea) from the Brazilian Amazon rainforest.

A new Neotropical genus of Ctenidae from the Brazilian Amazon rainforest is described based on male and female characters: Bulboctenus gen. nov. Three new species are described for the genus: Bulboctenus kayapo sp. nov., Bulboctenus itunaitata sp. nov. and Bulboctenus munduruku sp. nov. The genus can be distinguished from other Ctenidae by males with median apophysis oriented horizontally, perpendicular to the tegulum, RTA strongly excavated anteriorly, metatarsi III and IV with bulbous setae ventrally, sternum and coxae with thick setae; and females with median sector of the epigyne hexagonal with two posterior conical projections ventrally and elevated lateral margins. Discussion on the modification on the leg setae across the Neotropical Ctenids species are given.

Effect of Lercanidipine on the Pharmacokinetics-Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease.

This study evaluates the carvedilol-lercanidipine drug interaction, and the influence of chronic kidney disease (CKD) on both drugs. Patients with high blood pressure (8 with normal renal function [control] and 8 with CKD with estimated glomerular filtration rate categories of G3b to G5 [12-38 mL/min/1.73 m2 ]) were included and prescribed 3 different treatment regimens, a single oral dose of racemic carvedilol 25 mg (CAR), a single oral dose of racemic lercanidipine 20 mg (LER), and single oral doses of CAR plus LER. Blood samples were collected and variations in heart rate were assessed (using isometric exercise with handgrip) for up to 32 hours. Lercanidipine pharmacokinetics were not enantioselective, and were not affected by carvedilol and CKD. Carvedilol pharmacokinetics (data presented as median) were enantioselective with higher plasma exposure of (R)-(+)-carvedilol in both control (103.5 vs 46.0 ng ∙ h/mL) and CKD (190.6 vs 98.9 ng ∙ h/mL) groups. Lercanidipine increased the area under the plasma concentration-time curve of only (R)-(+)-carvedilol in the CKD group (190.6 vs 242.2 ng ∙ h/mL) but not in the control group (103.5 vs 98.7 ng ∙ h/mL). CKD increased plasma exposure (46.0 vs 98.9 ng ∙ h/mL) and effect-compartment exposure (5.5 vs 20.9 ng ∙ h/mL) to (S)-(-)-carvedilol, resulting in higher ß-adrenergic inhibition (10.0 vs 6.1 bpm). Therefore, carvedilol dose titration in CKD patients with estimated glomerular filtration rate categories of G3b to G5 should be initiated, with no more than half the dose used for patients with normal renal function.

Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats.

Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry.

A sensitive and selective method for the analysis of ibuprofen enantiomers by LC-MS/MS was developed and validated for the purpose of application in pharmacokinetic studies in small experimental animals. Aliquots of 200 µL plasma were submitted to liquid-liquid extraction with hexane/diisopropylether (50:50 v/v) in acid pH. Separation was accomplished in a Chirex® 3005 (250 × 4.6 mm, 5 µm) column at 25°C with a mobile phase that consisted of 0.01 M ammonium acetate in methanol at a flow rate of 1.1 mL/min. The mass spectrometer consisted of an ESI interface operating at negative ionization mode and multiple reaction monitoring. The transitions 205 > 161 and 240 > 197 were monitored for ibuprofen enantiomers and fenoprofen (internal standard), respectively. Method validation included the evaluation of the matrix effect, stability, linearity, lower LOQ, within-run and between-run precision, and accuracy. The lower LOQ was 25 ng/mL for each ibuprofen enantiomer, and the calibration curves showed good linearity in the range 0.025-50 µg/mL. The method was successfully applied in the investigation of pharmacokinetic disposition of ibuprofen enantiomers in rats treated orally with 25 mg/kg of the racemate. Enantioselective kinetic disposition was observed with accumulation of (+)-(S)-ibuprofen in rats following single oral administration.

Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%).

Determination of cyclophosphamide enantiomers in plasma by LC-MS/MS: Application to pharmacokinetics in breast cancer and lupus nephritis patients.

