Mortality and years of life lost related to adverse drug events in Brazil.

OBJECTIVE: To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS: This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS: For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS: The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

Mortality and years of life lost related to adverse drug events in Brazil

ABSTRACT OBJECTIVE To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

Hospitalizations and adverse drug events in the Brazilian unified health system: a ten-year retrospective analysis of routine data.

OBJECTIVE: To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS: Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS: Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS: The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.

Hospitalizations and deaths related to adverse drug events worldwide: Systematic review of studies with national coverage.

PURPOSE: Adverse drug events are related to negative outcomes in healthcare, including hospitalization, increased duration of hospital stay and death. The aim of this study was to conduct a systematic review to evaluate hospitalizations and deaths related to adverse drug events worldwide, reported in studies with national coverage. METHODS: The protocol was registered in PROSPERO (CRD42020157008). We performed a systematic search on Medline, Embase, CINAHL, LILACS, and the Cochrane Library (until March 2020) using pre-specified terms. We included published studies that reported data on hospitalizations and/or deaths related to adverse drug events from a national perspective and the use of secondary data as a source of information. Two reviewers independently extracted and synthesized data. The quality of the studies was assessed using an adapted version of the Joanna Briggs Institute critical appraisal checklist for prevalence studies. Narrative summaries of findings were undertaken. RESULTS: Among 59,336 citations, 62 studies were included for data extraction and synthesis. Among these studies, 41 studies included the outcome of hospitalization, 16 included the death outcome, and five included both outcomes. Administrative databases regarding discharges and registries of vital statistics were the most common sources of information. The relative frequency of hospitalizations ranged from 0.03% to 7.3%, and from 9.7 to 383.0/100,000 population, whereas mortality rate ranged from 0.1 to 7.88/100,000 population. CONCLUSION: Our study highlights information about adverse drug events using large administrative databases in a national scenario and provides an overview of databases and methods implemented to detect adverse drug events.

Hospitalizations and adverse drug events in the Brazilian unified health system: a ten-year retrospective analysis of routine data

ABSTRACT OBJECTIVE To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.

Development and Optimization of Solanum Lycocarpum Polyphenol Oxidase-Based Biosensor and Application towards Paracetamol Detection.

Purpose: The development biosensing technologies capable of delivering fast and reliable analysis is a growing trend in drug quality control. Considering the emerging use of plant-based polyphenol oxidases (PPO) as biological component of electrochemical biosensors, this work reports the first Solanum lycocarpum PPO biosensor and its use in the pharmaceutical analysis of paracetamol in tablet formulations. Methods: The biosensor was optimized regarding fruit maturation (immature and mature-ripe), vegetal extract volume to be used in biosensor construction as well as optimal pH of electrochemical cell fluid. Results: Results evidenced that the extract which rendered the biosensor with best analytical performance was from immature fruits, and the biosensor produced using 100 µL of crude plant extract promoted better faradaic signal gathering. Moreover, when neutral pH media was used in the electrochemical cell, the biosensor showcased best faradaic signal output from the used redox probe (catechol), suggesting thence that the method presents high sensibility for phenolic compounds detection. Furthermore, the biosensor was able to quantify paracetamol in a linear range from 50 to 300 µM, showcasing LoD and LoQ of 3 µM and 10 µM, respectively. Conclusion: after careful evaluation, this biosensor might be a low-cost alternative for conventional pharmaceutical quality control methods.

Characterization of adverse drug events identified by trigger in Brazilian pediatric inpatients.

OBJECTIVE: To describe the frequency and characteristics of adverse drug events in pediatric inpatients in a Brazilian tertiary teaching hospital. METHODS: A cross-sectional study was conducted by retrospective and manual chart review of 240 pediatric admissions to identify adverse drug events using 17 triggers. When triggers were detected in the chart, reviewers investigated the chart in depth to decide whether an event occurred. Consensus about the occurrence of the event was obtained in meeting with a healthcare team. Events were classified by harm category and drugs were classified according to the Anatomical Therapeutic Chemical Classification. Patients who had suffered were compared to those who had not experienced events using the chi-squared test and the Mann-Whitney U test. RESULTS: A total of 62 adverse events were found, and 18.8% of the patients had at least one event. Adverse events rates were 25.83 per 100 admissions, 20.27 per 1000 patient-days, 25.94 per 1000 drugs, and 2.12 per 1000 drug doses. All events found were classified as temporary harm, and cardiovascular drugs were most frequently related to events. Groups of patients with and without event were segregated (p<0.05) by the length of stay, number of drugs, and drug doses. CONCLUSION: The use of triggers demonstrated its utility in a pediatric setting by identifying harm. Adverse events rates were found to be higher than those of previous studies, but the harm rate was lower than other studies. This study enables the measurement of adverse events in order to define strategies to mitigate or reduce harm.

