Eficacia y tolerabilidad Resultados del tratamiento para la fibrosis pulmonar idiopática. Experiencia de la vida real / Efficacy and Tolerability Outcomes of Treatment for Idiopathic Pulmonary Fibrosis. Real-life Experience

Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad progresiva y cró-nica con muy mal pronóstico. Actualmente, existen dos fármacos para esta patología. El propósito de nuestro estudio es evaluar los efectos del tratamiento en los pacientes de una consulta en vida real.

Introduction: idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with a very poor prognosis. Two drugs are currently available for this disease. The purpo-se of our study is to evaluate the effects of treatment in patients in a real-life practice.

Drug Profile and Therapeutic Adherence of African-Brazilians with Apparent Resistant Hypertension

Abstract Background Resistant hypertension (RH) is manifested by the presence of blood pressure values resistant to antihypertensive therapy. RH is highly prevalent among black individuals, increasing cardiovascular risk in this population and requiring effective control of this comorbidity. Objectives To investigate the medication profile and therapeutic adherence in black people with apparent RH. Methods This is a cross-sectional study, with a convenience sample of individuals with apparent RH. Data were obtained from medical records. Therapeutic adherence was assessed using the Morisky Therapeutic Adherence Scale of 8 items (MMAS-8) and statistical analysis was performed using the SPSS, version 23. Significance was set at p <0.05. Results Of the 120 individuals, 90 (75%) were women and 72 (60%) were black. Mean SBP was 153.09 (SD 25.59) mm Hg and mean DBP, 90.82 (SD 16.91) mm Hg, with a statistical difference in relation to the target pressure for SBP. Regarding the medication profile, 79.2% of the individuals used the recommended regimen for RH (ACEI / ARB + Diuretic + CCB), with the fourth most used drug being beta-blockers. The average score in MMAS-8 was 6.62 (SD 1.38) points, with 19.2%, 50.0%, and 30.8% showing low, medium, and high adherence, respectively. Conclusions It was evidenced that two-thirds of the individuals did not have high therapeutic adherence and not all used the ideal regimen for the management of RH, nor full doses. Thus, most individuals were probably affected by pseudoresistance, which was initially diagnosed as apparent RH. (Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0)

Pérdida de respuesta a terapia anti-TNF en enfermedad inflamatoria intestinal: experiencia en un hospital de referencia en Lima - Perú / Loss of response to anti-TNF therapy in inflammatory bowel disease: experience in a reference hospital in Lima - Peru

RESUMEN Objetivo: Evaluar la respuesta al tratamiento con anti-TNFs en pacientes con enfermedad inflamatoria intestinal. Materiales y métodos: Estudio prospectivo observacional realizado en el Servicio de Gastroenterología del Hospital Nacional Guillermo Almenara, de enero 2015 a agosto 2018. Resultados: Se evaluó 31 pacientes con enfermedad inflamatoria intestinal que recibían terapia de mantenimiento con Infliximab. Doce (38,7%) pacientes (3 con colitis ulcerativa y 9 con enfermedad de Crohn) presentaron pérdida de respuesta a partir de los 6 meses del inicio de la fase de mantenimiento: 2 entre 6-12 meses, 4 entre 12-18 meses y 6 entre 18-24 meses. Como primera medida se duplicó la dosis (10 mg/kg) a los 12 pacientes, obteniendo respuesta en 6 (50%) luego de 12 semanas. De los 6 pacientes restantes, 4 cambiaron a Adalimumab, 1 paciente presentó cáncer de colon y 1 paciente presentó anafilaxia y sarcoidosis. De los pacientes que recibieron Adalimumab, 3 presentaron recidiva endoscópica (75%) a partir de los 6 meses y 1 no respondió a la terapia de inducción y fue sometido a colectomía (25%). Conclusiones: Aproximadamente un tercio de nuestros pacientes presentó pérdida de respuesta a terapia de mantenimiento con Infliximab. El escalamiento de dosis como rescate tuvo éxito en la mitad de los pacientes. El cambio a Adalimumab en pacientes con pérdida de respuesta a un primer fármaco anti-TNF no parece ser efectivo.