This article describes the enantioselective analysis of cyclophosphamide (CPA) in human plasma using LC-MS/MS. CPA enantiomers were extracted from plasma using a mixture of ethyl acetate and chloroform (75:25, v/v). The enantiomers were separated on a Chiralcel(R) OD-R column, with the mobile phase consisting of a mixture of acetonitrile and water (75:25, v/v) plus 0.2% formic acid. The protonated ions and their respective product ions were monitored using two functions, 261 > 141 for CPA enantiomers and 189 > 104 for the internal standard (antipyrine). Recovery rates were higher than 95% and the quantification limit was 2.5-ng/ml plasma for both enantiomers. The coefficients of variation and the relative errors obtained for the validation of intra- and interassay precision and accuracy were less than 10%. The method was applied for the investigation of the enantioselective pharmacokinetics of CPA in a lupus nephritis patient treated with 1 g CPA infused over 2 h and in a breast cancer patient treated with 0.9 g infused over 1 h. No stereoselectivity in the pharmacokinetic parameters was observed for either patient. Clearance values of 2.63 and 2.93 l/h and of 3.36 and 3.61 l/h for (-)-(S) and (+)-(R)-CPA were obtained for the breast cancer and lupus nephritis patient, respectively.

Enantiosseletividade na disposição cinética da nisoldipina em pacientes hipertensos portadores de Diabetes mellitus tipo 2. Utilização da lidocaína como fármaco marcador do CYP3A4 / Enantioselective kinetic disposition of nisoldipine in hypertensive patients presenting with type 2 Diabetes mellitus. Lidocaine used as a marker drug of CYP3A4

A nisoldipina é um antagonista de cálcio da classe das di-hidropiridinas disponível na clínica como mistura racêmica para o tratamento da hipertensão. No presente estudo foi investigada a influência do diabetes mellitus tipo 2 (DM) sobre a farmacocinética enantiosseletiva e nos parâmetros farmacodinâmicos da nisoldipina. Dezessete pacientes hipertensos, sendo nove portadores de diabetes mellitus foram investigados depois da administração da nisoldipina racêmica na forma de comprimidos de liberação controlada (20mg/dia) ou placebo por 15 dias. As amostras seriadas de sangue (0-24h) foram colhida no 15º dia, e medidas de pressão arterial por 24h foram simultaneamente avaliadas...

Diabetes: análise global na Unidade Básica de Saúde Bandeirantes-Londrina-PR / Diabetes: a global analysis in the Bandeirantes's Health Basic Unit -Londrina-PR

O trabalho analisa uma amostra de 32 diabéticos, pareados em sexo e idade, acima de 30 anos, com 32 näo-diabéticos, ambos frequentadores da Unidade Básica de Saúde Bndeirantes. O objetivo é verificar o perfil do diabético, conhecimento sobre a doença e observar se a frequência da doença na família dos diabéticos é maior do que na família de näo-portadores. Constatou-se que a prevalência de diabéticos é maior no sexo feminino, casado, com 1§ grau incompleto, do lar, do lar, raça branca e o diabetes é do tipo II (näo-insulino-dependente). Em relaçäo ao tratamento, 63,3 por cento têm dificuldades em adquirir a medicaçäo para uso diário e 59,3 por cento dos diabéticos entrevistados näo seguem a dieta necessária. O diabético faz menos exercícios que a populaçäo geral, desconhecendo o fato de que a falta de exercício é agravante da doença, o mesmo ocorrendo com o alccolismo, tabagismo, estresse, peso acima do normal e dieta irregular. O diabético tem mais informaçöes sobre os sintomas e as complicaçöes da doença em relaçäo ao controle. Os consanguíneos em 1§ grau dos diabéticos têm maior frequência de diabetes do que os familiares em 1§ grau dos näo-diabéticos. Estes estudos foram estatisticamente significativos

Variaçäo circadiana no infarto agudo do miocardio / Circadian variation in the acute myocardial infarction

O aparecimento dos sintomas do infarto agudo do miocardio foi estudado em 49 pacientes em relaçäo a hora do dia e ao tempo após despertar. A maioria dos pacientes estudados (31) acordou entre 5 e 7 horas. Analisando o horário de aparecimento dos sintomas nas 24 horas, näo se observou predominio dos sintomas em nenhum horário específico. Quando se relaciona o início dos sintomas com o despertar, verificou-se um pico principalmente na primeira hora e picos menores por volta de 3 e 7 horas após os pacientes acordarem. Assim, parece que ao despertar, graças a interaçöes hormonais e humorais, a incidência de infarto está aumentada, näo constituindo é claro este um fator isolado no desencadear dos sintomas do evento agudo.