Medicamentos potencialmente inapropriados prescritos a pacientes de um Centro de Referência em Atenção à Saúde da Pessoa Idosa / Potentially inappropriate medications prescribed to patients at the Reference Center in Health Care for Old People

Resumo Objetivo Analisar o perfil farmacoterapêutico dos idosos atendidos em um Centro de Referência em Atenção à Saúde da Pessoa Idosa quanto ao uso de medicamentos potencialmente inapropriados (MPI) por meio de três critérios de rastreamento e determinar fatores associados à prescrição de MPI. Método Estudo transversal com dados obtidos por revisão retrospectiva dos prontuários de idosos, atendidos entre 2017 e 2018 por médico geriatra. Para identificar os MPI, utilizaram-se os Critérios de Beers, o Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) e o Consenso Brasileiro de Medicamentos Potencialmente Inapropriados para Idosos. Características relacionadas ao perfil sociodemográfico (idade e sexo), de hábitos de vida (tabagismo e consumo de álcool), clínico (doenças) e farmacoterapêutico (medicamentos e Índice de Complexidade da Farmacoterapia - ICFT) foram avaliadas. Resultados Foram analisados 406 prontuários e identificados 3.059 medicamentos prescritos, dos quais 32,1% são MPI segundo Critérios STOPP, 14,4% pelo Consenso Brasileiro e 11,7% pelos Critérios de Beers. No total, 81,1% dos idosos apresentaram ao menos um MPI. Regressão de Poisson demonstrou associação entre a prescrição de MPI com polifarmácia, maior número de sinais e sintomas e maior valor de ICFT em ao menos um dos critérios. A força de concordância entre os critérios de MPI foi moderada. Conclusões A maioria dos prontuários analisados possuíam ao menos um MPI prescrito, sendo que os Critérios STOPP identificaram uma maior quantidade de MPI. Estratégias devem ser implementadas para melhorar a farmacoterapia dos idosos com atenção para os que apresentam fatores associados a MPI em seu perfil.

Abstract Objective To analyze the pharmacotherapeutic profile of the old people assisted at a Reference Center in Health Care for Old People regarding the use of potentially inappropriate medications (PIM) using three screening criteria and to determine factors associated with the prescription of PIM. Method Cross-sectional study with data obtained by retrospective review of the medical records of the old people, attended between 2017 and 2018 by a geriatric doctor. To identify the PIM, the Beers Criteria, the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) and the Brazilian Consensus on Potentially Inappropriate Medications for Old People were used. Characteristics related to the sociodemographic profile (age and sex), lifestyle (smoking and alcohol consumption), clinical (diseases) and pharmacotherapeutic (medications and Medication Regimen Complexity Index - MRCI) were evaluated. Results 406 medical records were analyzed and 3,059 prescription medications were identified, of which 32.1% are PIM according to STOPP Criteria, 14.4% by the Brazilian Consensus and 11.7% by the Beers Criteria. In total, 81.1% of the old people had at least one PIM. Poisson regression demonstrated an association between the prescription of PIM with polypharmacy, a greater number of signs and symptoms and a higher MRCI value in at least one of the criteria. The strength of agreement between the PIM criteria was moderate. Conclusions Most of the analyzed medical records had at least one prescribed PIM, and the STOPP Criteria identified a greater amount of PIM. Strategies must be implemented to improve the pharmacotherapy of old people with attention to those who have factors associated with PIM in their profile.