ABSTRACT Objective: To evaluate the response to treatment with anti-TNFs in patients with inflammatory bowel disease. Materials and methods: Prospective observational study conducted in the Gastroenterology service of the Guillermo Almenara National Hospital, from January 2015 to August 2018. Results: 31 patients with inflammatory bowel disease who received maintenance therapy with Infliximab were evaluated. Twelve (38.7%) patients (3 with ulcerative colitis and 9 with Crohn's disease) presented loss of response after 6 months of the beginning of the maintenance phase: 2 between 6-12 months, 4 between 12-18 months and 6 between 1824 months. As a first step, the dose was doubled (10 mg/kg) to the 12 patients, obtaining a response in 6 (50%) after 12 weeks. Of the remaining 6 patients, 4 switched to Adalimumab, 1 patient presented colon cancer and 1 patient presented anaphylaxis and sarcoidosis. Of the patients who received Adalimumab, 3 had endoscopic recurrence (75%) after 6 months and 1 did not respond to induction therapy and was subjected to colectomy (25%). Conclusions: Approximately one third of our patients presented loss of response to maintenance therapy with Infliximab. The dose escalation as a rescue therapy was successful in half of the patients. The change to Adalimumab in patients with loss of response to a first anti-TNF drug does not seem to be effective.

Predictive factors for loss of response to anti-tnf in crohns disease / Fatores preditivos da perda de resposta aos anti-tnf na doença de crohn

ABSTRACT Background: Anti-TNF drugs are a fundamental part of the treatment of Crohn's disease (CD), so identifying factors related to loss of response is of great importance in clinical practice. Aim: Identify potential factors related to loss of response to anti-TNF agents in Crohn's disease patients. Methods: This is a prospective study of CD patients attending a specialized outpatient clinic using a specific form, including patients with more than one year of follow-up on anti-TNF (Infliximab, Adalimumab or Certolizumab pegol). The information obtained was tabulated and analyzed to identify possible reasons for the loss of response to anti-TNF agents; results were submitted to statistical analysis by chi-square teste considering significant p<0.05. Results: Sixty-four patients were included, most of them females (56.3%), predominant age group between 26 and 55 years, of whom 25 required optimization, 23 remained in remission with the usual dose and interval, and 16 required switch; most of those who needed switch had hematological problems such as anemia and/or had already undergone surgical treatment for CD. Conclusions: Anemia and prior CD surgery have been linked to loss of anti-TNF response.

RESUMO Racional: Os anti-TNF são parte fundamental no tratamento da doença de Crohn (DC), portanto, identificar os fatores relacionados à perda de resposta tem grande importância na prática clínica. Objetivo: Identificar potenciais fatores relacionados a perda de resposta aos agentes anti-TNF em pacientes com DC. Métodos: Trata-se de um estudo prospectivo de pacientes com DC frequentadores de ambulatório especializado por meio de formulário específico, incluindo-se pacientes com mais de um ano de acompanhamento em uso de anti-TNF (Infliximabe, Adalimumabe ou Certolizumabe pegol). As informações obtidas foram tabuladas e analizadas para identificação de eventuais motivos para a perda de resposta aos agentes; os resultados foram submetidos a tratamento estatístico por meio do teste qui-quadrado considerando-se significante p<0,05. Resultados: Foram incluídos 64 pacientes, sendo a maioria do sexo feminino (56,3%), faixa etária predominante entre 26 e 55 anos, dos quais 25 necessitaram otimização, 23 se mantiveram em remissão com a dose e intervalo habituais, e 16 necessitaram troca de medicamento; a maioria dos que necessitaram troca tinham alterações hematológicas como anemia e/ou já haviam sido submetidos a tratamento cirúrgico pela doença. Conclusões: Anemia e operação prévia por DC foram relacionados a perda de resposta aos anti-TNF.

Opioid-induced immunosuppression and carcinogenesis promotion theories create the newest trend in acute and chronic pain pharmacotherapy

Opioids are the main group of pharmacological agents used during the perioperative period and provide a sedative and analgesic component. The observations of opioid consumption in West Europe indicate that this group of drugs is widely used in chronic noncancer pain therapy. Nearly 20 years ago, the first publications indicating that opioids, as an element of perioperative pharmacotherapy in oncologic patients, increase the risk of tumor recurrence and affect further prognosis were presented. The actual publications suggest that there are multifactorial, complex mechanisms underlying the immunological impact and carcinogenesis promotion of opioids and that the intensity varies depending on the type of opioid. There are also questions about the immunosuppressive effects among patients receiving opioids in the treatment of chronic noncancer pain. The aim of the review article is to present information about the action of opioids on the immune system in carcinogenic settings and to define the clinical usefulness of this pharmacological phenomenon.

