Effects of nimodipine on cognitive function in patients with Alzheimer's disease / 中国基层医药

Objective:To investigate the effects of nimodipine on cognitive function in patients with Alzheimer's disease.Methods:A total of 200 patients with Alzheimer's disease who received treatment in Shuangqiao Hospital from January 2019 to January 2022 were included in this study. They were randomly divided into a control group and an observation group ( n = 100/group). The control group was treated with Donepezil. The observation group was treated with nimodipine and Donepezil. Before and 2 months after treatment, mental status and cognitive function were evaluated in each group. Results:After treatment, total response rate in the observation group was significantly higher than that in the control group [95% (95/100) vs. 81% (81/100), χ2 = 9.58, P < 0.05]. Alzheimer's disease assessment scale cognitive subscale score was significantly lower after treatment compared with before treatment in each group ( P < 0.05). Mini-mental State Examination score was significantly higher after treatment compared with before treatment in each group ( P < 0.05). Alzheimer's disease assessment scale cognitive subscale score in the observation group was significantly lower than that in the control group [(17.38 ± 1.95) points vs. (29.63 ± 3.39) points, t = -3.26, P < 0.05]. Mini-mental State Examination score in the observation group was significantly higher than that in the control group [(23.47 ± 4.59) points vs. (18.68 ± 3.91) points, t = 2.14, P < 0.05]. Conclusion:Nimodipine can improve cognitive function in patients with Alzheimer's disease.

Efficacy of Xiaoshuan Changrong Capsules combined with donepezil hydrochloride in the treatment of patients with vascular dementia and their effects on serum cytokines and oxidative stress / 中国基层医药

Objective:To investigate the efficacy of Xiaoshuan Changrong Capsules combined with donepezil hydrochloride in the treatment of patients with vascular dementia and their effects on serum cytokines and oxidative stress. Methods:A total of 102 patients with vascular dementia who received treatment in Hangzhou Seventh People's Hospital, China between January 2019 and January 2021 were included in this study. They were randomly divided into control and observation groups, with 51 patients per group. The control group was treated by oral donepezil hydrochloride. The observation group was given oral Xiaoshuan Changrong Capsules combined with oral donepezil hydrochloride. All patients were treated for 12 weeks. Efficacy was compared between the two groups. The Clinical Dementia Rating score, the Mini-Mental State Examination score, and serum levels of interleukin 6, insulin-like growth factor-1, tumor necrosis factor-α, superoxide dismutase and malondialdehyde were compared between before and after treatment. Results:Total response rate in the observation group was significantly higher than that in the control group [90.20% (46/51) vs. 70.59% (36/51), χ 2 = 6.22, P < 0.05]. At 12 weeks after treatment, the Clinical Dementia Rating score in the observation group was significantly lower than that in the control group [(1.34 ± 0.27) points vs. (1.89 ± 0.31) points, t = 9.55, P < 0.05]. At 12 weeks after treatment, the Mini-Mental State Examination score in the observation group was significantly higher than that in the control group [(25.45 ± 1.98) points vs. (22.32 ± 2.10) points, t = 7.74, P < 0.05]. At 12 weeks after treatment, interleukin-6, insulin-like growth factor-1, and tumor necrosis factor-α levels in the observation group were (31.28 ± 7.35) ng/L, (0.34 ± 0.08) ng/L and (9.46 ± 2.27) ng/L, respectively, which were significantly lower than those in the control group [(46.43 ± 6.28) ng/L, (0.48 ± 0.07) ng/L, (20.98 ± 3.56) ng/L, t = 11.19, 9.40, 19.48, all P < 0.05]. At 12 weeks after treatment, superoxide dismutase in the observation group was significantly higher than that in the control group [(98.91 ± 7.25) U/L vs. (86.59 ± 5.63) U/L, t = 9.58, P < 0.05] . At 12 weeks after treatment, malondialdehyde in the observation group was significantly lower than that in the control group [(3.25 ± 0.50) mmol/L vs. (4.81 ± 0.35) mmol/L, t = 18.25, P < 0.05]. Conclusion:Xiaoshuan Changrong Capsules combined with donepezil hydrochloride is highly effective on vascular dementia. It can reduce cellular inflammatory response and improve oxidative stress response. This study is of great innovation and science.

