One case of myocardial damage caused by carbamate pesticide poisoning / 中华劳动卫生职业病杂志

The data of a patient with carbamate pesticide poisoning were analyzed. Cardiac arrest, oliguria, acute renal injury and pulmonary infection occurred during treatment. After cardiopulmonary resuscitation, tracheal intubation, CRRT, anti-infection and other symptomatic support treatment, the patient recovered and discharged. The myocardial damage caused by carbamate pesticide poisoning is easy to be ignored, and it often causes cardiac manifestations such as arrhythmia and cardiac insufficiency, and the related markers of cardiac injury, electrocardiogram and echocardiogram are also changed. Therefore, the awareness of cardiac damage caused by carbamate pesticide poisoning should be improved.

Effect of folic acid coated-crosslinked urethane-doped polyester elastomer nerve conduit on promoting the repair of long distance peripheral nerve injury in rats / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury.@*METHODS@#Thirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group.@*RESULTS@#At 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation ( P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation ( P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation ( P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation ( P<0.05). There was no significant difference between groups B and C at each time point after operation ( P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm 2, which was significantly more than that in group A [(298.33±153.12) cells/mm 2] ( t=6.139, P<0.001).@*CONCLUSION@#The fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.

Adverse effect of pre- and postnatal exposure to carbamate and pyrethroid pesticides on cognition in children at 4 and 6 years of age: A prospective study

Objective@#To determine the adverse effect of pre- and postnatal exposure to carbamate (propoxur) and pyrethroid pesticides on children's cognitive functions at 4 and 6 years of age. @*Method@#As part of a prospective cohort study among children with known pre- and postnatal exposure to propoxur and pyrethroids, children were examined at time points, 4 and 6 years, to determine the adverse effect of pesticide exposure on neurocognitive function, i.e., intelligence (IQ) using the WPPSI-III test. Pre- and postnatal pesticide exposures were measured by meconium and hair analysis, respectively, using gas chromatography-mass spectrometry (GCMS).@*Results@#Seven hundred twenty-four (724) maternal/children dyads were seen at four years and 717 at six years of age. Their mean (SD) full-scale IQ was low on average: 83.9 (10.2) at four years and 83.6 (8.6) at six years. Prenatal but not postnatal exposure to propoxur (-0.139, p=0.01) and pyrethroids (-0.097, p=0.05) were significantly correlated (negative) with full-scale IQ at four years but not at six years. The confounders that were significantly correlated to full-scale IQ at four and/or six years of age were maternal IQ, child’s weight, height, head circumference, socio-economic status, child environment, and stimulation at home (HOME) violence or abuse at home. Regression analysis of pesticides and confounders showed similar results, except for weight and head circumference.@*Conclusion@#We conclude that prenatal exposure to propoxur and pyrethroids had a negative effect on the children’s IQ at four years but no longer at six years. Thus, the ability of the child’s IQ to recover from the adverse effect of intrauterine pesticide insult may be attributable to the neuronal plasticity of its brain. Similarly, confounders to these outcome measures are multiple and are essential to address when evaluating the effect of pesticides on neuro-cognitive development in children.

Casuística das intoxicações por inibidores das colinesterases pelo Centro de Informação e Assistência Toxicológica do Paraná (CIATox/PR) entre 2015 e 2019 / Casuistics of poisonings by cholinesterases inhibitors by the Information and Toxicological Assistance Center of Paraná (CIATox/PR) between 2015 and 2019

Esta pesquisa buscou analisar os casos de intoxicações por organofosforados e carbamatos, presentes em agrotóxicos e pesticidas, registrados na base de dados do Centro de Informação e Assistência Toxicológica do Paraná (CIATox/PR). Trata-se de estudo retrospectivo em que foram avaliadas variáveis sociodemográficas e clínicas relacionadas à intoxicação, à forma de exposição, à causa e ao desfecho. Para a análise estatística foram utilizados testes de Kolmogorov-Smirnov, Shapiro-Wilk, Qui-Quadrado e Teste Exato de Fisher, considerando p<0,05. A amostra foi composta por 426 casos, sendo 218 (51,2%) mulheres. O principal agente foi raticida clandestino em 278 (65,2%) pacientes. A principal circunstância das intoxicações foi tentativa de suicídio com 293 (68,8%) casos. Houve predominância de exposição via oral (89,9%) e zona urbana em 349 (81,9%) casos, a maioria considerados leves (52,6%) e assistidos em serviços médicos (66,4%). Cerca de 327 (76,8%) indivíduos apresentavam manifestações clínicas. O tempo decorrido entre a exposição e o contato com o CIATox/PR foi maior nos casos considerados graves (p= 0,041). A atropina foi utilizada em 94 (49%) pacientes intoxicados por carbamatos, em 31 (33,3%) por organofosforados e em 84 (59,6%) por outros inibidores da colinesterase não especificados. Duas mulheres e um adolescente apresentaram desfecho fatal, tendo em comum a ingesta intencional de "chumbinho". A casuística predominante nesta série histórica foi paciente do sexo feminino, faixa etária adulta, residente na região metropolitana, exposta a agrotóxico por via oral, sintomática, classificada como gravidade leve, sem necessidade de atropina, contudo ocorreram três casos com desfecho para o óbito.