High frequency of methotrexate intolerance in longstanding rheumatoid arthritis: using the methotrexate intolerance severity score (MISS)

Abstract Background: Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. Methods: This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. Results: Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). Conclusions: The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.(AU)

Postprandial metabolic effects of fructose and glucose in type 1 diabetes patients: a pilot randomized crossover clinical trial

ABSTRACT Objective To test the influence of oral fructose and glucose dose-response solutions in blood glucose (BG), glucagon, triglycerides, uricaemia, and malondialdehyde in postprandial states in type 1 diabetes mellitus (T1DM) patients. Subjects and methods The study had a simple-blind, randomized, two-way crossover design in which T1DM patients were selected to receive fructose and glucose solutions (75g of sugars dissolved in 200 mL of mineral-water) in two separate study days, with 2-7 weeks washout period. In each day, blood samples were drawn after 8h fasting and at 180 min postprandial to obtain glucose, glucagon, triglycerides, uric acid, lactate, and malondialdehyde levels. Results Sixteen T1DM patients (seven men) were evaluated, with a mean age of 25.19 ± 8.8 years, a mean duration of disease of 14.88 ± 4.73 years, and glycated hemoglobin of 8.13 ± 1.84%. Fructose resulted in lower postprandial BG levels than glucose (4.4 ± 5.5 mmol/L; and 12.9 ± 4.1 mmol/L, respectively; p < 0.01). Uric acid levels increased after fructose (26.1 ± 49.9 µmol/L; p < 0.01) and reduced after glucose (-13.6 ± 9.5 µmol/L; p < 0.01). The malondialdehyde increased after fructose (1.4 ± 1.6 µmol/L; p < 0.01) and did not change after glucose solution (-0.2 ± 1.6 µmol/L; p = 0.40). Other variables did not change. Conclusions Fructose and glucose had similar sweetness, flavor and aftertaste characteristics and did not change triglycerides, lactate or glucagon levels. Although fructose resulted in lower postprandial BG than glucose, it increased uric acid and malondialdehyde levels in T1DM patients. Therefore it should be used with caution. ClinicalTrials.gov registration: NCT01713023.

Eficacia y tolerabilidad de la reducción del volumen de polietilenglicol para la preparación para colonoscopia / Effectiveness and tolerability of low volume bowel cleansing polyethylene glycol solution for colonoscopy

Background: A successful colonoscopy depends, among other factors, on a proper colon cleansing. This variable also affects the acceptance of the patient to carry out the study. Aim: To analyze the efficacy and tolerability of a low volume polyethylene glycol formulation (2 liters), compared to the conventional presentation of 4 liters. Material and Methods: Patients referred for a colonoscopy were randomly divided to receive either two or four liter of polyethylene glycol as bowel cleansing, which was assessed using the Boston score. Raters of the latter were blinded to the volume of polyethylene glycol that the patients used. Results: Seventy-four patients participated in the study. Subjects who received a 4 liters preparation had an average Boston score of 7.78, versus 8.16 for patients who received a volume of 2 liters (p = 0.267). No significant differences in tolerability were observed between both groups. No significant differences in the efficacy and tolerability between a conventional or a reduced volume of polyethylene glycol solution for the preparation of a colonoscopy were observed. These findings may be especially important for subgroups of patients with difficulties for oral administration of fluids.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Efecto de Maytenus krukovii "Chuchuhuasi" en el tratamiento de osteoartrosis leve-moderada. Ensayo clínico aleatorizado doble-ciego, controlado con placebo / Safety and efficacy of Maytenus krukovii "Chuchuhuasi" decoction in mild to moderate osteoarthritis. A 4-week randomized double-blind placebo-controlled clinical trial