The acetylcholinesterase as indicative of intoxication for pesticide in farmers of conventional and organic cultivation / A acetilcolinesterase como indicativo de intoxicação por pesticidas em agricultores de cultivo convencional e orgânico

Abstract In this sense the objective of assessing the levels of pesticide poisoning in rural farmers of San Sebastian and take AL, using acetylcholinesterase enzymes Erythrocyte and plasma as biological indicator of intoxication. This is a prospective, transversal and descriptive variables analyzed were: year whose, sex, age group, education, location, condition, route of exposure. The data were acquired by collecting blood samples and socio demographic information of farmers. Was put as the determining factor the type of conventional and organic farming, and periods of drought and rainy. 56 volunteers were analyzed. The analyses were performed in the automatic biochemical Analyzer Cobas Integra 400 plus®. According to the results of the analyses, it was the largest number of individuals with reduced values of cholinesterase, specifically the Group of conventional farming, the period of greatest change index was in the rainy season, where the activity of AChE, expressive values presented in the city of São Sebastião, with 80% result of intoxicated, in the city of the foot - take, 21.73% over the same period. On analysis of the AChP, São Sebastião has obtained the highest number of contaminated with 18.75% and 30% respectively, in the District Take Foot stood between 10 and 21.73% of reduced levels of cholinesterase. This sets the organic system of cultivation, as the best alternative for prevention of future diseases, in addition to bringing quality of life for rural workers, as well as for consumers.

Resumo Nesse sentido objetivou-se avaliar os níveis de intoxicação por agrotóxicos em agricultores rurais de São Sebastião e Pé Leve - AL, utilizando as enzimas acetilcolinesterase Eritrocitária e Plasmática, como indicador biológico de intoxicação. Trata - se de um estudo prospectivo, transversal e descritivo cujas variáveis analisadas foram: ano, sexo, faixa etária, escolaridade, local, circunstância, via de exposição. Os dados foram adquiridos através da coleta das amostras de sangue e das informações sócio demográficas dos agricultores. Foi posto como fator determinante o tipo de cultivo convencional e orgânico, e os períodos de estiagem e chuvoso. Foram analisados 56 voluntários. As análises foram realizadas no analisador automático de bioquímica Cobas Integra® 400 plus. De acordo com os resultados das análises, percebeu-se maior número de indivíduos com valores diminuídos da colinesterase, especificamente no grupo de cultivo convencional, o período de maior índice de alteração foi na época chuvosa, onde a atividade da AChE, apresentou valores expressivos na cidade de São Sebastião, com resultado de 80% de intoxicados, na cidade do Pé - Leve, obteve-se 21,73% no mesmo período. Na análise da AChP, São Sebastião obteve maior número de contaminados com 18,75% e 30% respectivamente, já no Distrito Pé Leve ficou entre 10 e 21,73% de níveis diminuídos da colinesterase. Isso define o sistema orgânico de cultivo, como a melhor alternativa para prevenção de futuras patologias, além de trazer qualidade de vida para os trabalhadores rurais, como também para os consumidores.

Relación de intencionalidad en pacientes con intoxicaciones agudas por plaguicidas en un hospital de Ibagué-Colombia / Acute pesticide poisoning and its relationship with intentionality in patients from a hospital in Ibague-Colombia

Resumen Introducción: La intoxicación aguda por plaguicidas, asociada al suicidio, es un problema de salud pública cuyo estudio es primordial por los organismos estatales. Objetivo: Establecer la relación de intencionalidad en pacientes con intoxicación aguda por plaguicidas, junto a la descripción de algunas características sociodemográficas y de exposición registrados en un hospital de Ibagué desde 2013 a 2016. Materiales y métodos: Se realizó un estudio observacional descriptivo de corte transversal retrospectivo en 137 registros notificados con intoxicación aguda por plaguicida según los códigos del CIE 10. Desarrollo de análisis estadístico descriptivo y estratificado para encontrar la asociación de características con la intencionalidad de la intoxicación. Resultados: El 50% de los casos correspondían a personas menores de 20 años; el 79,6% de las intoxicaciones tenían fines suicidas y se observó que el 45% realizaron un intento de suicidio previo; un nivel educativo alto correspondió a un bajo riesgo de envenenamiento intencional [OR=0,05; IC95% (0,01-0,56); p=0,01]. Conclusiones: Es necesaria la cooperación entre las autoridades en salud e instituciones públicas para implementar medidas de control y demás estrategias que prevengan las intoxicaciones con plaguicidas, particularmente la exposición voluntaria asociada al suicidio, fenómeno creciente en esta ciudad.