This research aimed to analyze the cases of poisoning by organophosphates and carbamates, present in agrochemicals and pesticides, registered in the database of the Information and Toxicological Assistance Center of Paraná (CIATox/PR). This is a retrospective study in which sociodemographic and clinical variables related to intoxication, form of exposure, cause and outcome were evaluated. For the statistical analysis, the Kolmogorov-Smirnov, Shapiro-Wilk, Chi-Square and Fisher's Exact Test were used, considering p<0.05. The sample consisted of 426 cases, 218 (51.2%) of which were women. The main agent was clandestine rodenticide in 278 (65.2%) patients. The main circumstance of intoxication was a suicide attempt with 293 (68.8%) cases. There was a predominance of oral exposure (89.9%) and urban areas in 349 (81.9%) cases, most considered mild (52.6%) and assisted in medical services (66.4%). About 327 (76.8%) individuals had clinical manifestations. The time elapsed between exposure and contact with CIATox/PR was longer in cases considered severe (p=0.041). Atropine was used in 94 (49%) patients intoxicated by carbamates, in 31 (33.3%) by organophosphates and in 84 (59.6%) by other unspecified cholinesterase inhibitors. Two women and one teenager had a fatal outcome, having in common the intentional ingestion of "chumbinho". The predominant casuistry in this historical series was a female patient, adult age, living in the metropolitan region, exposed to pesticides orally, symptomatic, classified as mild severity, without the need for atropine, however, there were three cases with an outcome of death.

A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Valores normais da atividade da colinesterase plasmática em anseriformes, com destaque para Alopochen aegyptiacus / Normal values of plasma cholinesterase activity in anseriformes, with emphasis on Alopochen aegyptiacus

A inibição da enzima colinesterase plasmática (BChE) pode ser utilizada como biomarcador para os efeitos da intoxicação por organofosforados e carbamatos. Nas aves, esta inibição ocorre de forma mais acentuada que nos mamíferos, porém poucos são os trabalhos publicados nestas espécies. O objetivo do estudo fo a dosagem da BChE em gansos-egípcios (Alopochen aegyptiacus) e nos anseriformes domésticos: gansos-domésticos (Anser anser domesticus) e marrecos (Anas platyrhynchos domesticus), para o estabelecimento de valores de referência normais. O trabalho possui ineditismo com relação à determinação desta enzima nos gansos-egípcios e domésticos. Os gansos e marrecos são mantidos em confinamento com fornecimento de alimentos e água ad libitum e em espaço adequado à sua manutenção no Instituto Adolfo Lutz (IAL), com a finalidade de fornecimento de sangue para a alimentação de triatomídeos do insetário de criação no Núcleo de Parasitoses Sistêmicas. Nos Alopochen aegyptiacus a média e o desvio padrão da BChE foram de 1.868 + 263,6 U/L, nos Anser anser domesticus 2.311 + 673,2 U/L e nos Anas platyrhynchos domesticus 4.290 + 86,11 U/L. (AU)

The inhibition of the plasma cholinesterase enzyme (BChE) can be used as a biomarker for the effects of intoxication by organophosphates and carbamates. In birds, this inhibition is more pronounced than in mammals, however there are few specific studies were conducted in this field. The aim of this study was to measure BChE in Egyptian geese (Alopochen aegyptiacus) and domestic anseriforms: domestic geese (Anser anser domesticus) and mallards (Anas platyrhynchos domesticus), not exposed to pesticides, for the establishment of normal values. The work is unprecedented regarding the determination of this enzyme in egyptian geese and domestic geese. Geese and mallards are kept in confinement with ad liditum food and water supply and in adequate space for their maintenance at the Adolfo Lutz Institute (IAL), for the purpose of supplying blood for the feeding of triatomines from the insectary of the Nucleus of Systemic Parasitoses. In Alopochen aegyptiacus the mean and standard deviation of BChE were 1,868 + 263,6 U/L, in Anser anser domesticus 2,311 + 673,2 U/L and in Anas platyrhynchos domesticus 4,290 + 86.11 U/L. (AU)

Tolerance of dark septate endophytic fungi (DSE) to 1 agrochemicals in vitro / Tolerancia de hongos endofíticos septados oscuros a agroquímicos in vitro

Abstract Dark septate endophytes (DSE) are a heterogeneous group of fungi, mostly belonging to the Phylum Ascomycota, that are involved in a mutualistic symbiosis with plant roots. The aim of this study is to evaluate the behavior of two strains of DSE isolated from wheat roots of two cropping areas in the province of Buenos Aires, Argentina, against some agrochemicals. Of all the isolates obtained, two strains were identified as Alternaria alternata and Cochliobolus sp. These DSE were found to be tolerant to glyphosate, carbendazim and cypermethrin when evaluated at the recommended agronomic dose (AD), 2 AD and, in some cases, 10 AD. This work contributes to the study of the biology of this group of fungi and their tolerance in the presence of xenobiotics widely used in agriculture.© 2019 Asociaci´on Argentina de Microbiolog´ıa. Published by Elsevier Espa˜na, S.L.U. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/bync-nd/4.0/).