Objetivo: Evaluar la seguridad y eficacia de Maytenus krukovii "chuchuhuasi" a diferentes dosis en pacientes con osteoartrosis leve-moderada. Materiales y Métodos: Ensayo clínico aleatorizado, doble ciego. Se incluyeron a 50 pacientes con osteoartrosis leve-moderada (clasificación de Kellgren-Lawrence) por cuatro semanas; distribuidos aleatoriamente en tres grupos: I (40mg/kg/día de M. Krukovii); II (80 mg/kg/día de M. Krukovii) y III (15 g/día de Daucus carota como placebo). Se determinó en sangre: Alaninoaminotransferasa (ALT), fosfatasa alcalina (FA), depuración de creatinina, hematocrito, tiempo de protrombina, velocidad de sedimentación y recuento leucocitario. Se evaluó la función, dolor y recorrido articular mediante el Test de WOMAC antes y después de la intervención. Resultados: En el grupo II se encontró una disminución estadísticamente significativa de los valores de ALT, tiempo de protrombina y velocidad de sedimentación. El tiempo de Protrombina (p=0.012) y la velocidad de sedimentación entre el grupo II y el grupo placebo fueron diferentes (p=0.003). El dolor referido fue estadísticamente distinto entre ambos grupos de estudio en comparación con el placebo (p=0.001; diferencia de medias: 1.3±0.89 en ambos casos). En el caso de la capacidad funcional, sólo se encontró diferencia significativa entre el grupo II y el placebo (p=0.001, diferencia de medias: 2.1±1.0). El recorrido articular de rodilla fue diferente entre el grupo I y el grupo III (p=0.004). Conclusión: El uso de M. krukovii "Chuchuhuasi" a dosis de 40 y 80mg/kg p.c. por día, mostró disminuir el dolor referido y mejorar la capacidad funcional en pacientes con diagnóstico de osteoartrosis leve a moderada.

Isolation, identification and characterization of regional indigenous Saccharomyces cerevisiae strains

Abstract In the present work we isolated and identified various indigenous Saccharomyces cerevisiae strains and screened them for the selected oenological properties. These S. cerevisiae strains were isolated from berries and spontaneously fermented musts. The grape berries (Sauvignon blanc and Pinot noir) were grown under the integrated and organic mode of farming in the South Moravia (Czech Republic) wine region. Modern genotyping techniques such as PCR-fingerprinting and interdelta PCR typing were employed to differentiate among indigenous S. cerevisiae strains. This combination of the methods provides a rapid and relatively simple approach for identification of yeast of S. cerevisiae at strain level. In total, 120 isolates were identified and grouped by molecular approaches and 45 of the representative strains were tested for selected important oenological properties including ethanol, sulfur dioxide and osmotic stress tolerance, intensity of flocculation and desirable enzymatic activities. Their ability to produce and utilize acetic/malic acid was examined as well; in addition, H2S production as an undesirable property was screened. The oenological characteristics of indigenous isolates were compared to a commercially available S. cerevisiae BS6 strain, which is commonly used as the starter culture. Finally, some indigenous strains coming from organically treated grape berries were chosen for their promising oenological properties and these strains will be used as the starter culture, because application of a selected indigenous S. cerevisiae strain can enhance the regional character of the wines.

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India

Abstract Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 86–99% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment.

Dentin Bond Strength of a Fluoride-Releasing Adhesive System Submitted to pH-Cycling

To evaluate the microtensile bond strength (µTBS) of a fluoride-containing adhesive system submitted to a pH-cycling and storage time regimen for primary outcomes. As secondary outcomes the fluoride released amount was evaluated. Twelve dentin surfaces from sound third molar were divided into 2 groups according to adhesive systems: Clearfil SE Protect (PB) and Clearfil SE Bond (SE). Sticks obtained (1.0 mm2) from teeth were randomly divided into 3 subgroups according to storage regimen model: immediate (24h); 5-month deionized water (W); and pH-cycling model (C). All sticks were tested for µTBS in a universal testing machine. Fluoride concentration was obtained from 1-4 days and 30-day in W and 1-4 days in demineralization (DE)/remineralization (RE) solutions from C, using a fluoride-specific electrode. µTBS and fluoride released data were, respectively, submitted to ANOVA in a split plot design and Tukey, and Friedman' tests (a=0.05). There was no significant interaction between adhesive system and storage regimen for µTBS. W showed the lowest µTBS values. There was no significant difference between 24 h and C models for µTBS. There was no significant difference between adhesive systems. Failure mode was predominantly cohesive within composite for the 24 h and W, for the C group it was mixed for SE and cohesive within composite for PB adhesive system. Fluoride concentrations in the DE/RE solutions were less than 0.03125 ppm and not detected in W. In conclusion, the fluoride-containing adhesive system performed similarly to the regular one. Hydrolytic degradation is the main problem with both adhesive systems, regardless of fluoride contents.

