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

Familial aggregation of stroke

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The use of biomedicine, complementary and alternative medicine, and ethno-medicine 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

Family environment and influence on children with epilepsy

Epilepsy a common, chronic childhood illness in Zambia with adverse effects not only on children with epilepsy but on parents/guardians and siblings.Epilepsy is a common, chronic childhood illness in Zambia and has adverse effects not only on children with epilepsy but on parents/guardians and siblings. In order to effectively understand and help children with epilepsy and their families, healthcare providers and advocacy groups must better understand the psychosocial, economic, and behavioural impact of epilepsy on the family unit. A series of focus group discussions involving the parents of children with epilepsy as well as youths with the condition were held in urban Lusaka and rural Mazabuka from 16th June to 9th October 2004. Key issues reported by families included parental fears regarding seizure-related injury with subsequent efforts to "protect" the child from such injuries. This negatively impacted parental work and educational opportunities, educational opportunities for the children were sometimes abbreviated to avoid school-related injury exposures and older children resented limitations placed upon them by their parents. Behavioural problems in the child with epilepsy resulted ill social conflicts for the entire household, both among family members and with the greater community. Sometimes however, where residence was well established and assistance requested, neighbours were a source of support for some families. Conflicts between the parents also occurred frequently as a result of stressors related to the additional care burden. Dual usage of traditional healers and medical clinics was generally reported with healthcare costs notably higher among healers. Despite their limitations, children with epilepsy reported many age-appropriate life ambitions.Office of Global AIDS/US Department of State

Cytopathological characteristics for provoked lesions of squamous epithelia of digestive system in animal models

Purpose of the study. Investigation of morphological characteristics of changes in the epithelium of foregut in experimental animals put under conditions of provoked carcinogenesis.Materials and methods. The method of chronic experiment on animals is applied: 40 female non-linear white rats, which are divided into 4 equal groups (n = 10). The first (I) and second (II) control groups of animals were exposed to mechanical trauma of the oral mucosa with additional application of 0.9 % NaCl solution and 1 % aqueous dimethyl sulfoxide (DMSO) solution with a frequency of 2 times a week. The third group of animals, i.e. the main group (4-NQO), was subjected to mechanical traumatization of the oral mucosa with additional application of 1 % DMSO aqueous solution containing 0.1 mg/ml of 4 nitroquinoline-N-oxide, with a frequency of 2 times a week. The fourth group of animals was intact. On the 1st, 7th, 10th, 14th day from the beginning of the experiment, and then every 14 days, cytological material was taken from the oral mucosa and stained with Papanicolaou stain. To compare the emerging changes, the histological picture of the organs of the foregut was studied.Results. Animals from the main group (4-NQO) showed a lag in body weight gain over the standard variance in the control (I and II) and intact groups. Atypical cells of indeterminate significance appeared in smears starting from 42 days of the experiment. Starting from the 56th day of the experiment, atypical cells (1–2 in the field of view), described in Bethesda terms as low-grade intraepithelial lesions, were detected in smears obtained from the main group of animals (4-NQO). Parabasal cells of the squamous epithelium with atypical large (more than 3 times compared to the reference) nuclei, anisonucleosis, with variable contours of the nuclear membrane within one cell, coarse chromatin were recognized as diagnostically significant.Conclusion. The severity of morphological changes in foregut epithelium in the direction of the precancerous state is significantly higher in the main group with prolonged exposure to carcinogenic factor, compared with the control and intact groups (р < 0.05). Thus, the effectiveness of modeling the conditions of provocation of carcinogenesis of the epithelium of the upper digestive tube in experimental animals was studied and proved by mechanical traumatization of the oral mucosa with additional application of carcinogen (4-NQO). This model of provocation of carcinogenesis will be used in the next study of neoplastic processes of the female reproductive system

Quantitative determination of monoamine neurotransmitters in rat brain homogenates using HPLC-MS/MS

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

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