A simulação no ensino de competências para a realização de serviços farmacêuticos de âmbito clínico / Use of simulation in teaching competencies for pharmaceutical clinical services

O cuidado farmacêutico, operacionalizado em serviços farmacêuticos de âmbito clínico, é capaz de aumentar os desfechos desejáveis a partir do uso dos medicamentos. A realização destes depende de competências clínicas adequadas, cujo desenvolvimento ocorre por meio de métodos que permitam ao estudante a associação entre conhecimentos, habilidades e atitudes. A simulação é um método que proporciona um cenário adequado para esse fim e, por isso, buscou-se analisar e reunir evidências sobre seu uso no desenvolvimento de competências para a realização desses serviços por meio de uma revisão integrativa. A intersecção entre os descritores "cuidados farmacêuticos" e "competências clínicas" nos bancos de dados PubMed/MedLine e Lilacs, entre os anos de 2013 e 2018, retornou 703 estudos, dos quais 18 foram incluídos por dois pesquisadores independentes. Como resultados, 61,1% dos estudos utilizaram a simulação para desenvolvimento e avaliação da comunicação com paciente e equipe de saúde, 50,0% dos estudos avaliou o componente "habilidade" e a simulação realística ou virtual foi utilizada em 55,5% dos estudos. A simulação demonstra ser um método pertinente ao desenvolvimento de competências clínicas, porém seu uso no Brasil se mostra incipiente e os recursos de infraestrutura e econômicos são os principais obstáculos para seu o uso.(AU)

Pharmaceutical care in pharmaceutical clinical services is able to increase the desired outcomes through the use of medications. The performance of these services depends on appropriate clinical competence, whose development is related to the appropriate choice of a method that allows the student to associate knowledge, skills and attitudes. Simulation is a method that provides an adequate setting for this purpose and, therefore, we sought to analyze and gather evidence on its use for developing competence to perform pharmaceutical clinical services through an integrative review. The intersection between the keywords "pharmaceutical services" and "clinical competence" in the PubMed/ MedLine and Lilacs databases between 2013 and 2018 yielded 703 studies, and 18 of those studies were included by two independent researchers. As results, 61.1% of the studies used simulation to develop and evaluate communication with patient and health team, 50.0% of the studies evaluated the component "skill" and 55.5% of the studies used realistic or virtual simulation. Simulation proves to be a relevant method for the development of clinical competence in pharmaceutical services, but its use in Brazil is incipient and infrastructure and economic resources are the main obstacles to its use.(AU)

Determination of Methyldopa and Paracetamol in Pharmaceutical Samples by a Low Cost Genipa americana L. Polyphenol Oxidase Based Biosensor.

Purpose: Jenipapo fruit (Genipa americana L) is a natural source of polyphenol oxidases (PPOs) whose potential in pharmaceutical analysis is noteworthy. Henceforth, this work reports the electrochemical study of a low-cost PPO-based biosensor produced from the crude extract of Jenipapo fruits and accounts a practical approach to employ this biosensor in the determination of methyldopa and paracetamol in pharmaceutical samples. Methods: In order to investigate the electrochemical properties of the biosensor, theoretical and practical approaches were employed, and both samples and the biosensor were analyzed through electrochemical impedance spectroscopy (EIS) and voltammetric techniques, namely: differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Results: showcased that the biosensor presented good analytical features, as well as low detection limits (8 µmol L-1 for methyldopa and 5 µmol L-1 for paracetamol). The relative standard deviation was less than 5% mid-assay. Conclusion: The use of this biosensor is a reliable, low cost and useful alternative in the pharmaceutic determination of phenolic drugs (e.g. methyldopa and paracetamol).

The Brazilian Portuguese version of the Pediatric Trigger Toolkit is applicable to measure the occurrence of adverse drug events in Brazilian pediatric inpatients / A versão em Português-BR do Pediatric Trigger Toolkit é aplicável para mensurar eventos adversos a medicamentos em pacientes pediátricos internados em hospitais brasileiros

Abstract Objective: To describe the process of translation, adaptation, and validation of the Brazilian Portuguese version of the Pediatric Trigger Toolkit: Measuring Adverse Drug Events in the Children's Hospital. Methods: The validation process for the research instrument was carried out in five steps: (I) translation from English into Brazilian Portuguese by two independent translators; (II) synthesis of the translated versions; (III) adaptation of the triggers to the Brazilian context using a modified Delphi method carried out in two rounds; (IV) application of the research instrument in the review of 240 hospitalizations during 2014; and (V) back-translation from Brazilian Portuguese to English. Results: The translation step resulted in two versions, which were then synthesized to obtain equivalence within the Brazilian cultural context. The process of adapting the research instrument allowed the inclusion and adaptation of some triggers, as well as the exclusion of others, based on the consensus reached among experts during the Delphi step. The positive predictive value of the research instrument was 13.51%, and the antihistamine trigger presented the highest positive predictive value. Conclusion: The research instrument can be used to track the occurrence of adverse drug events in pediatric patients in Brazilian hospitals. Despite the adjustments made, triggers that were not identified or that had low positive predictive value can suggest the need for additional changes. However, more studies are needed before modifying or removing a trigger.