O objetivo principal desse estudo foi avaliar a resistência de união à microtração de dois sistemas adesivos (com e sem flúor) após a ciclagem de pH e armazenagem em água deionizada. A quantidade de flúor liberada foi avaliada secundariamente. Doze terceiros molares hígidos foram separados em 2 grupos de acordo com o sistema adesivo: Clearfil SE Protect - com flúor (PB) e Clearfil SE Bond - sem flúor (SE). Os palitos (1 mm2) obtidos do mesmo dente foram aleatoriamente divididos em 3 subgrupos de acordo com o meio de armazenagem: em água deionizada por 24h ou 5 meses e ciclagem de pH. Os palitos foram tracionados em uma máquina de ensaio universal a 0,5 mm/min. A concentração de flúor foi analisada em água deionizada (1-4 dias e 30 dias) e na solução remineralizadora e desmineralizadora (1-4 dias) usando um eletrodo específico. Os dados de resistência de união e liberação de flúor foram, respectivamente, submetidos à Análise de Variância em esquema de parcela subdividida e ao teste de Friedman (a=0,05). Não houve nenhuma interação significativa na resistência de união entre os sistemas adesivos e os meios de armazenagem. Os menores valores de resistência de união à microtração foram encontrados para os palitos armazenados em água deionizada. Não houve nenhuma diferença significativa nos valores de resistência de união após 24h e ciclagem de pH. Nenhuma diferença significativa na resistência de união foi observada entre os 2 sistemas adesivos. O modo de falha foi predominantemente coesivo em compósito para os grupos armazenados em água por 24h ou 5 meses para ambos os sistemas adesivos. No grupo submetido à ciclagem, a falha foi mista para o SE e coesiva em compósito para o PB. A concentração de flúor nas soluções DE/RE foi menor que 0,03125 ppm e não detectada em água deionizada. Concluindo, o sistema adesivo com flúor (PB) apresentou performance similar ao sistema adesivo sem flúor (SE). A degradação hidrolítica foi o principal fator para ambos os sistemas adesivos, independente da adição de flúor.

Ground reaction forces during level ground walking with body weight unloading

Background: Partial body weight support (BWS) systems have been broadly used with treadmills as a strategy for gait training of individuals with gait impairments. Considering that we usually walk on level ground and that BWS is achieved by altering the load on the plantar surface of the foot, it would be important to investigate some ground reaction force (GRF) parameters in healthy individuals walking on level ground with BWS to better implement rehabilitation protocols for individuals with gait impairments. Objective: To describe the effects of body weight unloading on GRF parameters as healthy young adults walked with BWS on level ground. Method: Eighteen healthy young adults (27±4 years old) walked on a walkway, with two force plates embedded in the middle of it, wearing a harness connected to a BWS system, with 0%, 15%, and 30% BWS. Vertical and horizontal peaks and vertical valley of GRF, weight acceptance and push-off rates, and impulse were calculated and compared across the three experimental conditions. Results: Overall, participants walked more slowly with the BWS system on level ground compared to their normal walking speed. As body weight unloading increased, the magnitude of the GRF forces decreased. Conversely, weight acceptance rate was similar among conditions. Conclusions: Different amounts of body weight unloading promote different outputs of GRF parameters, even with the same mean walk speed. The only parameter that was similar among the three experimental conditions was the weight acceptance rate. .

Síndrome DRESS y necrólisis epidérmica tóxica por el uso de lamotrigina: a propósito de dos casos / DRESS syndrome and Toxic Epidermal Necrolysis Due to Lamotrigine: a Report of Two Cases

