Phenotypic Characteristics of Zambian patients with Parkinson's Disease

Objective: To describe the phenotypic characteristics of adult Zambian patients with newly diagnosed Parkinson's disease (PD) at University Teaching Hospital (UTH).Background: The genetic basis of idiopathic Parkinson's disease is remains unknown. Little information is available regarding the genotype and phenotypic characteristics of PD among people of African origin.Methods: Subjects with PD were recruited from the neurology clinic from January 2010, through April 2011. Parkinson's disease diagnosis was established according to standard criteria. Only ethnic Zambian patients were included to the study. The disease was considered familial when one or more first to third degree relatives were affected with PD. Extensive pedigree was constructed for all familial and sporadic cases. Unrelated healthy controls (spouses, volunteers) were free of PD and other movement disorders. Genomic DNA was extracted from peripheral blood leukocytes according to standard procedures from patients and controls, respectively.Results: In total 46 patients for phenotype and 46 controls were matched with patients for age, gender, and area of residence. The mean age of patients at onset of the disease was 53.8 ±13.7years. Three patients had juvenile form PD and12 patients had early onset PD. In 31 patients the disease started after 50 years old. Tremor and bradykinesia were the most common initial symptoms. 26% had a history of first-and second-degree relatives affected with PD. Mean age were significantly lower in patients with familial PD (47.7±7.3) than sporadic disease (62,5±5.4) (p>0.001). In 8 families (66.6%) the disease had autosomal dominant and in 4 families (33.3%) autosomal recessive inheritance. Age at onset was significantly lower (27 years) in patients with autosomal recessive transmission than in patients with autosomal dominant inheritance. The disease duration was significantly longer in patients with autosomal recessive inheritance (11.2 years) than in patients with autosomal dominant inheritance (3 years).Conclusions: This study represents phenotypic description of Zambian patients with PD recruited in clinical based manner. The majority of our patients were characterized tremor-dominant or akineticrigid types of the disease. Age at onset of PD was younger as compared to European population. The disease has both autosomal dominant and autosomal recessive inheritance. The familial aggregation of PD warrant further studies of genetic and environmental risk factors n the Zambian population.Keywords: Phenotype, Parkinson's disease, Zambian adult

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The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK

Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks

Количественное определение моноаминовых нейротрансмиттеров в гомогенатах головного мозга крыс с помощью ВЭЖХ-МС/МС

Relevance. Evaluation of the effect of drugs on neurotransmitter processes is an important component of pharmacodynamic studies. The quantitative determination of monoamine neurotransmitters in the brain structures of laboratory animals is an urgent task of pharmacology and physiology.Purpose of the study. Development of a method for the quantitative determination of serotonin, dopamine, norepinephrine, histamine and epinephrine in rat brain homogenates using HPLC-MS/MS.Methods. The isolation of neurotransmitters from the brain of rats was carried out by homogenizing the biomaterial with acetonitrile and hydrochloric acid. The extraction was purified by liquid-liquid extraction with chloroform and isopropanol. Monoamines were detected using an AB Sciex QTrap 3200MD mass spectrometer, chromatography was performed using an Agilent Technologies 1260 Infinity II HPLC. Methanol and deionized water were used as eluent.Results. Sample preparation consisted of centrifugation of the resulting homogenate, drying of the supernatant in a stream of nitrogen, dissolution of the precipitate in the mobile phase, and purification of the solution using a mixture of chloroform and isopropanol. An Agilent InfinityLab Poroshell 120 EC-C18 4.6×100 mm, 2.7 μm analytical column was used to separate monoamine neurotransmitters. The total time of the chromatographic analysis was 12 minutes, the retention time of norepinephrine, epinephrine, dopamine, serotonin, histamine was 2.8; 3.2; 5.4; 7.9; and 2.2 minutes, respectively. The analytical range of the technique was 25.0–5000.0 ng/g for epinephrine, histamine, and dopamine; 5.0–5000.0 ng/g for serotonin and 50.0–5000.0 for norepinephrine. To test the technique, we analyzed monoamine neurotransmitters in the striatum of intact Wistar rats.Conclusion. The developed bioanalytical HPLC-MS/MS method for the quantitative determination of monoamine neurotransmitters in the rat brain fully complies with the validation requirements. The metrological characteristics of the technique make it possible to estimate the content of norepinephrine, epinephrine, dopamine, serotonin, and histamine in the brain structures of rats with high accuracy.Актуальность. Оценка влияния лекарственных средств на нейромедиаторные процессы является важной составляющей фармакодинамических исследований. Количественное определение моноаминовых нейротрансмиттеров в структурах головного мозга лабораторных животных является актуальной задачей фармакологии и физиологии.Цель – разработка методики количественного определения серотонина, дофамина, норэпинефрина, гистамина и эпинефрина в гомогенатах головного мозга крыс с помощью ВЭЖХ-МС/МС.Методы. Выделение нейромедиаторов из мозга крыс осуществляли путём гомогенизации биоматериала с ацетонитрилом и хлористоводородной кислотой. Очистку извлечения проводили с помощью жидкость-жидкостной экстракции с хлороформом и изопропанолом. Детектирование моноаминов осуществляли с помощью масс-спектрометра AB Sciex QTrap 3200MD, хроматографирование проводили с использованием ВЭЖХ Agilent Technologies 1260 Infinity II. В качестве элюента использовали метанол и деионизированную воду.Результаты. Пробоподготовка представляла собой центрифугирование полученного гомогената, высушивание супернатанта в токе азота, растворение осадка в подвижной фазе, очистку раствора с помощью смеси хлороформа и изопропанола. Для хроматографического разделения моноаминовых нейромедиаторов использовали аналитическую колонку Agilent InfinityLab Poroshell 120 EC-C18 4,6 × 100 мм, 2,7 мкм. Общее время хроматографического анализа составило 12 минут, время удерживания норэпинефрина, эпинефрина, дофамина, серотонина, гистамина составило 2,8; 3,2; 5,4; 7,9; и 2,2 минут, соответственно. Аналитический диапазон методики составил 25,0–5000,0 нг/г для эпинефрина, гистамина и дофамина; 5,0–5000,0 нг/г для серотонина и 50,0–5000,0 для норэпинефрина. Для апробации методики был проведён анализ моноаминовых нейромедиаторов в стриатуме интактных крыс Wistar. Заключение. Разработанная биоаналитическая ВЭЖХ-МС/МС-методика количественного определения моноаминовых нейромедиаторов в головном мозге крыс полностью соответствует валидационным требованиям. Метрологические характеристики методики позволяют с высокой точностью оценить содержание норэпинефрина, эпинефрина, дофамина, серотонина и гистамина в структурах головного мозга крыс

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

\ua9 2023, Springer Nature Limited. The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: s41531-023-00526-9 npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia