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.

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)

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.

Early intervention of bone-nearby acupuncture combined with electroacupuncture on morphine tolerance in bone cancer pain rats and its effect on the expression of HDAC and MOR in dorsal root ganglia / 中国针灸

OBJECTIVE@#To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism.@*METHODS@#A total of 35 SD rats were randomized into a sham BCP group (=6), a BCP group (=7), a MT group (=7), a BNA+EA group (=8) and a shame BNA group (=7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot.@*RESULTS@#Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group (0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (<0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group (<0.05, <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (<0.01, <0.05), while the level of MOR was increased (<0.01).@*CONCLUSION@#Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.

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.

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.

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.

Involvement of intrathecal activation of MrgC receptor in pathological pain and morphine tolerance / 生理学报

Rodent MrgC receptor (Mas-related G-protein-coupled receptor subtype C) shares 65% sequence homology and similarities in terms of expression pattern and binding profile with human Mas-related gene X receptor 1 (hMrgX1). Therefore, researchers generally explore the role of hMrgX1 by studying the function of MrgC receptor. Murine MrgC receptor is uniquely expressed in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia (TG), which is closely related to the transmission process of pain. This review summarizes the analgesic effects of intrathecal activation of MrgC receptors in pathological pain and morphine tolerance.

Trait of Pain Killer Self-Administration among the Doctors Serving at General Hospitals Located in the Capital Area of the Republic of Korea

BACKGROUND: The aim of this study was to identify the painkillers preferred for self-administration by doctors working at general hospitals in the capital of the Republic of Korea.METHODS: We collected data, using a questionnaire, from 224 doctors working at secondary or tertiary hospitals in the capital of the Republic of Korea from July 1, 2017 to August 31, 2017. The questionnaire included questions on the preferred type of painkiller for each type of pain and the frequency of painkiller intake. Further, we evaluated the participants on the Likert scale to analyze the consideration and cognition of self-administration of painkillers.RESULTS: The doctors in this study tended to state the trade name of the painkillers rather than the generic name. They preferred acetaminophen for headache and nonsteroidal anti-inflammatory drugs for gastrointestinal (GI) pain, dysmenorrhea, toothache, and musculoskeletal pain. In the choice of painkiller for self-administration, they set utmost importance on the effectiveness of the medicine, followed by the potential side effects, physician's prescription, and the pharmacy's recommendation, in that order. The side effects attribute GI complications, hepatotoxicity, drug tolerance, and delayed diagnosis to painkiller use. There were some remarkable differences between surgeons and non-surgeons, men and women, and specialists and trainees in the conception of painkillers and pain control.CONCLUSION: This is the first study worldwide on the trait of the self-administration of painkillers by doctors, which can serve as a useful reference in clinical settings.

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.

Etude rétrospective de l'efficacité à long terme, la tolérance et le maintien thérapeutique du Méthotrexate en monothérapie au cours de la polyarthrite rhumatoïde

Introduction : L'objectif de cette étude est de déterminer l'efficacité et le maintien thérapeutique du méthotrexate utilisé dans le traitement de la polyarthrite rhumatoïde et de déterminer les facteurs prédictifs de sa réponse thérapeutique.Méthodes : nous avons mené une étude rétrospective au service de rhumatologie de l'hôpital Farhat Hached, sur une période de 3 ans (2008-2010), portant sur 100 patients atteints de polyarthrite rhumatoïde, selon les critères ACR 1987, et recevant le méthotrexate comme traitement de fond de 1ère intention en monothérapie. Résultats : l'évaluation du méthotrexate a été faite sur 2 ans reposant sur des paramètres clinico-biologiques et radiologiques. Une réponse EULAR a été obtenue dans 60% et 68,6% des cas respectivement à la 1ère et à la 2ème année et une rémission dans 5% des cas. L'âge jeune, la faible activité de la maladie et l'absence de syndrome inflammatoire biologique initial sont des facteurs prédictifs d'une bonne réponse au méthotrexate.Les effets secondaires ont été observés chez 44% de nos patients mais le méthotrexate n'a été arrêté définitivement que dans 16% des cas. Le maintien thérapeutique du méthotrexate en monothérapie a été de 86% et de 80% des cas respectivement à 1 et à 2 ans. Le principal facteur limitant le maintien du traitement a été la survenue d'effets secondaires:Conclusion Nos résultats indiquent que le méthotrexate reste efficace plus de 24 mois de traitement, avec un profil de toxicité acceptable

Efficacité et tolérance de Malacur® (dihydroartémisinine-pipéraquine) dans le traitement du paludisme simple à Plasmodium falciparum chez les sujets âgés de plus de 14 ans au Cameroun

Introduction: Les combinaisons thérapeutiques à base d'artémisinine sont depuis quelques années le traitement antipaludique de première intention dans une grande partie des pays endémiques. Des souches résistantes à différentes combinaisons ont été décelées en Asie du sud-est, ce qui oblige à une surveillance continuelle dans le monde entier. Matériels et méthode : Pour cela, à Yaoundé (Cameroun), a été réalisée une étude prospective,ouverte, non-randomisée pour évaluer l'efficacité clinique et parasitologique de l'association dihydroar- témisinine-pipéraquine (DHA-PQ) dans le traitement du paludisme simple à P. falciparum, chez les sujets âgés de plus de 14 ans. Résultats : Les résultats ont montré que 100% des 47 patients inclus dans cette analyse ont été libres de parasitémie dès le premier jour après la fin du traitement et les résultats se sont maintenus jusqu'à la fin du suivi, le 28ème jour. De la même manière 78,7% des patients ont été apyrétiques le jour après la première prise et 100% après les 3 jours de traitement. Aucun patient n'a montré d'évènement indésirable grave ni n'a abandonné le traitement pour cette raison. Conclusion : Les résultats confirment l'efficacité de l'association DHA-PQ comme traitement de première intention dans le traitement du paludisme non-compliqué à Plasmodium falciparum

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.

Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

OBJECTIVE: In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline. METHODS: The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. RESULTS: The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. CONCLUSION: Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline.

[ comparative analysis of effectiveness, tolorance and cost of second generation antidepressants in France]

While French authorities point to the need for rational prescribing, especially concerning psychotropic drugs, few data on the prescription of second-generation antidepressants [SGA] are synthesized for clinicians' use. Our objective is to carry out a comparative analysis of effectiveness and tolerability / acceptability of SGA. Considering the benefit/risk ratio and the cost [generic], the first-line treatment for a major depressive episode may be currently sertraline [50 mg / d]. It may however have more digestive side effects than other SSRIs [due to the serotonin action], which calls for caution while increasing doses. Fluoxetine seems relevant in treatment of negative symptoms of schizophrenia [20mg / d] and in bulimia [60 mg / d]. Fluvoxamine seems relevant in the case of sexual side effects with a previous SSRI, in treatment of anxiety disorders [it's affinity for sigma receptors may confer a specific action] and in psychotic depression. Mirtazapine may be a treatment of interest when a fast remission of depressive symptoms [especially insomnia] is warranted but its tolerance profile makes it difficult to use

Anesthetic effects of repeated dosing with propofol and vitamin C in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice.</p><p><b>METHODS</b>Forty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded.</p><p><b>RESULTS</b>Compared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01); anesthesia duration was shorter on day 3 than on day 2 in P50 + Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern.</p><p><b>CONCLUSION</b>Vitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.</p>