Evaluation of oxidative stress and its association with drug therapy in inpatients treated for cocaine dependence.

The use of cocaine affects several systems and organs of the human body and the consumption of this substance leads to an increase in the production of reactive oxygen species, and to the reduction of antioxidant defenses. The aim of this study was to evaluate the oxidative stress (OS), biochemical and hematological parameters in patients hospitalized for treatment of cocaine addiction, comparing levels at hospital admission and discharge. Forty patients were included in the study. OS was evaluated using catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GPx), total antioxidant power (FRAP), malondialdehyde (MDA), and sulfhydryl group (GS). The medications used during hospitalization were registered and their influence on the parameters of OS was analyzed. After the hospitalization period, there was an increase in GGT levels, a reduction in SOD activity, and an increase in GPx activity and FRAP levels. Carbamazepine users had higher SOD values and lower FRAP values at hospital discharge. The use of chlorpromazine caused differences in creatinine and gamma-glutamyltransferase (GGT) serum leves, and the levels of glutamic oxalacetic transaminase (TGO), MDA, and FRAP were increased at hospital discharge. Haloperidol and thiamine during hospitalization interfered with alkaline phosphatase levels. The use of risperidone caused an increase in the levels of SOD, and folic acid use was associated with lower levels of GPx and higher levels of glutamic-pyruvic transaminase (TGP) and alkaline phosphatase. Drug rehabilitation treatment was effective in decreasing oxidative damage represented by the reduction of biological markers.

Evaluation of hemaPEN® sampling device for measurement of cocaine and metabolites in capillary blood by LC-MS/MS.

Background: Dried blood spot sampling has been reported for on-site collection of specimens, but measurements are affected by blood hematocrit, and special handling is required, especially for forensic applications. The hemaPEN® blood collection device was developed to produce spots with constant volume. Results: Linearity between 1 and 500 ng/ml was shown for cocaine and the metabolites benzoylecgonine and cocaethylene. The assay demonstrated acceptable precision and accuracy, and analytes were stable for 7 days when kept inside hemaPEN devices. Accuracy of the assay was affected by hematocrit but was within acceptable limits. Conclusion: Use of the hemaPEN, which retains dried blood within the device, could be advantageous for the quantification of illicit drugs in capillary blood compared with conventional dried blood spot collection.

Assessment of potential in vitro toxicity of Cissus sicyoides L. and Wedelia paludosa DC. leaves water extracts.

Medicinal plants have been employed as an alternative method to treat diabetes. One is Cissus sicyoides, a plant from the Amazon region (Northern Brazil), which is morphologically similar to Wedelia paludosa, a plant easily found in Southern Brazil. Thus, this study aimed to assess the potential toxicity of C. sicyoides and W. paludosa's leaves water extracts. Through phytochemical screening, phenolic compounds and alkaloids were observed in both species and coumarins only W. paludosa's aqueous extract. Phenolic compounds were quantified in both extracts and C. sicyoides presented 1.36 ± 0.04 mg/pyrogalic acid equivalent (PAE), whereas W. paludosa presented 3.27 ± 0.07 mg/PAE. Total antioxidant power was measured by the ferric reduction assay. Cissus sicyoides exhibited total antioxidant activity of 748.0 ± 104.5 µM and W. paludosa, 1971.5 ± 141.0 µM. Cissus sicyoides showed an inhibition rate for the alpha-glucosidases enzyme assay of 55.2 ± 1.7% and W. paludosa, 85.8 ± 9.7%. The formation of reactive oxygen species was evaluated by the DCFH-DA method, its formation being higher in W. paludosa's water extracts than in C. sicyoides. Cell viability was evaluated by the Sulforhodamine B and MTT assays. Wedelia paludosa's extracts' exposure presented a cell viability close to positive control starting from 2 mg/mL to 30 mg/mL, whereas C. sicyoides demonstrated statistical significant low viability at the highest concentration when compared with the negative control. Moreover, cell death mechanism was investigated, having W. paludosa's extract indicated death by necrosis. The results suggest low toxicity for C. sicyoides' extract and high toxicity for W. paludosa's extract.

Neuropsychological assessment after long-term omeprazole treatment.