Las reacciones adversas cutáneas a medicamentos (RACM) son una variedad de las múltiples reacciones adversas a los medicamentos (RAM). El Síndrome DRESS es una de ellas y está caracterizada por rash cutáneo, afectación de vísceras y eosinofilia. La Necrólisis Epidérmica Tóxica (NET) o Síndrome de Lyell es otra afección dentro del grupo de las RACM, parecida al Síndrome de Stevens Johnson (SSJ), del cual se diferencia por la extensión de las lesiones cutáneas en más de 30% de la piel. Estas reacciones adversas pueden ser causadas por una variedad de medicamentos entre ellos los antiepilépticos y la asociación de la Lamotrigina con el Ácido Valproico, por acumulación y alargamiento de la vida media del primero. Se presenta el caso de una niña con el antecedente de haber sido tratada con antiepilépticos, entre ellos el Ácido Valproico y que luego de 15 días de ser introducida la Lamotrigina, presentó rash cutáneo, fiebre, alteración de las enzimas hepáticas y eosinofilia importante, cumpliendo los criterios diagnósticos de Síndrome DRESS. El segundo caso corresponde a un niño que estando en tratamiento con antiepilépticos, entre ellos Ácido Valproico se le agregó Lamotrigina por una Epilepsia de difícil control y 20 días después presentó lesiones de piel con afectación de mucosas que se fueron agravando, requiriendo internación en UTI, el cuadro clínico fue compatible con NET. Ambos pacientes tuvieron una evolución favorable .

Adverse cutaneous drug reactions (ACDR) are one of many types of adverse drug reactions (ADR). DRESS syndrome is one of these, and is characterized by askin rash organ involvement, andeo sinophilia. Toxic epidermal necrolysis (TEN), or Lyell's syndrome, is another disease of the ACDR group, andis similar to Stevens-Johnson syndrome (SJS), from which TEN is differentiated by the extension of cutaneous lesions to more than 30% of the skin. These adverse reactions can becaused by avariey of medications, among them anticonvulsiveand use of lamotrigine with valproic acid, due to a resulting increased accumulation and half-life of the lamotrigine. We present the case of a female child previous lyt reated with anti convulsives,including valproic acid, who at 15 days after introduction of lamotrigine presented skinrash, fever, altered liver enzymes, and significant eosinophilia, thereby meeting the diagnostic criteria for DRESS syndrome. The second caseis that o famale child in treatment withant convulsive sincludig valproicacid, to which lamotrigine wasadded duetoo refractory epilepsy, and who 20 days later presented skin lesions with mucosal involvment which worsened with symptoms compatible with TEN and required ICU hospitalization. Both patients progressed favorably.

Avaliação comparativa de eficácia clínica e tolerabilidade para a combinação de Cassia fistula e Senna alexandrina Miller em pacientes com constipação intestinal funcional crônica / Comparative evaluation of clinical efficacy and tolerability for the combination of Cassia fistula and Senna alexandrina Miller in patients with chronic functional constipation

JUSTIFICATIVA E OBJETIVO: A constipação intestinal é um problema crônico, frequente, que afeta a Qualidade de Vida dos indivíduos. O objetivo deste estudo foi avaliar a eficácia clínica e a tolerabilidade da composição Cassia fistula e Senna alexandrina Miller, na apresentação geleia sem açúcar, em pacientes diagnosticados com constipação intestinal funcional crônica. MÉTODOS: Estudo envolvendo 96 voluntários com diagnóstico de constipação intestinal funcional crônica, conforme Critérios de Roma III, randomizados em grupos ativo e placebo. A avaliação da eficácia primária foi realizada por meio da frequência média de evacuações, consistência média das fezes e melhora global da constipação. Foram realizadas ainda avaliações secundárias, como número de dias seguidos sem evacuação, proporção de evacuações com dor, esforço, sensação de evacuação incompleta ou bloqueio, uso de manobras manuais, sujeitos de pesquisa que aderiram às recomendações de hábitos de vida, uso de fármacos de resgate e melhora da constipação segundo avaliação do sujeito de pesquisa. RESULTADOS: A proporção de sujeitos da pesquisa que apresentou melhora global da constipação foi de 65,1% no grupo ativo e de 22,0% grupo placebo (p<0,0001). Para a maioria das avaliações secundárias de eficácia, o grupo ativo apresentou melhor desempenho quando comparado ao grupo pesquisa. De acordo com a avaliação dos sujeitos de pesquisa sobre a melhora da constipação, o grupo ativo apresentou melhor desempenho do que o grupo pesquisa. Quanto à segurança, os dois grupos apresentaram resultados similares. CONCLUSÃO: A geleia sem açúcar composta de Cassia fistula e Senna alexandrina Miller apresentou um comportamento seguro e eficaz, sendo uma alternativa para tratamento da constipação intestinal funcional crônica.