Resumo Objetivo: Descrever o processo de tradução, adaptação e validação para o português do Pediatric Trigger Toolkit: Measuring Adverse Drug Events in the Children's Hospital. Métodos: O processo de validação do instrumento de pesquisa foi realizado em 5 etapas: (I) tradução do inglês para o português por dois tradutores independentes; (II) síntese das versões traduzidas; (III) adaptação dos rastreadores para realidade brasileira por meio do método Delphi modificado, em duas rodadas; (IV) aplicação do instrumento de pesquisa na revisão de 240 internações de 2014; e (V) retrotradução do português para o inglês. Resultados: A etapa de tradução resultou em duas versões traduzidas, que foram sintetizadas de forma a obter equivalência ao contexto cultural brasileiro. O processo de adaptação do instrumento de pesquisa possibilitou a inclusão e adaptação dos rastreadores, bem como a exclusão de rastreadores segundo consenso obtido entre os especialistas na etapa Delphi. O valor preditivo positivo do instrumento de pesquisa foi de 13,51% e o rastreador anti-histamínico foi o que apresentou maior valor preditivo positivo. Conclusão: O instrumento de pesquisa pode ser utilizado para rastrear a ocorrência de eventos adversos a medicamentos em pacientes pediátricos nos hospitais brasileiros. Apesar das adaptações realizadas, rastreadores que não foram identificados ou com baixo valor preditivo positivo podem indicar, ainda, a necessidade de modificações. Entretanto, mais estudos são necessários antes de modificar ou excluir algum rastreador.

The Brazilian Portuguese version of the Pediatric Trigger Toolkit is applicable to measure the occurrence of adverse drug events in Brazilian pediatric inpatients.

OBJECTIVE: To describe the process of translation, adaptation, and validation of the Brazilian Portuguese version of the Pediatric Trigger Toolkit: Measuring Adverse Drug Events in the Children's Hospital. METHODS: The validation process for the research instrument was carried out in five steps: (I) translation from English into Brazilian Portuguese by two independent translators; (II) synthesis of the translated versions; (III) adaptation of the triggers to the Brazilian context using a modified Delphi method carried out in two rounds; (IV) application of the research instrument in the review of 240 hospitalizations during 2014; and (V) back-translation from Brazilian Portuguese to English. RESULTS: The translation step resulted in two versions, which were then synthesized to obtain equivalence within the Brazilian cultural context. The process of adapting the research instrument allowed the inclusion and adaptation of some triggers, as well as the exclusion of others, based on the consensus reached among experts during the Delphi step. The positive predictive value of the research instrument was 13.51%, and the antihistamine trigger presented the highest positive predictive value. CONCLUSION: The research instrument can be used to track the occurrence of adverse drug events in pediatric patients in Brazilian hospitals. Despite the adjustments made, triggers that were not identified or that had low positive predictive value can suggest the need for additional changes. However, more studies are needed before modifying or removing a trigger.

Stability of immobilized laccase on Luffa Cylindrica fibers and assessment of synthetic hormone degradation.

In this work were studied the pH, thermal, and storage stability of free and immobilized laccases. Enzymes were produced by Pleurotus ostreatus on potato dextrose (PD) broth and potato dextrose modified (PDM) broth, and immobilized using Luffa cylindrica fibers as support. Both free and immobilized enzymes were assessed on their respective enzymatic activities and for 17α-ethinylestradiol (EE2) degradation. The optimum pH conditions concerning laccase activity ranged from 3.6 to 4.6, while temperature ranged between 30 °C and 50 °C for both free and immobilized enzyme. Laccase produced using PD broth presented greater storage stability and thermal stability than that of PDM. Best EE2 removals were of 79.22% and 75.00% for the free and immobilized enzymes, respectively. Removal rates were assessed during 8 h at pH 5. The removal of 17α-ethinylestradiol was stabilized in the fourth cycle of use. Results imply that immobilization promoted stability towards pH and temperature variations, although media played a decisive role in the enzymatic activity. Both free and immobilized laccases of P. ostreatus were able to degrade EE2, whereas immobilized laccase in PDM medium presented possible reuse applicability, albeit removal was not optimal when compared to other reports.

Impact of medication therapy management on pharmacotherapy safety in an intensive care unit.