Recent studies suggest that Omeprazole, a widely used treatment for gastric acid-related disorders, may have a significant effect on human cognition. However, there is no consensus on the matter. Though some studies suggest the drug is associated with an increased risk of cognitive decline, memory impairment, and dementia, this issue has not been sufficiently studied. Therefore, the goal of this study was to investigate the cognitive impairments associated with long-term Omeprazole treatment, with a focus on memory, attention, and executive functions. Additionally, we sought to verify whether the duration of treatment was associated with the magnitude of the associated cognitive impairments. The sample consisted of 30 participants of both genders treated with Omeprazole (experimental group) and 30 participants who did not use the drug (control group). The cognitive assessment battery: Verbal Fluency, Rey Auditory-Verbal Learning, Attention Assessment Battery, Five Digit Test, Hayling Test, and NEUPSILIN Subtest. The groups were compared using Student's T-tests, and the association between treatment duration and cognitive performance was examined using Pearson's coefficients. The results showed significant group differences in verbal fluency, short-term episodic memory, selective attention, and executive functions. The duration of Omeprazole treatment was also positively associated with the magnitude of cognitive impairment.

Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice.

Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects.

Evaluation of oxidative stress biomarkers and liver and renal functional parameters in patients during treatment a mental health unit to treat alcohol dependence.

Alcohol dependence is one of the main reasons for inpatient admission to psychiatric hospitals. The abuse of this chemical substance can cause modifications in our organism and among them, variations in the oxidative stress parameters. Therefore, the aim of this study is to evaluate patients admitted to a psychiatric hospital unit to treat alcohol dependence, comparing oxidative stress, renal and hepatic function parameters from the moment of admission to those obtained at discharge. Hepatic function was verified through gamma-glutamyl-transferase (GGT), alkaline-phosphatase (ALP), aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) activity measurements. Urea and creatinine serum levels were measured for kidney function evaluation. Oxidative stress was evaluated by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), ferric reducing antioxidant power (FRAP) and malondialdehyde (MDA). Medications used during hospital stay were record and their influence over the measured parameters analyzed. Twenty-eight patients (82% male, 44 ± 13 years old) were included in this study. A significant increase in BMI of patients after the period of hospitalization could be observed. There were reductions in creatinine, AST, ALT, GGT and ALP serum levels. SOD levels were lower at discharge, while GPx and FRAP presented higher levels. Chlorpromazine use showed influence over some hepatic function markers (ALT, GGT and ALP) and oxidative stress parameters (CAT and GPx); while carbamazepine use influenced GGT and FRAP. Patients on alcohol dependence treatment had significant improvements of renal and hepatic function parameters and higher GPx and FRAP values after the hospitalization period, which indicates reversion of alcohol effects over oxidative stress parameters.

Cognition, oxidative stress and vitamin B12 levels evaluation on patients under long-term omeprazole use.

OBJECTIVES: To evaluate the differences concerning cognitive performance, oxidative stress and vitamin B12 levels in omeprazole users under treatment for longer than six months. METHODS: A case-control study was developed with 44 omeprazole users (OU; 81.8 % female, 66 ± 8.7 years old) and 35 nonusers (NOU; 88.6 % female, 62 ± 8.7 years old). The cognitive ability was assessed through tests approaching attention, memory and executive functions. The vitamin B12 was dosage using a chemiluminescent immunoassay and oxidative stress analysis, based on the evaluation of malondialdehyde, enzymatic activity of extracellular superoxide dismutase, glutathione peroxidase, catalase and the ferric reducing antioxidant power in plasma. KEY FINDINGS: A significant increase of the ferric reducing antioxidant power [omeprazole users (OU) group = 1690 µM ± 441 and nonusers (NOU) group = 1308 ± 616; P value=0.002] and a decrease on glutathione peroxidase levels [OU group = 0.534 (0.27-10.63) and NOU group = 71.86 (14.36-173.1); P value=0.006] were found on omeprazole users group, as well as differences on cognitive performance, with impairments on executive functions, automatic and attentional processing. CONCLUSIONS: Long-term use of omeprazole is suggested to induce an oxidative stress condition, which causes neurotoxicity and cognitive decline.