BACKGROUND AND OBJECTIVE: Intestinal constipation is a chronic and frequent problem that affects Quality of Life. The aim of this study was to evaluate the efficacy and tolerability of the composition Cassia fistula and Senna alexandrina Miller, as sugar free jelly, in patients diagnosed with chronic functional constipation. METHODS: We evaluated 96 volunteers diagnosed with functional constipation according to Rome III criteria. Volunteers were randomized into active and placebo groups. Primary efficacy endpoint was evaluated by mean frequency of bowel movements, consistency of stools and global improvement of constipation. Secondary endpoints were evaluated, such as number of days without bowel movements, proportion of bowel movements with pain, with strain, sensation of incomplete or blocked bowel movement, use of, manual maneuvers to facilitate defecation, subjects who adhered to the diet recommendation, use of rescue medication, and level of constipation improvement, according to subject evaluation. RESULTS: Global improvement of constipationwas observed in 65.1% of subjects enrolled in active group versus 22% in placebo group (p<0.0001). For most secondary efficacy evaluations, the active group performed better when compared to placebo group. According to the evaluation of the subjects on the improvement of constipation, the active group performed better than the placebo group. As for security, the two groups showed similar results. CONCLUSION: Cassia fistula and Senna alexandrina Miller sugar free jelly demonstrated to be safe and effective and it can be used as an alternative for the treatment of functional constipation.

Caracterização do complexo Candida glabrata em isolados de hemocultura e avaliação da sensibilidade a antifúngicos / Characterization of the complex Candida glabrata in blood culture isolates and evaluation of sensitivity to antifungals

Candida glabrata assumiu grande importância na clínica médica, desde que, sua resistência adquirida ao fluconazol foi descrita. Além disso, estudos mostraram a fraca atividade in vitro de outros fármacos azólicos contra isolados dessa espécie. C. glabrata é agente de infecções invasivas e o monitoramento da eficácia de antifúngicos usados na prática médica frente a isolados dessa espécie tem relevância clinica. C. bracarensis e C. nivariensis são espécies relacionadas, fenotipicamente, à C. glabrata para as quais há necessidade de métodos moleculares para sua identificação. Na América Latina, a ocorrência de infecções em corrente sanguínea por C. glabrata e espécies correlatas não é tão alta quanto na América do Norte e, por isso, pouco é conhecido sobre sua distribuição e perfil de suscetibilidade a antifúngicos nessa região. Neste estudo, foram analisados 75 isolados com características morfológicas e bioquímicas de C. glabrata, obtidos da corrente sanguínea de pacientes atendidos em hospitais do estado de São Paulo, entre 2007 e 2013. As concentrações inibitórias mínimas (CIM) de cinco fármacos antifúngicos: anfotericina B, caspofungina, voriconazol, fluconazol e itraconazol, foram determinadas pela metodologia de microdiluição de referencia M27-A3 do Clinical and Laboratory Standards Institute (CLSI). A ação fungicida de anfotericina B foi avaliada por método de curva de morte. A pesquisa das duas espécies correlatas foi realizada com metodologia de reação em cadeia da polimerase (PCR) em todos os isolados. Nenhum isolado de C. bracarensis e C. nivariensis foi encontrado neste estudo. Resistência a itraconazol foi encontrada em 18,6 % (14) das cepas de C. glabrata. Altos valores de CIM de voriconazol (> 0,5 mg/L), de acordo com cutoff (ponto de corte) epidemiológico, foram observados para duas cepas...

Candida glabrata has assumed great importance in clinical medicine, since acquired resistance to fluconazole had been described. Furthermore, studies have shown the weak in vitro activity of other azole drugs against isolates of this species. Since C. glabrata is an agent of invasive infections, monitoring the effectiveness of antifungal agents used in medical practice against isolates of this species has become of great importance. C. bracarensis and C. nivariensis are phenotypically related species to C. glabrata and so it is necessary molecular methods to identify properly these members. In Latin America, the occurrence of bloodstream infections in C. glabrata and related species is not as high as in North America, and little is known about their distribution and antifungal susceptibility profile in this region. In this study, we analyzed 75 isolates with morphological and biochemical features of C. glabrata obtained from the bloodstream of patients treated in hospitals in the state of São Paulo, between 2007-2013. The minimum inhibitory concentrations (MIC) of five antifungal drugs, namely: amphotericin B, caspofungin, voriconazole, fluconazole and itraconazole were determined by microdilution reference method M27-A3 from the Clinical and Laboratory Standards Institute (CLSI). The fungicidal action of amphotericin B was evaluated by the method of time-kill curves. The investigation of the two related species was performed with polymerase chain reaction (PCR) in all isolates. No isolate of C. bracarensis and C. nivariensis was found in this study. Resistance to itraconazole was found in 18.6% (14) strains of C. glabrata. High MIC values of voriconazole (> 0.5 mg/L), according to epidemiological cut-off were observed for two strains. The fluconzole-MICs ranged from 4mg/L to 16mg/L, caspofungin-MIC were between 0.03 mg/L and 0.5 mg/L, and amphotericin B-MIC were between 0.12 mg/L and 1 mg/L...