Abstract Introduction: Acute pesticide poisoning associated with suicide is a public health problem that requires special attention by state agencies. Objective: To establish the relationship of patient's intent with acute pesticide poisoning and describe some sociodemographic and exposure characteristics registered by a hospital in Ibagué (Colombia), from 2013 to 2016. Materials and methods: A retrospective, cross-sectional, descriptive, observational study was conducted on 137 reports of acute pesticide poisoning that were registered according to ICD 10 codes. A descriptive and stratified statistical analysis was applied to establish the association between characteristics of poisoning intentionality. Results: 50% of the cases corresponded to people who were under 20 years of age. 79.6% of the poisonings were due to suicide attempt and 45% had had a previous attempt. A high educational level corresponded to a lower risk of intentional poisoning [OR=0.05; IC95% (0.01-0.56); p=0.01]. Conclusions: Cooperation between health care authorities and public institutions is necessary to implement measures and strategies in order to prevent acute pesticide poisoning events, especially those associated with suicide attempts, the frequency of which is growing in this city.

Association of CYP2D6 (G1934A) gene and hematological disturbances in chronic pesticide exposures

Cytochrome P450 family genes (CYPs) have common polymorphisms, which are evaluated for pesticide-inducedoxidative stress susceptibility. Variant alleles in CYP enzymes may uncover susceptibility biomarkers of environmentaltoxicity. This study aims to investigate the relationship between CYP2D6 (G1934A) gene polymorphisms and chronicpesticide exposures, and to evaluate the association between CYP2D6 (G1934A) gene polymorphism on biochemicaland hematological parameters. A cross-sectional study was carried out at a health promoting hospital, Suphan Buri,Thailand. Rice farmers and a control group (n = 50 for each) were recruited and their personal data were collected. Theirblood samples were obtained by venepuncture and drawn into plain and Ethylenediaminetetraacetic acid (EDTA) tubes.Serum cholinesterase (SChE), liver function test, kidney function test, and complete blood count were assessed usingautomatic analyzers; and CYP2D6 (G1934A) genotyping was carried out by polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP). SChE in rice farmers was significantly lower (p = 0.033), which maybe related to the use of chlorpyrifos. The genotypes were significantly different between rice farmers and the controlgroup (p = 0.0001), and the GA variant in rice farmers was more frequent. The CYP2D6 (G1934A) (rs 3892097))gene and SChE level were negatively correlated (r = −0.258, p = 0.009). However, other biochemical parameters werenot different. Blood indices, including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), andmean corpuscular hemoglobin concentration (MCHC), values of rice farmers were significantly lower than the controlgroup; and MCH, MCV, and MCHC values of the GA variant were also significantly lower than the wild type. The GAgenotype was associated with hematological toxicity of organophosphate metabolite in chronic exposures.

Parkinson′s disease with cognitive impairment / 中国实用内科杂志

Parkinson's disease(PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, evidence demonstrated that PD encompasses several non-motor disturbances as well, such as cognitive impairment. Mild cognitive impairment can be present since early stages of the disease, and characterized by impairments in several cognitive domains including executive functions, attention, and visuospatial skills, language, and memory; In advanced stages of the disease, cognitive defects can develop into dementia and there is a considerable heterogeneity in the cognitive impairments. In this review, we focus on the clinical characteristics, biomarkers, and drug and non-drug treatments of cognitive impairment in Parkinson's disease, hoping to provide help for clinical practice.

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, long-acting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility.

Trends and disparities in the use of cholinesterase inhibitors to treat Alzheimer's disease dispensed by the Brazilian public health system - 2008 to 2014: a nation-wide analysis / Tendência e desigualdade no uso de anticolinesterásicos para tratamento de doença de Alzheimer dispensados pelo sistema de saúde público do Brasil - 2008 e 2014: uma análise nacional

ABSTRACT In light of the high cost of dementia treatment, there is legislation authorizing free distribution of cholinesterase inhibitors to those suffering from Alzheimer's disease in Brazil. However, the existence of this free distribution does not guarantee adequate distribution. Objectives The present study aimed to investigate the trends of prescriptions and the coverage of Alzheimer's disease treatment using cholinesterase inhibitors from public pharmacies dispensing high-cost drugs in Brazil. Methods This was a retrospective study that collected data from the Brazilian public Unified Health System. All cholinesterase inhibitors distributed at no cost to Brazilians during the year 2014, as well as the estimated number and percentages of patients who used these medications, were evaluated and compared to data from the year 2008. Results Our estimates indicated that 9.7% of the population having dementia syndromes used cholinesterase inhibitors, as well as 16.1% of those with Alzheimer's disease in Brazil. A clear disparity was noted between the use and distribution of cholinesterase inhibitors, depending on the region in which they were found. Over time, an increase in the distribution of cholinesterase inhibitors has been noted. In 2008, that use was 12.0% whereas, in 2014, it was 16.1%, an increase of 34% in six years. Conclusion It was estimated that 16.1% of patients with Alzheimer's disease in Brazil use cholinesterase inhibitors. These values have increased and, in spite of not being satisfactory, they indicate a potential for improvement. However, there is still a significant disparity among the regions.