Analysis of Adherence to Fluoxetine Treatment through its Plasma Concentration

Abstract Depression plays an important role in non-adherence to medical recommendations. Fluoxetine is a first line of depression treatment. This study aimed to evaluate adherence to drug therapy in fluoxetine users by different methods. A cross-section study was conducted with 53 depressed patients on fluoxetine for at least six months. Drug therapy adherence was assessed by validated questionnaires [Brief Medication Questionnaire (BMQ) and Morisky-Green test (MG)] and by the blood concentration of fluoxetine and its active metabolite norfluoxetine. Blood samples were taken before the daily first dose of fluoxetine. The plasmatic concentration of fluoxetine and norfluoxetine indicated that 58.5% volunteers were within the recommended therapeutic range and thus considered adherent to drug therapy. However, questionnaires indicated a non-adherent majority: 41.5% patients had a high degree of adherence in MG and only 13.2% were adherent to pharmacological treatment in BMQ. Most fluoxetine users showed a plasma concentration of fluoxetine and norfluoxetine within the therapeutic range, despite the low adherence to the drug therapy evaluated by the questionnaires. Thus, we suggest that plasma levels of fluoxetine and norfluoxetine could be used as the main method to check adherence to treatment.

Determination of cortisol in hair using UHPLC-MS/MS: application to patients admitted for ethanol dependence treatment.

Aim: Cortisol hair levels can be used to evaluate chronic stress status. In this context, an improved UHPLC-MS/MS assay for the determination of cortisol in hair was developed and validated. Materials & methods: Hair was extracted with methanol for 4 h at 25°C. Chromatographic run time was 5.5 min. The assay was linear in the range of 1-250 pg mg-1. Precision was 3.6-12.2% and accuracy 97.1-103.8%. The method was applied in hair from 19 volunteers admitted at a rehabilitation clinic, with ethanol consumption classified using ethyl glucuronide hair levels. Conclusion: Abstinent/chronic moderate ethanol consumers had significantly lower cortisol hair levels than chronic excessive consumers. This is the first study evaluating cortisol hair levels in ethanol abuse patients using an objective marker for ethanol consumption.

Effect of pesticide exposure on total antioxidant capacity and biochemical parameters in Brazilian soybean farmers.

Farmers represent a population highly vulnerable to the toxic effects of pesticide exposure. Antioxidant capacity and biochemical parameters have been used as biomarkers of occupational exposure to pesticides. The aim of this study was to evaluate hepatic and renal parameters as well as butyrylcholinesterase (BChE) activity and ferric-reducing ability of plasma (FRAP) considering high and low exposure periods in soybean farmers in southern Brazil. The exposed group consisted of 50 soybean farmers. Two control groups were used, composed by 35 (Novo Hamburgo control group) and 28 (Sertão control group) subjects not exposed to pesticides. Farmers blood samples were collected during the high and low pesticide exposure periods. BChE, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), urea, and creatinine levels were determined. The FRAP assay was carried out to evaluate the antioxidant potential in the exposed group. Considering the exposed group, significantly lower BChE and increased AST activity were observed during high pesticide exposure period as well as higher FRAP, urea and creatinine levels; however, ALT and GGT did not differ between the two periods. When compared with the control groups, only urea and creatinine were higher in the exposed group. The present results indicate that occupational exposure to mixtures of pesticides might elicit adverse effects at the biochemical level. In addition, the study highlights the importance in considering periods of a same crop season with different degree of pesticide exposure during biologic monitoring of these biochemical parameters.

In vitro cytotoxic and genotoxic effects of Cissus verticillata and Sphagneticola trilobata used for treatment of Diabetes Mellitus in Brazilian folk medicine

Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.

Simultaneous Determination of Cocaine and Metabolites in Human Plasma Using Solid Phase Micro-Extraction Fiber Tips C18 and UPLC-MS/MS.