Resumen Los endófitos septados oscuros (DSE) son un grupo heterogéneo de hongos que participan de una simbiosis mutualista con raíces de plantas, perteneciendo principalmente al Phylum Ascomycota. El objetivo de este estudio fue aislar DSE de raíces de trigo proveniente de dos áreas de cultivo de la provincia de Buenos Aires y evaluar el comportamiento de dos cepas de DSE aisladas de raíces de trigo frente a algunos agroquímicos en dos áreas de cultivo de la provincia de Buenos Aires. De todos los aislamientos obtenidos se seleccionaron dos cepas que se identificaron como Alternaria alternata y Cochliobolus sp. Se encontró que estos DSE son tolerantes al glifosato, el carbendazim y la cipermetrina, evaluados a las dosis agronómicas recomendadas (AD), a 2x AD y, en algunos casos, a 10x AD. Este trabajo contribuye al conocimiento de la biología de este grupo de hongos y su tolerancia a xenobióticos ampliamente utilizados en la agricultura.

Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

Occupational Risk Factors for Prostate Cancer: A Meta-analysis

Prostate cancer is the second most common cancer in men worldwide. There are many occupational factors that have been suggested to cause prostate cancer. Our aim was to evaluate the evidence for causality by a literature review of occupational factors. We searched literature in Medline and SCOPUS from 1966 to June 30, 2015 to identify occupational risk factors for prostate cancer. The following risk factors were selected: farmers/agricultural workers, pesticides – whole group, and separately organophosphate and organochlorine pesticides, carbamates and triazines, cadmium, chromium, cutting fluids, acrylonitrile, rubber manufacturing, whole body vibration, shift work, flight personnel, ionizing radiation, and occupational physical activity. For each factor a literature search was performed and presented as meta-analysis of relative risk and heterogeneity (Q and I² index). A total of 168 original studies met the inclusion criteria with 90,688 prostate cancer cases. Significantly increased risks were observed for the following occupational exposures: pesticides (metaRR = 1.15, 95% confidence interval [CI] = 1.01–1.32; I² = 84%), and specifically group of organochlorine pesticides (meta relative risk [metaRR] = 1.08, 95% CI = 1.03–1.14; I² = 0%), chromium (metaRR = 1.19, 95% CI = 1.07–1.34; I² = 31%), shift work (metaRR = 1.25, 95% CI = 1.05–1.49; I² = 78%) and pilots (metaRR = 1.41, 95% CI = 1.02–1.94; I² = 63%) and occupational physical activity in cohort studies (metaRR = 0.87, 95% CI = 0.81–0.94; I² = 0%). The literature review supports a causal association for a few of the previously suggested factors.

Análise do impacto do uso de organofosforados e carbamatos em trabalhadores rurais de um município da região noroeste do estado do Rio Grande do Sul / Impact analysis of the use of organophosphates and carbamates rural workers of the municipality in a northwest region of Rio Grande do Sul

Anualmente milhões de agricultores são intoxicados no mundo, e destes, mais de 20 mil morrem em consequência da exposição a agrotóxicos. Intoxicações por organofosforados (OF) e carbamatos (CAR) representam as maiores ameaças à saúde dos trabalhadores rurais. Os OF e CAR atuam na inibição da enzima colinesterase, sendo assim a inibição desta mostra-se um excelente indicador da severidade da intoxicação. O objetivo deste estudo foi analisar o impacto do uso de OF e CAR em trabalhadores rurais na cidade de Mato Queimado/RS. Foi realizado um estudo transversal, prospectivo e experimental. Investigaramse 27 trabalhadores rurais expostos. Foram realizadas coletas sanguíneas e dados epidemiográficos nos meses de fevereiro e março de 2014. A atividade da colinesterase foi determinada através do método bioquímico cinético colorimétrico. A faixa etária média dos participantes foi 34,6 anos (± 8,5). A forma de contato mais prevalente foi a aplicação do produto (88,9%). O tempo médio de exposição foi de 10,7 anos. 70,4% relataram usar equipamentos de proteção individual (EPI), sendo mais frequente o uso de máscara (55,5%). A média dos valores de colinesterase para foi de 3244,45 U/I (± 345,8), níveis estes abaixo dos de referência. Através dos resultados obtidos nesta pesquisa torna-se imprescindível a utilização de meios de monitoramento biológico dos trabalhadores rurais na finalidade de prevenção e promoção da saúde.

Annually millions of rural workers are intoxicated in the world, and of these, more than 20,000 die as a result of exposure to pesticides. Intoxication by insecticides organophosphate (OF) and carbamates (CAR) represent the greatest threats to the health of rural workers. OF CAR and act on the inhibition of cholinesterase enzyme, thus inhibition of this proves to be an excellent indicator of the severity of the intoxication. The objective of this study was to analyze the impact of using OF CAR and in rural workers in the city of Mato Queimado/RS. A cross-sectional, prospective and experimental study was conducted. Twenty-three rural workers exposed were investigated. Sample collection and data demographic were conducted in February and March 2014. The cholinesterase activity was determined by biochemical kinetic colorimetric method. The average age of participants was 34.6 years (± 8.5). The most prevalent form of contact is via the application of the product (88.9%). The mean duration of exposure was 10.7 years. Still, 70.4% reported using personal protective equipment (PPE), more frequent use of mask (55.5%). The average values for cholinesterase was 3244.45 U/l (± 345.8) levels below those of the reference. The results obtained in this study are essential to use biological monitoring means of rural workers in purpose of prevention and health promotion.