RESUMO Devido ao custo alto de tratamento, existe uma legislação autorizando a distribuição sem custo de anticolinesterásicos para pacientes com doença de Alzheimer no Brasil. Entretanto, a existência dessa distribuição gratuita nem sempre garante uma distribuição adequada. Objetivos O presente estudo objetiva investigar a distribuição e desigualdades no uso de anticolinesterásicos (AChE) dispensados pelo Sistema de Saúde Público do Brasil. Métodos Estudo retrospectivo que coletou dados do Sistema Único de Saúde brasileiro. Foram avaliados todos os anticolinesterásicos distribuídos sem custo no Brasil durante o ano de 2014, assim como o número estimado e a porcentagem de pacientes que usavam essa medicação. Esses dados foram comparados com o ano de 2008. Resultados Estima-se que 9,7% da população que possui síndromes demenciais usa anticolinesterásicos, assim como 16,1% dos pacientes com doença de Alzheimer. Uma clara desigualdade entre o uso e a distribuição dos anticolinesterásicos foi encontrada, variando de acordo com a região. Houve um aumento na distribuição de anticolinesterásicos ao longo do tempo. Em 2008, o uso era de 12% e, em 2014, foi de 16,1%, resultando em um aumento de 34% em 6 anos. Conclusão Estima-se que 16,1% dos pacientes com doença de Alzheimer no Brasil usam anticolinesterásicos. Esses valores tiveram um aumento e, embora ainda não sejam satisfatórios, eles indicam um potencial de melhora. Entretanto, ainda foi evidenciada uma significante desigualdade entre as regiões.

Pharmacotherapy for dementia

Dementia is a clinical syndrome characterized by a cluster of symptoms and signs that manifest as difficulties in cognitive functions such as memory, psychological and psychiatric changes, and impairments in activities of daily living. As a result of worldwide trends of population aging, dementia has had a huge impact on public health in almost all countries. Disease modification therapies for dementia have not yet been developed. However, pharmacotherapy is essential in patients with dementia to combat delays in their cognitive and functional decline. In this article, we review the current pharmacotherapy for dementia. Three acetylcholinesterase inhibitors—donepezil, rivastigmine, galantamine—and memantine are the only medications that have been approved for the treatment of dementia. We present the indications, dose recommendations, side effects, and criteria for National Health Insurance coverage in Korea of these medications for dementia treatment. Although the Ministry of Food and Drug Safety in Korea has not approved any medications for managing the behavioral and psychological symptoms of dementia, some antipsychotics and antidepressants have been studied and used clinically for those purposes. Clinicians may consider vitamin E, Ginkgo biloba extract, choline alfoscerate, or omega-3 fatty acids as additional treatment options. Non-steroid anti-inflammatory drugs, estrogen hormone therapy, and statins are not generally recommended for dementia treatment. We believe that our findings will aid clinicians in the treatment of patients with cognitive decline.

Niveles de colinesterasa sérica en caficultores del Departamento de Caldas, Colombia / Levels of serum cholinesterase in coffee growers from the Caldas Department, Colombia

RESUMEN Objetivo Determinar niveles de colinesterasa sérica en caficultores del departamento de Caldas y su asociación con factores demográficos y ocupacionales. Metodología Se realizó un estudio descriptivo, muestra de 1 098 agricultores del Alto Oriente y Centro Sur del Departamento de Caldas, por medio de una encuesta en la que se analizaron características del trabajador agrícola de tipo: sociodemográfico, ocupacional, clínicos y concentración de colinesterasa determinada con el método de Ellman. Resultados A nivel ocupacional, el 90,8 % de los agricultores refirió riesgo de exposición directa a plaguicidas. El 3,8 % de las determinaciones analíticas de colinesterasa fueron anormales, se relacionó que el 75,6 % de los agricultores preparan la mezcla del insecticida, el 22,2 % tienen una frecuencia de aplicación en el cultivo más de dos veces por semana, el 37,8 % no emplea ropa de protección durante la jornada de fumigación. El tiempo de la última aplicación fue dentro del rango de uno a diez días demostrando que a menor tiempo de aplicación del insecticida, se presenta mayor inhibición de la enzima. Los plaguicidas más reportados fueron los de tipo organofos-forado (58,6 %). Conclusiones El control de la exposición a plaguicidas se torna difícil porque la mayoría de trabajadores son de tipo informal. Se requiere fortalecer los programas de capacitación y campañas de sensibilización sobre los efectos de los plaguicidas en la salud, las medidas de higiene y seguridad en el trabajo. Los niveles bajos de colinesterasa sérica indican la absorción de una cantidad mínima de insecticidas inhibidores de la colinesterasa.(AU)