Background Drug-related problems are mostly preventable or predictable circumstances that may impact on health outcomes. Clinical pharmacy activities such as medication therapy management can identify and solve these problems, with potential to improve medication safety and effectiveness. Objective To evaluate ability of medication therapy management service to detect drug-related problems and prevent adverse drug events. This study also aimed to assess the risk factors for drugrelated problem occurrence. Setting Medical intensive care unit of a public tertiary hospital in Brazil. Methods Patients were evaluated by a clinical pharmacist, who provided medication therapy management service. Detected drug-related problems were categorized according to the Pharmaceutical Care Network Europe methodology and analyzed in multinomial regression to identify risk factors. Main outcome measure Potential risk factors for drug-related problem occurrence. Results The proposed medication therapy management service allowed detection of 170 drug-related problems that had potential to reach patients causing harm and other 50 unavoidable adverse events. Drug-related problems identified were more often associated with antibacterial use, caused by improper combinations or inadequate drug dosage. These problems required interventions that were accepted by the multidisciplinary team, resulting in more than 85% adherence and total problem solving. Main risk factors identified were previous diagnosis of kidney injury (OR = 8.38), use of midazolam (OR = 7.96), furosemide (OR = 5.87) and vancomycin (OR = 4.82). Conclusion Medication therapy management proved to be an effective method not only for drug-related problem detection, but also for adverse drug event prevention, contributing to improve patient safety.

Development of a Polyphenol Oxidase Biosensor from Jenipapo Fruit Extract (Genipa americana L.) and Determination of Phenolic Compounds in Textile Industrial Effluents.

In this work, an innovative polyphenol oxidase biosensor was developed from Jenipapo (Genipa americana L.) fruit and used to assess phenolic compounds in industrial effluent samples obtained from a textile industry located in Jaraguá-GO, Brasil. The biosensor was prepared and optimized according to: the proportion of crude vegetal extract, pH and overall voltammetric parameters for differential pulse voltammetry. The calibration curve presented a linear interval from 10 to 310 µM (r² = 0.9982) and a limit of detection of 7 µM. Biosensor stability was evaluated throughout 15 days, and it exhibited 88.22% of the initial response. The amount of catechol standard recovered post analysis varied between 87.50% and 96.00%. Moreover, the biosensor was able to detect phenolic compounds in a real sample, and the results were in accordance with standard spectrophotometric assays. Therefore, the innovatively-designed biosensor hereby proposed is a promising tool for phenolic compound detection and quantification when environmental contaminants are concerned.

The Use of a Polyphenoloxidase Biosensor Obtained from the Fruit of Jurubeba (Solanum paniculatum L.) in the Determination of Paracetamol and Other Phenolic Drugs.

The vegetable kingdom is a wide source of a diverse variety of enzymes with broad biotechnological applications. Among the main classes of plant enzymes, the polyphenol oxidases, which convert phenolic compounds to the related quinones, have been successfully used for biosensor development. The oxidation products from such enzymes can be electrochemically reduced, and the sensing is easily achieved by amperometric transducers. In this work, the polyphenoloxidases were extracted from jurubeba (Solanum paniculatum L.) fruits, and the extract was used to construct a carbon paste-based biosensor for pharmaceutical analysis and applications. The assay optimization was performed using a 0.1 mM catechol probe, taking into account the amount of enzymatic extract (50 or 200 µL) and the optimum pH (3.0 to 9.0) as well as some electrochemical differential pulse voltammetric (DPV) parameters (e.g., pulse amplitude, pulse range, pulse width, scan rate). Under optimized conditions, the biosensor was evaluated for the quantitative determination of acetaminophen, acetylsalicylic acid, methyldopa, and ascorbic acid. The best performance was obtained for acetaminophen, which responded linearly in the range between 5 and 245 µM (R = 0.9994), presenting a limit of detection of 3 µM and suitable repeatability ranging between 1.52% and 1.74% relative standard deviation (RSD).

Protective Effects of Ellagic Acid on Cardiovascular Injuries Caused by Hypertension in Rats.