Quanto custa o atraso na concessão de patentes de medicamentos para a saúde no Brasil? / How much does the backlog on drug patents cost for health in Brazil? / ¿Cuánto cuesta el atraso en las patentes de medicamentos para la salud en Brasil?

Resumo: O backlog na análise de pedidos de patentes é um problema que persiste desde a promulgação da Lei nº 9.279/1996, quando o Brasil passou a conceder patentes para medicamentos novamente. Os órgãos responsáveis pela concessão dessas patentes, Instituto Nacional da Propriedade Industrial (INPI) e Agência Nacional de Vigilância Sanitária (Anvisa), alegam motivos técnico-administrativos para justificar o atraso. No entanto, os impactos econômicos para a saúde devido à ineficiência do sistema de patentes brasileiro ainda foram pouco investigados. Assim sendo, este trabalho propõe uma metodologia para estimar o quanto as compras públicas de medicamentos são oneradas em função da morosidade na análise dos pedidos de patentes no país. Os resultados mostram que mais de R$ 14 milhões são gastos desnecessariamente anualmente pelo Governo Federal com apenas um medicamento antirretroviral por causa da extensão da vigência das patentes. Conclui-se que medidas governamentais de controle dessa situação são prementes no âmbito dos Três Poderes. Dentre elas, destacam-se a contratação de servidores para o INPI, análise dos projetos de lei que tramitam na Câmara dos Deputados e Senado Federal para a alteração da Lei da Propriedade Industrial, e julgamento das Ações Diretas de Inconstitucionalidade para a supressão do dispositivo legal que possibilita a extensão da vigência das patentes.

Abstract: The backlog in processing patent applications in Brazil has persisted since the enactment of Law 9,279/1996, when the country resumed granting patents on drugs. The agencies responsible for granting such patents, namely the Brazilian National Patent and Trademark Office (INPI) and the Brazilian National Health Surveillance Agency (Anvisa) cite technical and administrative reasons for the backlog. However, little research has focused on the economic impacts for health due to the inefficiency of the Brazilian patent system. The current study thus proposes a methodology to estimate the extent to which government procurement of medicines is burdened by the backlog in drug patent applications. According to the results, a total of more than BRL 14 million (USD 4.5 million) is spent unnecessarily per year by the Federal Government on just one antiretroviral drug due to the extension of the respective patent's life. Measures to resolve this situation are urgently needed in the three branches of government. These include hiring more staff for the INPI, analysis of bills of law under review in the two houses of the Brazilian Congress to amend the Industrial Property Law, and ruling on direct class action claims of unconstitutionality to suppress the legal mechanisms that allow extending the life of patents.

Resumen: El atraso en el procesamiento de solicitudes de patentes en Brasil ha persistido desde la promulgación de la Ley 9.279/1996, cuando el país reanudó la concesión de patentes sobre drogas. Los organismos encargados de otorgar las patentes, a saber, la Oficina Nacional de Patentes y Marcas (INPI) y la Agencia Nacional de Vigilancia Sanitaria (Anvisa), alegan motivos técnico-administrativos para justificar el retraso. Sin embargo, poca investigación se ha centrado en los impactos económicos para la salud debido a la ineficiencia del sistema brasileño de patentes. El presente estudio propone una metodología para estimar el grado en que la contratación pública de medicamentos está cargada con el atraso en las solicitudes de patente de medicamentos. De acuerdo con los resultados, el gobierno federal gasta innecesariamente un total de más de BRL 14 millones (USD 4.5 millones) por un solo medicamento antirretroviral debido a la extensión de la vida de la respectiva patente. Las medidas para resolver esta situación son urgentemente necesarias en las tres ramas del gobierno. Estos incluyen la contratación de más personal para la INPI, el análisis de los proyectos de ley en revisión en las dos cámaras del Congreso brasileño para enmendar la Ley de Propiedad Industrial, y la decisión sobre demandas de acción colectiva directa de inconstitucionalidad para suprimir los mecanismos legales que permiten extender la vida de las patentes.

Assessment of hematological parameters in workers exposed to organophosphorus pesticides, carbamates and pyrethroids in Cundinamarca 2016-2017 / Evaluación de parámetros hematológicos en trabajadores expuestos a pesticidas organofosforados, carbamatos y piretroides, Cundinamarca 2016-2017

ABSTRACT Objective To establish hematotoxic alterations through clinical and paraclinical exploration in workers who are exposed to organophosphorus pesticides, carbamates and pyrethroids (OPCP) due to their work in production, packaging, distribution and fumigation processes in Cundinamarca-Colombia between 2016 and 2017. Materials and Methods A cross-sectional descriptive epidemiological study was carried out on a sample of 92 workers from six companies, mostly aged between 18 and 30 years, of which 61 % were males and 39 % females, and 71 % were workers in the operational area and 29 % in the administrative area. Univariate, bivariate and multivariate analyses were performed. Results Clinical exploration reported findings in 17 % of the sample group, of which only 2 % presented with erythrocyte cholinesterase outside the reference range. The values of hematological parameters such as peripheral blood smear (PBS) and complete blood count (CBC) were outside the range in 15 % and 47 % of the sample, respectively. Discussion The results suggest that there are hematological alterations in this group that could possibly be associated with chronic exposure to OPCP.

RESUMEN Objetivo Determinar las alteraciones hematotóxicas a través de una exploración clínica y paraclínica, en trabajadores que por su oficio se exponen a pesticidas organofosforados, carbamatos y piretroides (POCP), en procesos de producción, envase, distribución y fumigación, en el departamento de Cundinamarca Colombia. Metodología Se realizó un estudio epidemiológico descriptivo de corte transversal. Se realizó un análisis univariado, bivariado y multivariado. La muestra se conforma por 92 trabajadores de seis empresas, la mayoría entre los 18 y 30 años, de los cuales el 61 % son hombres y el 39 % mujeres, 71 % se desempeñan en el área operativa y 29 % en el área administrativa. Resultados Es de resaltar que se tienen hallazgos en la exploración clínica en el 17 % del grupo participante, solo el 2 % presenta la colinesterasa eritrocitaria por fuera del rango de referencia. Los parámetros hematológicos como el frotis de sangre periférica (FSP) presentan valores por fuera de los rangos en el 15 % y el cuadro hemático (CH) tiene valores por fuera de los rangos en el 47 % de las personas. Discusión Los resultados sugieren que existen alteraciones hematológicas en este grupo y que posiblemente podrían estar asociadas con la exposición crónica a POCP.

Actividad de butirilcolinesterasa y micronúcleos en trabajadores agrícolas expuestos a mezclas de plaguicidas / Butyrylcholinesterase activity and micronuclei in agricultural workers exposed to pesticide mixtures

Los plaguicidas son xenobióticos de gran utilidad para el control de las plagas y su uso es una realidad para obtener mayor rendimiento en los cultivos. Sin embargo, tienen el riesgo de producir toxicidad, por lo que es necesario el monitoreo biológico de los trabajadores expuestos a estas sustancias. El objetivo de este estudio fue evaluar la actividad de la butirilcolinesterasa (BCh) y la presencia de micronúcleos (MN) en trabajadores expuestos a mezclas de plaguicidas en el municipio Urdaneta, estado Lara. Participaron 82 individuos de sexo masculino, 41 expuestos (GE) y 41 no expuestos (GNE), la determinación de la butirilcolinesterasa se realizó en muestras de sangre, y la de micronúcleos en muestras epiteliales de la mucosa bucal. Los resultados fueron presentados empleando estadísticos descriptivos, frecuencias absolutas y porcentajes, utilizando el paquete libre PAST v.2.04. Los valores de actividad de BCh en el GE (3528,75+/- 1162,45U/L) mostraron diferencias estadísticamente significativas (P<0,001) en relación al GNE (5764,41+/-1641,43U/L). La frecuencia de MN presentó mayor mediana en el GE respecto al GNE (3,09 vs 0,73) con una diferencia significativa (P<0,001). Al asociar el tiempo de exposición con la actividad de BCh y la frecuencia de MN, se presentó una correlación negativa con la actividad de BCh y una correlación positiva con los MN, estadísticamente significativas P<0,001 y P<0,05. Los hallazgos obtenidos reflejan que los plaguicidas fueron utilizados en forma de mezclas siendo los más usados: organofosforados, carbamatos y piretroides produciendo modificaciones en los valores de actividad de BCh y la frecuencia de MN en individuos expuestos a plaguicidas(AU)

Pesticides are xenobiotics, useful in controlling pests and their use ileads to greater crop yields. However, they carry a risk of toxicity so biological monitoring of exposed workers is necessary. The aim of this study was to evaluate the cholinesterase activity and the presence of micronuclei in workers exposed to pesticide mixtures in the town of Urdaneta, Lara. Eighty-two workers participated, 41 exposed (EG) and 41 nonexposed (NEG), all of whome were male. Blood samples were obtained for the determination of butyrylcholinesterase (BCh); buccal mucosal epithelial samples were obtained for micronuclei (MN) sampline. The results were presented as descriptive statistics, absolute frequencies and percentages, using the PAST v.2.04 a free online software package. The BCh activity values in the EG (3528.75+/-1162.45U/L) showed statistically significant differences (P<0.001) in relation to the UEG (5764.41 +/- 1641.43U/L). Median MN frequency was highest in the EG compared to UEG (3.09vs 0.73), a significant difference (P<0.001). By associating exposure time with BCh activity and MN frequency, a negative correlation was found with BCh activity and a positive correlation with MN, both statistically significant (P<0.001 and P<0.05, respectively). The results suggested pesticide mixtures were the most often used: organophosphates, carbamates and pyrethroids produced changes in the activity values of BCh and the frequency of MN in individuals exposed to pesticides(AU)