ABSTRACT Objective To determine the levels of serum cholinesterase in coffee growers from the Caldas department and its association with demographic and labor factors. Methodology A descriptive study was carried out in a sample of 1 098 farmers from the Upper East and South Center of the Caldas department, through a survey that analyzed characteristics such as sociodemographic, labor, and clinical conditions, as well as cholinesterase levels, determined by Ellman's method. Results Regarding the occupational aspect, 90.8 % of farmers reported a risk of direct exposure to pesticides. 3.8 % of the analytical determinations of cholinesterase were abnormal, which was related to the fact that 75.6 % of the farmers themselves prepare the mixture of the insecticide, 22.2 % spread the insecticide over their crops more than twice a week, and 37.8 % do not wear protective clothing during the fumigation. The last fumigation was within the range of one to ten days, revealing that the shorter the time of application of the insecticide, the greater the inhibition of the enzyme. The most frequent pesticides were organophosphates (58.6 %). Conclusions Controlling pesticide exposure is difficult because most workers are self-employed. It is necessary to strengthen training programs and awareness campaigns regarding the effect of pesticides on health, as well as health and safety measures at the workplace. Low levels of serum cholinesterase indicate the absorption of a minimal amount of cholinesterase inhibiting insecticides.(AU)

The acetylcholinesterase as indicative of intoxication for pesticide in farmers of conventional and organic cultivation

Abstract In this sense the objective of assessing the levels of pesticide poisoning in rural farmers of San Sebastian and take AL, using acetylcholinesterase enzymes Erythrocyte and plasma as biological indicator of intoxication. This is a prospective, transversal and descriptive variables analyzed were: year whose, sex, age group, education, location, condition, route of exposure. The data were acquired by collecting blood samples and socio demographic information of farmers. Was put as the determining factor the type of conventional and organic farming, and periods of drought and rainy. 56 volunteers were analyzed. The analyses were performed in the automatic biochemical Analyzer Cobas Integra 400 plus®. According to the results of the analyses, it was the largest number of individuals with reduced values of cholinesterase, specifically the Group of conventional farming, the period of greatest change index was in the rainy season, where the activity of AChE, expressive values presented in the city of São Sebastião, with 80% result of intoxicated, in the city of the foot take, 21.73% over the same period. On analysis of the AChP, São Sebastião has obtained the highest number of contaminated with 18.75% and 30% respectively, in the District Take Foot stood between 10 and 21.73% of reduced levels of cholinesterase. This sets the organic system of cultivation, as the best alternative for prevention of future diseases, in addition to bringing quality of life for rural workers, as well as for consumers.

Resumo Nesse sentido objetivou-se avaliar os níveis de intoxicação por agrotóxicos em agricultores rurais de São Sebastião e Pé Leve - AL, utilizando as enzimas acetilcolinesterase Eritrocitária e Plasmática, como indicador biológico de intoxicação. Trata - se de um estudo prospectivo, transversal e descritivo cujas variáveis analisadas foram: ano, sexo, faixa etária, escolaridade, local, circunstância, via de exposição. Os dados foram adquiridos através da coleta das amostras de sangue e das informações sócio demográficas dos agricultores. Foi posto como fator determinante o tipo de cultivo convencional e orgânico, e os períodos de estiagem e chuvoso. Foram analisados 56 voluntários. As análises foram realizadas no analisador automático de bioquímica Cobas Integra® 400 plus. De acordo com os resultados das análises, percebeu-se maior número de indivíduos com valores diminuídos da colinesterase, especificamente no grupo de cultivo convencional, o período de maior índice de alteração foi na época chuvosa, onde a atividade da AChE, apresentou valores expressivos na cidade de São Sebastião, com resultado de 80% de intoxicados, na cidade do Pé Leve, obteve-se 21,73% no mesmo período. Na análise da AChP, São Sebastião obteve maior número de contaminados com 18,75% e 30% respectivamente, já no Distrito Pé Leve ficou entre 10 e 21,73% de níveis diminuídos da colinesterase. Isso define o sistema orgânico de cultivo, como a melhor alternativa para prevenção de futuras patologias, além de trazer qualidade de vida para os trabalhadores rurais, como também para os consumidores.