The determination of cocaine (COC) and its metabolites ecgonine methyl ester (EME), benzoylecgonine (BZE), norcocaine (NCOC) and cocaethylene (CE) in human plasma is relevant in clinical and forensic toxicology. An efficient extraction and clean-up of plasma specimens for the simultaneous determination of BZE along with COC and basic metabolites is challenging due to their widely different polarities and ionization characteristics. Recently, biocompatible SPME LC tips C18 became commercially available. We applied SPME LC tips C18 to the simultaneous extraction of COC, BZE, EME, NCOC, and CE by direct immersion of the fiber in plasma diluted with a buffer at pH 8.0. Analytes were desorbed from the fiber to methanol containing formic acid and injected into a UPLC-MS/MS system. The assay was linear from 5 to 500 ng mL-1. Precision assays presented CV% in the range of 2.22 to 10.54%, and accuracy was in the range of 93.4-108.1%. The assay requires minimal quantities of plasma and organic solvents, allowing multiple extractions in parallel. Biocompatible SPME is a promising alternative for preparing biological samples prior to drug measurement by UPLC-MS/MS.

Simultaneous determination of cocaine, ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine in dried blood spots by ultra-performance liquid chromatography coupled to tandem mass spectrometry.

Cocaine (COC) is one of the most widely abused drugs in the world and its sensitive and its reliable measurement in blood is of great importance in the field of forensic and clinical toxicology. Additionally, the determination of COC metabolites such as benzoylecgonine (BZE), cocaethylene (CE), ecgonine methyl ester (EME), and norcocaine (NCOC) are also of complementary diagnostic value. The quantification of COC and metabolites in dried blood spots (DBS) may be an alternative to conventional collection methods with several advantages, including easier, on-site, collection, transportation and storage. In this study, we present a simple and comprehensively validated UPLC-MS/MS assay to measured COC, BZE, EME, NCOC and CE in DBS. The evaluated assay was linear from 5-500 ng mL-1. Precision assays presented CV% of 1.27-6.82, and accuracy in the range of 97-113.78%. Low haematocrit values had a negative impact in the assay accuracy. COC, BE, NCOC and CE measurements can be made reliably in DBS stored for 14 days at room temperature, as well as at -20 °C and 45 °C. All evaluated compounds can be measured in DBS maintained at -20 °C for 14 days. DBS sampling can be used for the clinical evaluation of the exposure to COC, being an alternative for collection, short-term storage and transportation of blood at room and high temperatures.

Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity.

BACKGROUND: Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established based on patient's body surface area, an approach associated with large inter-individual variability in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1. Genetic polymorphisms in the UGT1A1 gene are associated to higher exposures to SN-38 and severe toxicity. Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available, with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization. The aim of this manuscript is to review the available evidence supporting pharmacogenetic and pharmacokinetic dose individualization of IRI in order to reduce the occurrence of severe toxicity during cancer treatment. METHODS: The PubMed database was searched, considering papers published in the period from 1995-2017, using the keywords irinotecan, pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, pharmacokinetics and pharmacodynamics, either alone or in combination, with original papers being selected based on the presence of relevant data. CONCLUSION: The findings of this review confirm the importance of considering individual patient characteristics to select IRI doses. Currently, the most straightforward approach for IRI dose individualization is UGT1A1 genotyping. However, this strategy is sub-optimal due to several other genetic and environmental contributions to the variable pharmacokinetics of IRI and its active metabolite. The use of dried blood spot sampling could allow the clinical application of limited sampling and population pharmacokinetic models for IRI doses individualization.

Simultaneous determination of fluoxetine and norfluoxetine in dried blood spots using high-performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: Therapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability. OBJECTIVES: The aim of this study was to develop and validate an LC-MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS. DESIGN AND METHODS: The assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore® C18 column (100×2.1mm, 2.6µm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy. RESULTS: The assay was linear in the range 10-750ngmL-1. Precision assays presented CV% of 3.13-9.61 and 3.54-7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98-110.44% and 100.25-105.8%. FLU and NFLU were stable at 25 and 45°C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of -0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL-1. CONCLUSIONS: The presented data support the clinical use of DBS for therapeutic drug monitoring of FLU.