Niveles de colinesterasa en cultivadores de papa expuestos ocupacionalmente a plaguicidas, Totoró, Cauca / Cholinesterase levels in potato growers occupationally exposed to pesticides, Totoro, Cauca

RESUMEN Introducción: El impacto en la salud que ocasiona el uso de plaguicidas en los agricultores se debe principalmente a las prácticas inadecuadas en el manejo de los mismos. Objetivo: Identificar los posibles efectos adversos en la salud y el ambiente asociados al uso y manejo de plaguicidas en el cultivo de papa. Metodología: estudio descriptivo transversal en el municipio de Totoró, departamento de Cauca (Colombia), con una muestra de 125 trabajadores. A cada individuo seleccionado se le aplicó encuesta y recolectó una muestra de 10 ml de sangre para determinar la actividad de la enzima acetilcolinesterasa tanto en plasma como en eritrocitos por la técnica de Michel. Resultados: El 74,4% (n=93) de los trabajadores empleaban plaguicidas en su trabajo y el 49,6% (n=62) los usaban en el hogar. La mayor frecuencia de uso de plaguicidas tanto en el trabajo como en el hogar está dado por los organofosforados. En relación con la determinación de la actividad de la enzima acetilcolinesterasa, el 8,0% (n=10) de los individuos presentaron inhibición de la acetilcolinesterasa eritrocitaria. Conclusiones: El mayor porcentaje de los plaguicidas empleados en el trabajo pertenecen a la categoría toxicológica III, medianamente tóxicos, seguido por la categoría I (extremadamente tóxicos). El plaguicida más frecuentemente utilizado en el trabajo fue el Manzate de categoría toxicológica III, mientras que en casa fue el Furadan (categoría toxicológica I). La inhibición de la AChE fue mínima aunque se informó del uso de plaguicidas organofosforados, carbamatos y ditiocarbamatos, entre otros.

ABSTRACT Introduction: The health impact caused by the use of pesticides on farmers is mainly due to poor practices in managing them. Objective: To identify possible adverse effects on health and the environment associated with the use and management of pesticides in potato crops. Metodology: cross sectional study in the municipality of Totoro, Cauca department (Colombia), with a sample of 125 workers. Each selected individual survey was applied and collected a sample of 10 ml of blood to determine the activity of the enzyme acetylcholinesterase both plasma and erythrocytes by Michel technique. Results: 74.4% (n = 93) of workers employed pesticides in their work and 49.6% (n = 62) used them at home. The highest frequency of pesticide use both at work and at home is given by organophosphates. Regarding the determination of the activity of the enzyme acetylcholinesterase, 8.0% (n = 10) of individuals they presented erythrocyte acetylcholinesterase inhibition. Conclusion: The highest percentage of the pesticides used at work belong to the toxicity category III, moderately toxic, followed by the category I (extremely toxic). The pesticide used most often at work was Manzate of toxicity category III, while at home was the Furadan (toxicological category I). AChE inhibition was minimal but the reported the use of organophosphates, carbamates and dithiocarbamates, among others.

Residuos de plaguicidas organofosforados y carbamatos en aguas subterráneas de bebida en las zonas rurales de Plottier y Senillosa, Patagonia Norte, Argentina / Organophosphate and carbamate pesticide residues in drinking groundwater in the rural areas of Plottier and Senillosa, North Patagonia, Argentina

Plottier y Senillosa son dos localidades contiguas que forman parte del área de producción agrícola del Alto Valle de Río Negro y Neuquén, Patagonia Norte. Entre los plaguicidas más utilizados predominan las familias de neonicotinoides, carbamatos y organofosforados. El conocimiento de los niveles de estos compuestos en aguas superficiales y subterráneas se ha convertido en un tema de interés social debido a su posible impacto en el ambiente y la salud. El objetivo del presente trabajo fue determinar niveles de residuos de plaguicidas en agua subterránea utilizada para bebida en zonas rurales de Plottier y Senillosa. Se analizaron carbamatos: propoxur, carbofuran, pirimicarb, carbaril y organofosforados: clorpirifos, dimetoato, metidation, fenaminfos, triazofos, fosmet y metil azinfos, por cromatografía gaseosa (GC), en seis sitios de muestreo, durante la época de aplicación y no aplicación de insecticidas. No se detectaron residuos de los plaguicidas estudiados por el método analítico utilizado. El límite de detección fue 0,010 µg/L para organofosforados y 0,030 µg/L para carbamatos. Estos resultados indican que las buenas prácticas agrícolas aplicadas en la zona así como las características fsicoquímicas del suelo, su espesor y el contenido de materia orgánica y las propiedades fsicoquímicas de los plaguicidas estudiados son factores que contribuyen favorablemente a la calidad del agua de bebida de la población rural.