Treatment and prevention of vascular cognitive impairment / 国际脑血管病杂志

The incidence of vascular cognitive impairment is increasing year by year.Its medical burden is getting worse, therefore, there is an urgent need to delay and prevent its occurrence and development.Active symptomatic treatment and targeted intervention of vascular risk factors may alleviate the progress of disease to a certain extent.This article reviews the advances in the treatment and prevention of vascular cognitive impairment.

Improvement of Visuo-spatial Function Assessed by Raven’s Colored Progressive Matrices in Dementia with Lewy Bodies by Donepezil Treatment

OBJECTIVE: Donepezil is used to improve cognitive impairment of dementia with Lewy bodies (DLB). Visuo-spatial dysfunction is a well-known symptom of DLB. Non-verbal Raven’s Colored Progressive Matrices (RCPM) were used to assess both visual perception and reasoning ability in DLB subjects treated with donepezil. METHODS: Twenty-one DLB patients (mean age, 78.7±4.5 years) were enrolled. RCPM assessment was performed at the time of starting donepezil and within one year after starting donepezil. RESULTS: There were significant improvements of RCPM in the total scores between one year donepezil treatment (p=0.013), in both Set A score (p=0.002) and Set AB score (p=0.015), but trend in the Set B score (p=0.083). CONCLUSION: Donepezil is useful for improving visuo-spatial impairment in DLB, but not for problem-solving impairment.

Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

ABSTRACT The leaves of Pycnanthus angolensis (Welw.) Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E)-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol) and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl)-11-methyl-dodecyl](E)-3-(3,4-dimethylphenyl)prop-2-enoate (named omifoate A) were isolated from the plant with IC50 of 22.26 µg/ml (AChE), 34.61 µg/ml (BuChE) and 6.51 µg/ml (AChE), 9.07 µg/ml (BuChE) respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations.

Acesso aos medicamentos para tratamento da doença de Alzheimer fornecidos pelo Sistema Único de Saúde em Minas Gerais, Brasil / Access to medicines for Alzheimer's disease provided by the Brazilian Unified National Health System in Minas Gerais State, Brazil / Acceso a los medicamentos para el tratamiento de la enfermedad de Alzheimer disponibles en el Sistema Único de Salud en Minas Gerais, Brasil

Resumo: Avaliou-se as barreiras de acesso ao tratamento da doença de Alzheimer com base nos processos administrativos de medicamentos inibidores da colinesterase (IChE), enviados à Secretaria de Estado de Saúde de Minas Gerais, Brasil, entre 2012 e 2013. Utilizando-se informações de 165 processos selecionados aleatoriamente, abordaram-se as dimensões de acesso: acessibilidade geográfica, acomodação, aceitabilidade, disponibilidade e capacidade aquisitiva. O trâmite administrativo para o fornecimento dos IChE levou em média 39 dias e foi influenciado por características do trajeto percorrido pelo usuário. A maioria dos prescritores cumpriu menos de 80% dos critérios exigidos pelo Protocolo Clínico e Diretrizes Terapêuticas (PCDT) da doença de Alzheimer. Como resultado, 38% dos processos não foram deferidos. A capacidade aquisitiva para o tratamento privado mensal com IChE foi de cerca de 21 dias de salário mínimo. Conclui-se que a burocracia do trâmite administrativo e a dificuldade de seguimento do PCDT pelos prescritores prejudicam o acesso ao tratamento da doença de Alzheimer e constituem uma grande carga para o orçamento dos pacientes.

Abstract: This study evaluated barriers to access to treatment for Alzheimer's disease based on administrative cases involving cholinesterase inhibitors (ChEIs) and submitted to the Minas Gerais State Health Secretariat in Brazil in 2012 and 2013. Drawing on data from 165 randomly selected cases, the study addressed the following dimensions of access: geographic accessibility, accommodation, acceptability, availability, and affordability. The administrative processing to supply ChEIs took an average of 39 days and was influenced by characteristics of the path taken by the user. The majority of the prescribers met less than 80% of the required criteria in the Clinical Protocol and Therapeutic Guidelines (CPTG) for Alzheimer's disease. As a result, 38% of requests for medication were denied. Private treatment with ChEIs cost the equivalent of 21 days of the monthly minimum wage. In conclusion, bureaucratic administrative procedures and prescribers' difficulty in following the CPTG hindered access to treatment of Alzheimer's disease and imposed a heavy burden on patients' pockets.