Oxidative stress in patients with type 2 diabetes mellitus treated with metformin / Estresse oxidativo em pacientes com diabetes mellitus tipo 2 em tratamento com metformina

AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up. METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients' questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson's correlation and Spearman's correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and end of the study was evaluated using Student's t-test or Wilcoxon U test. The significance level was set at 5%. RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2 , who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient. CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

OBJETIVOS: Avaliar parâmetros de estresse oxidativo em pacientes com diabetes mellitus tipo 2 em uso de metformina, relacionando estes valores a seus efeitos adversos, níveis plasmáticos, controle glicêmico, complicações diabéticas, perfil lipídico, e a influência do acompanhamento farmacoterapêutico. MÉTODOS: Foram avaliados pacientes com diabetes mellitus tipo 2, em uso de metformina, em acompanhamento farmacoterapêutico por quatro meses. O acompanhamento farmacoterapêutico consistiu na prestação de informações e no esclarecimento de dúvidas dos pacientes sobre a medicação e a doença. Além disto, foram verificados os horários, as doses e a presença ou não de efeitos adversos relacionados ao uso de metformina. Foram avaliados perfil glicêmico e lipídico, estresse oxidativo (superóxido dismutase e malondialdeído) e metformina plasmática. Foram realizados os testes de correlação de Pearson e de Spearman para avaliar as relações entre as variáveis no início do estudo. Para testar a diferença entre os grupos com e sem complicações diabéticas, foram utilizados o t-teste independente ou o teste U de MannWhitney. A gama de valores entre o início e o final do estudo foi avaliada utilizando o teste t de Student ou o teste de Wilcoxon U. Foi adotado um nível de significância de 5%. RESULTADOS: A amostra inicial foi composta por 49 pacientes com idade de 59±9 anos e índice de massa corporal de 29,8±5,1 kg/m2 , com diabetes por uma mediana de tempo de 36 (intervalo interquartil 1-240) meses e em uso de metformina há uma mediana de 36 (intervalo interquartil 1-180) meses. Vinte e cinco pacientes deixaram o estudo entre a segunda e a quarta reunião. Os níveis de malondialdeído diferiram entre antes e após o acompanhamento farmacoterapêutico, correlacionando-se positivamente com glicemia, glicohemoglobina e triglicerídeos e negativamente com metformina e superóxido dismutase. Encontrou-se elevação da glicemia, glicohemoglobina e malondialdeído, e diminuição da metformina no grupo com complicações diabéticas, e foi identificada correlação entre malondialdeído e o número de complicações diabéticas por paciente. CONCLUSÕES: Nesta amostra de pacientes com diabetes mellitus tipo 2 em tratamento com metformina, o estresse oxidativo foi mais pronunciado nos que apresentavam pior controle glicêmico e complicações diabéticas.

The influence on DNA damage of glycaemic parameters, oral antidiabetic drugs and polymorphisms of genes involved in the DNA repair system.

The hyperglycaemia seen in type 2 diabetes mellitus (DM2) is associated with increased oxidative stress and production of reactive oxygen species, both of which are factors that can provoke DNA damage. Notwithstanding, other factors, including medications and individual susceptibility, can also induce this type of DNA lesion. The objective of this study was, therefore, to investigate the influence of glycaemic control, oral antidiabetic drugs (metformin and glibenclamide) and polymorphisms of the XRCC1 and XRCC3 genes on the frequency of DNA damage in DM2 patients, which was accessed by the cytokinesis-block micronucleus cytome and the comet assays on the ex vivo mitogenically stimulated lymphocytes. The 53 people recruited to take part in the study were already on treatment with metformin and were followed for 5 months. Ten of these patients were put on combined treatment with the addition of glibenclamide. It was observed that the greater the plasma metformin concentration, the lower the frequency of micronuclei (MN) in the sample total (P = 0.009) and also that the subset of patients using combined treatment including glibenclamide had a significantly higher MN rate 90 days after starting combined treatment (P = 0.024). In the subset who only took metformin, the rate of MN was significantly higher among carriers of the 399Gln allele on the XRCC1 gene (P = 0.008). In addition, homozygotes for the 241Thr allele exhibited a significant increase in MN in the combined treatment group (P = 0.008). Our results suggest that different combinations of oral antidiabetic drugs and polymorphisms on genes involved in the DNA damage repair system could influence the frequency of this type of chromosome lesion, which can be a useful biomarker for assessing the risk of developing cancer.