Plottier and Senillosa are two adjoining towns that belong to the agricultural production area of Upper Valley, Río Negro and Neuquén, North Patagonia. Among the most widely used pesticides, neonicotinoids, carbamates and organophosphates are predominant. The levels of these compounds in surface and groundwater have become a topic of public concern, since the possible impact on health and environment. The aim of this study was the determination of pesticide residue levels in drinking ground-water in the rural areas of Plottier and Senillosa. Carbamates: propoxur, carbofuran, pirimicarb, carbaryl and organophosphate: chlorpyrifos, dimethoate, methidathion, fenaminfos, triazophos, phosmet, azinphos methyl, were analyzed by GC in six sampling sites during insecticide application and non-application season. No pesticide residues were detected by the analytical method used. The detection limit for organophosphates was 0.010 µg/L and 0.030 µg/L for carbamates. These results indicate that good agricultural practices, the physicochemical characteristics of the soil, its thickness, the content of organic matter and the physicochemical properties of pesticides studied are factors that positively contribute to the drinking water quality in the rural population.

Fatores associados aos óbitos entre homens envenenados por carbamato ("chumbinho") / Factores de muertes de hombres envenenados por carbamato ("chumbinho") / Factors associated with the deaths of men poisoned by carbamato ("chumbinho")

RESUMO Objetivo Determinar os fatores associados aos óbitos em vítimas de envenenamento por carbamato (“chumbinho”). Método Estudo retrospectivo, epidemiológico tipo caso-controle, baseado nas fichas de notificação de intoxicação do centro de controle de intoxicações localizado na região metropolitana do Rio de Janeiro. Foram utilizadas 24 fichas de notificação de intoxicações de homens dos 20 aos 59 anos com história de envenenamento por carbamato entre 2005 e 2009. As fichas foram sorteadas aleatoriamente, respeitando-se a razão de 1:3 (um caso para três controles). A faixa etária variou de 23 a 58 anos; a média 43,83 anos. Resultados Os sintomas mais recorrentes foram: miose (OR = 1.0; IC 95%: 0,27 – 3,69. p= 1.0), sialorreia (OR = 0,83; IC 95%: 0,22 – 3,12. p= 0,78), dispneia (OR = 0,66; IC 95%: 0.14 – 3,03. p= 0,59). Conclusão Os óbitos apresentaram associação com sialorreia, miose e dispneia e uma forte associação com estertores pulmonares, broncoespasmos e os roncos pulmonares.

RESUMEN Objetivo Determinar los factores asociados a la muerte en las víctimas de envenenamiento por carbamato (“Chumbinho”). Método Estudio retrospectivo, epidemiológico de caso y control sobre el envenenamiento en los formularios de notificación un centro de control de envenenamiento localizado en la región metropolitana de Río de Janeiro. Utilizamos 24 formularios de notificación de envenenamiento en hombres de 20 a 59 años con intoxicación por el carbamato de 2005 a 2009. Los registros fueron seleccionados al azar, respetando la proporción de 1:3 (un caso y tres controles). El rango de edad fue de 23 a 58 años, promedio de 43,83 años. Resultados Los síntomas más frecuentes fueron miosis (OR = 1,0; IC del 95%: 0,27 a 3,69 p = 1.0.), Babeo (OR = 0,83, IC 95% 0,22-3,12 p. = 0,78), disnea (OR = 0,66; IC del 95%: 0:14 - 3.03 p = 0.59). Conclusión Las muertes se asociaron con babeo, miosis y disnea, y una fuerte asociación con estertores pulmonares, broncoespasmo y el ronquido pulmonar.

ABSTRACT Objective To determine the factors associated with death in poisoning victims by carbamate (“Chumbinho”). Method Retrospective study, epidemiological case-control based on poisoning reporting forms, a poison control center located in the metropolitan region of Rio de Janeiro. We used 24 notification forms of poisoning in men aged 20 to 59 years with poisoning by carbamate history from 2005 to 2009. The records were randomly selected, respecting the ratio 1:3 (a case to three controls). The age range was 23-58 years, average 43.83 years. Results The most frequent symptoms were myosis (OR=1.0; 95% CI: 0.27 to 3.69 p=1.0.), drooling (OR=0.83; 95% CI. 0.22 to 3.12 p=0.78), and dyspnea (OR=0.66; 95% CI: 0:14-3.03 p=0.59). Conclusion The deaths were associated with drooling, miosis and dyspnea and a strong association with pulmonary rales, bronchospasm and pulmonary snoring.

Manejo actual de las intoxicaciones agudas por inhibidores de la colinesterasa: conceptos erróneos y necesidad de guías peruanas actualizadas / Current treatment of cholinesterase inhibitors poisoning: misconceptions and need for updated Peruvian guidelines

En el mundo existen millones de casos de intoxicaciones por inhibidores de la colinesterasa y miles de muertes por estas sustancias. Nuestro país no es escenario diferente. Actualmente se sigue estudiando cuáles son los regímenes más útiles y se debate algunas medidas de manejo hasta ahora muy utilizadas. La tendencia actual apunta a un tratamiento agresivo en vista que son muy raros los casos de eventos adversos severos que ponen en riesgo la vida producto del uso de fármacos como la atropina. En el Perú no hay investigación activa al respecto y solo se cuenta con una guía de manejo de intoxicaciones por organofosforados y carbamatos en niños elaborada por el Ministerio de Salud en el año 2005. Urge actualizar esta guía, ya que contiene conceptos que han cambiado en algunos casos de forma radical. El propósito de esta revisión es exponer brevemente la información actualizada más relevante sobre el manejo de estas intoxicaciones y finalmente sugerir recomendaciones para hacer modificaciones en la guía mencionada y a su vez hacer un llamado a las autoridades del Ministerio de Salud peruano para el desarrollo de una guía en adultos...