Resumen: Se evaluaron las barreras de acceso al tratamiento de la enfermedad de Alzheimer a partir de los procesos administrativos de medicamentos inhibidores de la colinesterasis (IChE), enviados a la Secretaría de Estado de Salud de Minas Gerais, Brasil, entre 2012 y 2013. Utilizando información de 165 procesos seleccionados aleatoriamente, se abordaron las dimensiones de acceso: accesibilidad geográfica, comodidad, aceptabilidad, disponibilidad y capacidad adquisitiva. El trámite administrativo para la provisión de los IChE llevó un promedio de 39 días y fue influenciado por características del trayecto recorrido por el usuario. La mayoría de los prescriptores cumplió menos de 80% de los criterios exigidos por el Protocolo Clínico y Directrices Terapéuticas (PCDT) de la enfermedad de Alzheimer. Como resultado, un 38% de los procesos no fueron concedidos. La capacidad adquisitiva para el tratamiento privado mensual con IChE fue de cerca de 21 días de salario mínimo. Se concluyó que la burocracia del trámite administrativo y la dificultad de seguimiento del PCDT por los prescriptores perjudican el acceso al tratamiento de la enfermedad de Alzheimer y constituye una gran carga económica para el bolsillo de los pacientes.

Effects Comparison of Cholinesterase Inhibitor Alone or Combined with Compound Haishe Capsule in the Treatment of Alzheimer’s Disease / 中国药房

OBJECTIVE:To observe the effects of Cholinesterase inhibitor combined with Compound haishe capsule on prog-nosis of patients with Alzheimer’s disease (AD). METHODS:210 AD patients were divided into donepezil group,rivastigmine group,galantamine group,Compound haishe capsule group,donepezil + Compound haishe capsule group,rivastigmine + Com-pound haishe capsule,and galantamine + Compound haishe capsule group,30 cases in each group according to visiting order. Donepezil group received Donepezil hydrochloride tablet 5 mg(4 weeks),po,bid;Compound haishe capsule received Compound haishe capsule 3 casuples,po,tid;donepezil + Compound haishe capsule group received Donepezil hydrochloride tablet 5 mg,po,qd + Compound haishe capsule 3 casuples,po,tid;galantamine+ Compound haishe capsule group received Rivastigmine hydrogen tartrate capsule 1.5 mg,po,bid + Compound haishe capsule 3 casuples,po,tid;galantamine+Compound haishe capsule group received Galantamine hydrobromide tablet 4 mg,po,bid+Com-pound haishe capsule 3 casuples, po, tid. The treatment course for all groups was 3 months. Mini-mental state examination (MMSE),AD dementia rating scale (ADAS-cog) and ability of daily life (ADL score) before and after treatment,and TESS score after treatment in all groups were observed,and the occurrence of ADR was observed. RESULTS:There was no statistical significance in MMSE, ADAS-cog and ADL score between 2 groups before treatment (P>0.05).After treatment, MMSE, ADAS-cog and ADL score in all groups were obviously improved;MMSE scores in ChEI combined with Compound haishe cap-sule groups were obviously higher than appropriate ChEI alone groups and Compound haishe capsule alone group,ADAS-cog and ADL scores were obviously lower than appropriate ChEI alone groups and Compound haishe capsule alone group;TESS scores in-cidence of adverse reactions in Compound haishe capsule alone group or combined with ChEI groups were obviously lower than ap-propriate ChEI alone groups and Compound haishe capsule group,the differences were statistically significant (P<0.05). CON-CLUSIONS:ChEI combined with Compound haishe capsule can effectively improve the mental state of AD patients,cognitive function and life activity,with higher safety.

Clinical Predictors for Mild Cognitive Impairment Progression in a Korean Cohort

BACKGROUND AND PURPOSE: Patients with mild cognitive impairment (MCI) and their caregivers are concerned with the likelihood and time course of progression to dementia. This study was performed to identify the clinical predictors of the MCI progression in a Korean registry, and investigated the effects of medications without evidence, frequently prescribed in clinical practice. METHODS: Using a Korean cohort that included older adults with MCI who completed at least one follow-up visit, clinical characteristics and total medical expenses including prescribed medications were compared between two groups: progressed to dementia or not. Cox proportional hazards regression analysis was conducted. RESULTS: During the mean 1.42±0.72 years, 215 (27.63%) of 778 participants progressed to dementia. The best predictors were age [hazard ratio (HR), 1.036; 95% confidence interval (CI), 1.006–1.067; p=0.018], apolipoprotein ε4 allele (HR, 2.247; 95% CI, 1.512–3.337; p<0.001), Clinical Dementia Rating scale-sum of boxes scores (HR, 1.367; 95% CI, 1.143–1.636; p=0.001), Instrumental Activities of Daily Living scores (HR, 1.035; 95% CI, 1.003–1.067; p=0.029), and lower Mini-Mental State Examination scores (HR, 0.892; 95% CI, 0.839–0.949; p<0.001). Total medical expenses were not different. CONCLUSIONS: Our data are in accordance with previous reports about clinical predictors for the progression from MCI to dementia. Total medical expenses were not different between groups with and without progression.