Ellagic acid is described as having antioxidant and antiproliferative properties. Hence, it was hypothesized that ellagic acid could improve cardiovascular damage caused by hypertension. In this work, hypertension was induced in rats with Nω-Nitro-L-arginine methyl ester hydrochloride (60 mg/kg/day in drinking water) for 6 weeks. Ellagic acid was coadministered (10 or 30 mg/kg/day by gavage) between the second and sixth week. Blood pressure was recorded every week by tail-cuff plethysmography. After 6 weeks, the rats were sacrificed, the hearts and kidneys were weighed, and blood was collected. Aortas were isolated and set up to isometric recordings in an organ bath for histological assay and measuring of calcium content. Hypertension (233.6 ± 9.5 mmHg) was reduced (p < 0.01) by treatment with ellagic acid 10 or 30 mg/kg. The blood levels of nitrate/nitrite were reduced in hypertensive rats and the ellagic acid restored these levels. While the vascular relaxations to acetylcholine and sodium nitoprusside and the contraction to phenylephrine were impaired in the hypertensive group, they were improved after ellagic acid treatment. The alkaline phosphatase activity was increased by hypertension and returned to control levels after ellagic acid treatment. In the aorta, the administration of ellagic acid resulted in less aortic wall thickening and less calcification. In conclusion, ellagic acid attenuates hypertension, possibly improving nitric oxide bioavailability. The vascular response to acetylcholine, sodium nitroprusside, and phenylephrine was impaired by hypertension and improved after treatment with ellagic acid. Moreover, plasmatic alkaline phosphatase activity, calcium content, and hypertrophy in vascular tissues during hypertension were attenuated by treatment with ellagic acid.

Pharmacotherapy of adolescents in the use of psychoactive substances

The use of Psychoactive Substances brings problems in several areas of the subject's life such as: health, psychological and social. It´s necessary evaluate the factors involved in drug use and potential drug interactions (PDI) in adolescents using psychoactive substances. It was a Cross-sectional, analytical and quantitative study. The research was carried out at the Center for Psychosocial Care and other drugs for children and adolescents 24h, with adolescents under 18 years of age, using medication. The data were obtained by reviewing the charts and the potential interactions were evaluated through the database Micromedex® and Medscape®. Of the 159 records used, there were 815 PDI. By gravity were 59.4% moderate, 23.8% secondary, 15.7% severe and 1.1% contraindicated. The drugs that presented the most PDI were Chlorpromazine (32.3%) and Diazepam (19.6%). The factors involved in polypharmacy were total PDI and those involved in the occurrence of total PDI were studying and the quantity diagnostic hypotheses. Due to the high PDI index, the relationship with polypharmacy and a high number of diagnostic hypotheses, it is necessary to increase the attention of health professionals regarding the topic and the development of protocols to support decision making.(AU)

Solanum melongena polyphenol oxidase biosensor for the electrochemical analysis of paracetamol.

A new strategy for the construction of a polyphenol oxidase carbon paste biosensor for paracetamol detection is reported. The eggplant (Solanum melongena) was processed to collect the polyphenol oxidase as an enzyme that was incorporated in the carbon paste sensor construction. The constructed sensor displayed high sensitivity and good selection for paracetamol detection and recognition. Optimized conditions included pH 6.0 (highest activity), pH 7.0 (highest stability), pulse amplitude of 50 mV, and 15% of vegetable extract per carbon paste. The sensor displayed a linear range from 20 to 200 µM, with a detection limit of 5 µM. Application of the sensor to paracetamol determination in tablet and oral solutions have shown satisfactory results. The efficiency of the method showed very good repeatability ranging between 1.26 and 1.72% relative standard deviation for interday analysis, while recoveries for paracetamol varied between 97.5 and 99.8% for the voltammetric determination. The strategy for a simple, low cost, and efficient eggplant polyphenol oxidase sensor showcased in this work provides an opportunity for the detection of other phenolic compounds in various matrices.

Lipase entrapment in PVA/Chitosan biodegradable film for reactor coatings.

This study reports the development and characterization of novel biodegradable film, based on chitosan and polyvinyl alcohol containing lipase entrapped. The films showed a thickness of 70.4 and 79 µm to PVA/Chitosan and PVA/Chitosan/Lipase, respectively. The entrapment of lipase in PVA/Chitosan film resulted in increasing of 69.4% tensile strength (TS), and 52.4% of elongation. SEM images showed the formation of a continuous film, without pores or cracks. The lipase entrapment efficiency was estimated in 92% and the films were repeatedly used for 25 hydrolytic cycles, maintaining 62% of initial activity. The PVA/Chitosan/Lipase film was used for olive oil hydrolysis of high performance. These results indicate that PVA/Chitosan/Lipase is a promising material for biotechnology applications such as triacylglycerol hydrolysis and biodiesel production.