Avaliação do uso de medicamentos em uma unidade pediátrica de um hospital privado do sul do Brasil / Assessment of medication used in a private hospital pediatric unit in south Brazil

A avaliação do uso racional de medicamentos em pediatria é importante, já que este grupo de pacientes traz desafios diários relacionados à administração, posologia e preparação dos medicamentos. Neste estudo, foram analisados 382 prontuários de pacientes de uma unidade pediátrica hospitalar, sendo avaliados o número de medicamentos prescritos, a via de administração, a adequação da dose prescrita e o modo de diluição. A divisão entre sexos foi similar, com uma média de quatro medicamentos prescritos por paciente. A via intravenosa foi a mais utilizada. As classes farmacológicas mais prescritas foram analgésicos e antibacterianos. As principais inadequações de doses foram verificadas com gentamicina, penicilina, carbamazepina e paracetamol. Verificou-se que o procedimento de diluição é realizado com volume fixo e um único tipo de diluente para todos os fármacos, sendo que o volume dos pós não é considerado no ajuste do volume final de reconstituição. Desta forma, percebe-se que a maioria das falhas encontradas poderia ser minimizada mediante a atuação de farmacêuticos disponibilizando informações sobre medicamentos à equipe de saúde.

It is very important to assess the rational use of medicines in pediatrics since this group of patients raises daily challenges in the administration, dosage and preparation of prescribed medication. In this study, the medical records of 382 patients in a Pediatric Unit of a private hospital were analyzed. We assessed the number of medicines prescribed, administration route, dose prescribed and dilution procedure. The numbers of female and male children were similar. An average of 4 medicines was prescribed for each patient. The intravenous route of administration was the most frequently used. The worst errors in the prescribed dose were found for gentamycin, penicillin, carbamazepine and acetaminophen. It was discovered that all hospital dilution procedures were done with a fixed volume of the same diluent for all prescribed drugs and the powder volume was ignored when the final volume of the reconstituted solutions was adjusted. Thus, it is clear that most of the faults found could be minimized by the action of pharmacists providing drug information to the health care team.

Acompanhamento farmacoterapêutico em pacientes dislipidêmicos de um lar de idosos da cidade de Novo Hamburgo-RS / The pharmacotherapeutic follow-up in dyslipidemic patients of a nursing home in Novo Hamburgo city, state of Rio Grande do Sul, Brazil

INTRODUÇÃO: A partir do último século, observou-se aumento na expectativa de vida e na incidência de patologia na população idosa, principalmente doenças crônicas. OBJETIVO: Avaliar o efeito do acompanhamento farmacoterapêutico (AF) em pacientes dislipidêmicos de um lar de idosos da cidade de Novo Hamburgo, RS. METODOLOGIA: Trata-se de estudo quantitativo, observacional com delineamento longitudinal retrospectivo, que avaliou 50 pacientes idosos residentes de um lar geriátrico (80,2 ± 7,64 anos, 32 mulheres). Foi avaliado o perfil lipídico desses pacientes (colesterol total, triglicerídeos, HDL e LDL) antes e após AF de um ano. A análise dos resultados ocorreu por meio de estatística descritiva e teste t Student ou U de Mann Whitney para amostras pareadas. RESULTADOS: 56% dos pacientes apresentaram alteração no perfil lipídico no início do estudo e, 30% ao final, ocorrendo significativa melhora após o AF. Além disso, os níveis de colesterol total apresentaram diminuição favorável após um ano de acompanhamento (206 ± 53 vs. 180 ± 43 mg/dL; P = 0,009). A maioria dos pacientes que apresentou diagnóstico de dislipidemia utilizava medicamentos há pelo menos três meses para o tratamento dessa patologia (estatinas e fibratos). A maioria desses pacientes utilizava os medicamentos de forma correta. CONCLUSÃO: Conclui-se que os pacientes tiveram melhora no seu perfil lipídico após um ano de acompanhamento.