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.

Alterações bioquímicas e toxicológicas de agricultores familiares da região do Alto Jacuí, Rio Grande do Sul / Biochemical and toxicological changes among family farmers from the Alto Jacui region, Rio Grande do Sul state, Brazil

Objetivos: Avaliar possíveis alterações de marcadores bioquímicos e toxicológicos oriundas da exposição aos agroquímicos em trabalhadores rurais da região do Conselho Regional de Desenvolvimento Alto Jacuí, no Rio Grande do Sul. Métodos: Foram incluídos agricultores que tinham contato com pesticidas há mais de cinco anos e um grupo de indivíduos saudáveis, não expostos a agrotóxicos, recrutados na comunidade. Os agricultores foram submetidos a provas de função hepática e renal e atividade da enzima butirilcolinesterase. Foram ainda determinados os níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS), proteínas carboniladas (PCs) e glutationa reduzida (GSH), sendo os resultados destes parâmetros de estresse oxidativo comparados entre o grupo de agricultores expostos aos agrotóxicos e o grupo controle. Resultados: Participaram do estudo 106 agricultores com exposição a pesticidas e 103 indivíduos saudáveis, sem contato com agrotóxicos. Os valores obtidos para os parâmetros hepáticos e renais avaliados encontravam-se normais, enquanto a atividade da butirilcolinesterase estava diminuída. Os níveis plasmáticos dos parâmetros de estresse oxidativo dos agricultores estavam aumentados em relação ao grupo controle: TBARS 9,51 vs. 6,719 nmol MDA/mL (p=0,0422); PCs 11,78 vs. 9,23 nmol carbonil/mg proteína (p=0,0337); GSH 0,7180 vs. 0,3649 µmol GSH/mL (p<0,0001). Verificou-se que 51,62% dos agricultores utilizavam equipamentos de proteção individual, 8,06 % faziam uso eventual e 40,32 % não faziam uso de nenhum tipo de proteção. Conclusões: Os trabalhadores rurais avaliados apresentaram alterações que indicam estresse oxidativo, evidenciando a importância do monitoramento das condições de saúde dos mesmos, bem como do incentivo à utilização de equipamentos de proteção individual.

Aims: To evaluate possible changes in biochemical and toxicological markers in rural workers exposed to pesticides in the Alto Jacui region, Rio Grande do Sul, Brazil. Methods: The study included 106 farmworkers exposed to pesticides for over five years and 103 healthy individuals, not exposed to pesticides, selected from the community. The farmworkers were submitted to liver and kidney function tests and to butyrylcholinesterase measurements. The levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (PCs), and reduced glutathione (GSH) were also determined, and the results of these oxidative stress parameters were compared with the group of pesticide-exposed farmworkers and the control group. Results: The evaluated hepatic and renal parameters were within the reference values whereas butyrylcholinesterase activity was found to be low. The plasma levels of oxidative stress parameters in exposed farmworkers were higher than in the control group: TBARS 9.51 vs. 6.179 nmol MDA/mL (p=0.0422); PCs 11.78 vs. 9.23 nmol carbonyl/mg protein (p.0.0337); GSH 0.7180 vs. 0.3649 µmol GSH/mL (p<0.0001). Personal protective equipment was worn by 51.62% of the farmworkers, but 8.06% wore it occasionally, and 40.32% did not wear any protective clothing or gear. Conclusions: Rural workers presented changes that indicate oxidative stress, thus highlighting the importance of monitoring their health conditions, as well as encouraging the use of personal protective equipment.

Research progress in antidotes of nerve agents in the USA / 军事医学

Nerve agent not only inhibit acetylcholinesterase ( AChE) at an early stage, but also induce prolonged and progressive neuroinflammation and delayed neurodegeneration.Recently, the US National Institute of Health ( NIH) has sponsored some major programs of toxic mechanisms and treatment of nerve agents, which aims at the development of quick and effective treatment to acute intoxication and delayed effect.The experimentally effective new antidotes mainly include AChE-targeting drugs, broad-spectrum reactivators and scavengers, antiinflamatory and nerve protection drugs.