Arsenic tolerance of cyanobacterial strains with potential use in biotechnology / Tolerancia a arsénico de cianobacterias con usos biotecnológicos

The arsenic content of various water bodies in Argentina is higher than the acceptable levels for human and animal uses. Cyanobacteria are widely distributed in aquatic environments and can bioaccumulate arsenic (As). This study presents the response of indigenous cyanobacteria to As(III) and As(V), including the species Tolypothrix tenuis, Nostoc muscorum and Nostoc minutum, previously used with biotechnological purposes. As(III) resulted more toxic than As(V) in all cases, causing cell death in the range of 5-20 mg/l. T. tenuis growth was sensitive to As(V) with lethal inhibition at 625 mg/l, whereas the Noctoc species were stimulated. EC50 values found were 73.34 mg/l for N. muscorum and 989.3 mg/l for N. minutum. Batch cultures of N. minutum showed improvements in both growth parameters and photosynthetic pigment content in the presence of 1,000 mg/l As(V). Increases of 66.7%, 75.5%, 40% and 20.7% in cell productivity, chlorophyll a, total carotenoids and C-phycocyanin respectively were observed, reaching a bioaccumulated arsenic value of 37.4 μg/g at the stationary growth phase.

El contenido de arsénico de diversos cuerpos de agua de Argentina es superior a los niveles aceptados para consumo humano y animal. Las cianobacterias están ampliamente distribuidas en los ambientes acuáticos y pueden bioacumular As. Este estudio presenta la respuesta de cianobacterias autóctonas a As(III) y As(V), incluyendo las especies Tolypothrix tenuis, Nostoc muscorum y Nostoc minutum utilizadas previamente con fines biotecnológicos. As(III) resultó más tóxico que As(V) en todos los casos, causando muerte celular en el rango de 5-20 mg/l. El crecimiento de T. tenuis fue sensible a As(V) con inhibición letal a 625 mg/l. Sin embargo, las especies de Noctoc resultaron estimuladas. Los valores de EC50 encontrados fueron de 73,34 mg/l para N. muscorum y 989,3 mg/l para N. minutum. Los cultivos batch de N. minutum mostraron mejoras en los parámetros de crecimiento y en el contenido de pigmentos fotosintéticos en presencia de 1000 mg/l As(V). Los incrementos observados en productividad celular, contenido de clorofila a, carotenoides totales y C-ficocianina fueron de 66,7 %; 75,5 %; 40 % y 20,7 % respectivamente, alcanzando un valor de arsénico bioacumulado de 37,4 μg/g en la fase estacionaria.

Brazilian propolis protects Saccharomyces cerevisiae cells against oxidative stress

Propolis is a natural product widely used for humans. Due to its complex composition, a number of applications (antimicrobial, antiinflammatory, anesthetic, cytostatic and antioxidant) have been attributed to this substance. Using Saccharomyces cerevisiae as a eukaryotic model we investigated the mechanisms underlying the antioxidant effect of propolis from Guarapari against oxidative stress. Submitting a wild type (BY4741) and antioxidant deficient strains (ctt1∆, sod1∆, gsh1∆, gtt1∆ and gtt2∆) either to 15 mM menadione or to 2 mM hydrogen peroxide during 60 min, we observed that all strains, except the mutant sod1∆, acquired tolerance when previously treated with 25 µg/mL of alcoholic propolis extract. Such a treatment reduced the levels of ROS generation and of lipid peroxidation, after oxidative stress. The increase in Cu/Zn-Sod activity by propolis suggests that the protection might be acting synergistically with Cu/Zn-Sod.