INTRODUCTION: Since the last century, life expectancy and the incidence of disease in the elderly have increased, especially chronic diseases. OBJECTIVE: This study aims to evaluate the pharmacotherapeutic follow-up(PF) in dyslipidemic patients of a nursing home in Novo Hamburgo city, state of Rio Grande do Sul, Brazil. METHODOLOGY: This is a quantitative, observational study with a longitudinal retrospective design, evaluating 50 elderly patients who live in a nursing home (80.2 ± 7.64 years old, 32 women). We assessed the lipid profile of these patients (total cholesterol, triglycerides, HDL and LDL) before and after one-year PF. The analysis was conducted through descriptive statistics and Student t test or U of Mann Whitney test for paired samples. RESULTS: 56% of the patients presented changes in lipid profile in the beginning of the study and 30% one year later, with significant improvement of the lipid profile after the monitoring. Moreover, total cholesterol levels showed a favorable decrease after a year of monitoring (206 ± 53 vs. 180 ± 43 mg/dL; P = 0.009). Most patients diagnosed with dyslipidemia were using drugs, for at least three months, to treat this pathology (statins and fibrates). The majority of these patients used them correctly. CONCLUSIONS: The patients had significant improvement in their lipid profile after one year of monitoring.

Possíveis interações medicamentosas entre os anti-hipertensivos e antidiabéticos em participantes do Grupo HIPERDIA de Parobé, RS(Uma análise teórica) / Potential interactions between anti-hypertensive and anti-diabetic drugs in members of the Group Hiperdia in Parobé, RS, Brazil (A Theoretical Analysis)

Devido à alta incidência simultânea de hipertensão arterial sistêmica e diabetes mellitus, é comum encontrar pacientes que usam anti-hipertensivos e antidiabéticos simultaneamente. Desta forma, torna-se importante identificar as possíveis interações medicamentosas no tratamento da hipertensão arterial e do diabetes e realizar manejo farmacoterapêutico adequado para evitar efeitos adversos graves ou até a morte. Este trabalho teve como objetivo identificar possíveis interações com os medicamentos anti-hipertensivos e antidiabéticos em participantes idosos do grupo HIPERDIA no município de Parobé/RS. Trata-se de um estudo quantitativo, observacional e transversal e foi realizado através de um questionário estruturado aplicado em 45 (39 idosos, 37 com interações medicamentosas) participantes do programa HIPERDIA. Foram identificadas 144 possíveis interações medicamentosas, sendo 30% desejáveis e 70% indesejáveis. Destas indesejáveis, 85% classificadas como moderada com maior ocorrência da associação de captopril e ácido acetilsalicílico, 5% grave (interação de diurético de alça com digitálico) e 10% leves. Das desejáveis, a associação de captopril e hidroclorotiazida teve maior ocorrência. Este estudo revelou um alto índice de possíveis interações medicamentosas em idosos participantes do programa HIPERDIA. A maioria das interações pode comprometer a segurança do paciente, evidenciando a relevância deste tema e a necessidade de avaliar e monitorar a terapêutica medicamentosa no idoso, no sentido de prevenir e diminuir as consequências dos efeitos decorrentes de potenciais interações medicamentosas.

Owing to the high incidence of concurrent hypertension and diabetes mellitus, it is common to find patients using antihypertensive and anti-diabetic drugs simultaneously. Thus, it is important to identify drug interactions in the treatment of hypertension and diabetes and to carry out pharmacotherapy monitoring to avoid serious adverse effects or even death. The aim in this was to identify potential interactions between antihypertensive and hypoglycemic agents in elderly participants of the group Hiperdia in the town of Parobé (RS). This is a cross-sectional, quantitative and observational study and was conducted by means of a structured questionnaire applied to 45 (39 elderly, 37 with drug interactions) members of the group. We identified 144 potential drug interactions, 30% of which were desirable and 70% undesirable. Among the latter, 85% were classified as moderate, the most frequent association being that of captopril and acetylsalicylic acid, 5% as severe (interaction of loop diuretics with digitalis) and 10% as light. Among the desirable interactions, the combination of captopril and hydrochlorothiazide occurred most frequently. This study revealed a high rate of potential drug interactions in elderly members of Hiperdia. Most interactions can jeopardize patient safety, highlighting the importance of this matter and the need to assess and monitor drug therapy in the elderly, in order to prevent and mitigate the consequences of potential drug interactions