Millions of cases of cholinesterase inhibitors poisonings occur in the world and thousands of deaths by these substances are reported. Our country is not different scenario. The most useful treatment regimen is currently under research and some extensively used measures are on debate. The current trend is aggressive treatment as severe life-threatening adverse effects by drugs like atropine are very rare. In Peru there is no active research on this issue and only an organophosphate and carbamate poisoning in children treatment guide by the Ministry of Health in 2005 is available. It is urgent to update these guidelines, since they contain concepts that in some cases have radically changed due to current knowledge. The aim of this review is to briefly expose the most relevant updated information on treatment of these poisonings, to suggest evaluation of the mentioned guidelines, and to call attention of the Peruvian Ministry of Health authorities to develop guidelines for adults...

Management of exogenous intoxication by carbamates and organophosphates at an emergency unit / Manejo de intoxicação exógena por carbamatos e organofosforados em uma unidade de emergência

Summary Objectives: to evaluate and indicate the procedure to be followed in the health unit, both for diagnosis and the treatment of acute exogenous intoxications by carbamates or organophosphates. Methods: a descriptive study based on retrospective analysis of the clinical history of patients diagnosed with intoxication by carbamates or organophosphates admitted at the emergency unit of the Hospital de Urgências de Sergipe Governador João Alves (HUSE) between January and December of 2012. Some criteria were evaluated, such as: intoxicating agent; patient's age and gender; place of event, cause, circumstances and severity of the intoxication; as well as signs and symptoms of the muscarinic, nicotinic and neurological effects. Results: seventy patients (average age: 25±19.97) formed the study's population. It was observed that 77.14% of them suffered carbamate intoxication. However, organophosphate intoxications were more severe, with 68.75% of patients presenting moderate to severe forms. Suicide attempt was the leading cause of poisoning, with 62 cases (88.57% of total). Atropine administration was an effective therapeutic approach for treating signs and symptoms, which included sialorrhea (p=0.0006), nausea (p=0. 0029) and emesis (p lt0.0001). The use of activated charcoal was shown effective, both in combating the signs and symptoms presented by both patient groups (p <0.0001). Conclusion: it is concluded that the use of atropine and activated charcoal is highly effective to treat the signs and symptoms developed by patients presenting acute exogenous intoxication by carbamates or organophosphates.

Resumo Objetivo: avaliar e indicar os procedimentos a serem seguidos na unidade de saúde tanto para o diagnóstico como para o tratamento de intoxicações agudas exógenas por carbamatos ou organofosforados. Métodos: estudo descritivo baseado na análise retrospectiva da história clínica de pacientes diagnosticados com intoxicação por carbamatos ou organofosforados admitidos em uma unidade de emergência, entre janeiro e dezembro de 2012. Foram avaliados alguns critérios, como: agente intoxicador; idade do paciente e gênero; causa de envolvimento, circunstâncias e gravidade da intoxicação; sinais e sintomas dos efeitos neurológicos muscarínicos e nicotínicos. Resultados: setenta pacientes (idade média: 25±19,97 anos) formaram a população de estudo. Foi observado que 77,14% deles sofreram intoxicação por carbamatos. Os casos mais graves foram intoxicados por organofosforados, com 68,75% dos pacientes apresentando formas moderadas a graves. Tentativa de suicídio foi a causa principal de envenenamento, com 62 casos (88,57% do total). A administração de atropina foi uma medida terapêutica efetiva para tratamento de sinais e sintomas, como sialorreia (p=0,0006), náusea (p=0,0029) e êmese (p<0,0001). O uso do carvão ativado mostrou efetividade para o combate dos sinais e sintomas apresentados por pacientes em geral (p<0,0001). Conclusão: o uso de atropina e de carvão ativado é uma medida terapêutica altamente efetiva para combater os sinais e sintomas apresentados por pacientes vítimas de intoxicação aguda exógena por carbamatos ou organofosforados.

Rapid determination of 8 urinary carbamate pesticides by liquid chromatography-tandem mass spectrometry / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish a method for simultaneously determining the urinary concentrations of 8 carbamate pesticides.</p><p><b>METHODS</b>After being purified by acetonitrile precipitation, urine samples were transferred to a liquid chromatography-tandem mass spectrometry system, and the concentrations of 8 carbamate pesticides were determined by external standard method. A C18 column was used for ultra-high-performance liquid chromatography; methanol/ammonium acetate solution was used as the mobile phase for gradient elution; the mass spectrometer was operated in a multi-reaction monitoring mode.</p><p><b>RESULTS</b>The calibration curves were linear when the urinary concentrations of these carbamate pesticides were 20~800 µg/L, and the recovery rates were 61.0%~121% at spiked levels of 20, 200 and 800 µg/L, with a relative standard deviation of 1.7%~5.5%.</p><p><b>CONCLUSION</b>This determination method meets the Guide for establishing occupational health standards-part 5: Determination methods of chemicals in biological materials, and can be used for simultaneous determination of 8 carbamate pesticides in the urine of poisoning patients.</p>