RESUMO
MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in MSTO1 on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic MSTO1 pathogenic variants, and we provide functional characterization from seven MSTO1-related disease patient fibroblasts. Bi-allelic loss-of-function variants in MSTO1 manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with MSTO1 mutations and further define the clinical spectrum and the natural history of MSTO1-related disease.
Assuntos
Proteínas de Ciclo Celular/genética , Doenças Cerebelares/genética , Proteínas do Citoesqueleto/genética , DNA Mitocondrial , Doenças Mitocondriais/genética , Distrofias Musculares/genética , Mutação , Adolescente , Adulto , Atrofia , Células Cultivadas , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/patologia , Doenças Cerebelares/fisiopatologia , Criança , Variações do Número de Cópias de DNA , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico por imagem , Doenças Mitocondriais/patologia , Doenças Mitocondriais/fisiopatologia , Músculos/patologia , Distrofias Musculares/diagnóstico por imagem , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Fenótipo , Adulto JovemRESUMO
This study aimed to investigate the incidence and causes of home accidents in the West Bank and Gaza Strip of Palestine. Quantitative data were collected through a field survey of a random sample of 1882 people from the West Bank and Gaza Strip, and qualitative data through 15 focus groups discussions with men and women from diverse sectors of Palestinian society, which contributed to the interpretation of some of the results more deeply. The most important result from the study was that more women's were exposed to home accidents (40.0%) than men (25.1%). The most common type of accident for both women and men was from a blunt or sharp object casing blunt trauma or puncture wound. Economic situation of the family, family size, presence of children and place of residence were significantly associated with exposure to domestic accidents. There is a need to educate the people of Palestine on the causes of home accidents and methods of prevention, to reduce it incidence.
RESUMO
This study was conducted to investigate the management aspects of medical solid waste (MSW) at primary health care centres in Nablus and Salfit governorates in the West Bank, Palestine. We interviewed 190 health care staff from primary health care centres in this area. The most frequent type of waste produced was sharps waste: only 5.3% of respondents said this was never produced. Infectious waste was the second most frequent type produced. Only 40.4% of the respondents stated that hazardous MSW was always treated. Over 80% said that non-sharps MSW was separated into its different components, but almost 20% said that sharps were not placed in special containers. We recorded a mean of 34 g of hazardous solid waste and 55 g of non-hazardous solid waste generated per outpatient per day. Staff awareness and training, separation of MSW, establishment of simple treatment facilities are the major measures suggested for improvement of the waste management practices.
RESUMO
There are few data about safety in the construction industry in Palestine. The main aim of the study was to assess worker's experiences and perceptions of safety at construction sites in Hebron and Bethlehem governorates of the West Bank. A structured questionnaire was completed through direct interviews with 349 construction workers. Of the respondents, 34.6% had experienced work-related accidents, 13.0% and 65.6% indicated that their workplace did not have a first-aid kit or trained first-aid specialist respectively, 35.8% reported that their work sites did not have safety tools and 83.7% had not received safety training. Workers perceived that awareness and training were the most frequent factor affecting workers' safety, with the foreman position having the greatest impact on the workers' safety. Greater enforcement of the current Palestinian safety laws is needed.
Assuntos
Acidentes de Trabalho/prevenção & controle , Indústria da Construção/organização & administração , Gestão da Segurança/organização & administração , Local de Trabalho/organização & administração , Adolescente , Adulto , Feminino , Primeiros Socorros , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Renda , Capacitação em Serviço , Masculino , Pessoa de Meia-Idade , Oriente Médio , Saúde Ocupacional , Ocupações , PercepçãoRESUMO
We aimed to identify bacterial pathogens/contaminants in dairy product samples collected by environmental health inspectors of the Palestinian Ministry of Health from 2001-04. A total of 722 samples of dairy products were randomly collected from different sources in Ramallah and Al-Bireh district. The percentages of unacceptable samples for the combined years were: 23.0% for total aerobic count, 21.0% for total coliforms, 15.2% for faecal coliforms, 1.0% for Staphylococcus aureus, 10.3% for moulds, 2.3% for yeasts and 14.3% for Escherichia coli. All the examined samples tested negative for Salmonella spp. Total aerobic counts rose continuously between 2001 and 2004.
Assuntos
Laticínios/microbiologia , Contaminação de Alimentos/estatística & dados numéricos , Inspeção de Alimentos/métodos , Microbiologia de Alimentos , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Enterobacteriaceae/isolamento & purificação , Escherichia coli/isolamento & purificação , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos/métodos , Manipulação de Alimentos/normas , Inspeção de Alimentos/normas , Fungos/isolamento & purificação , Política de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Oriente Médio , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Staphylococcus aureus/isolamento & purificação , Leveduras/isolamento & purificaçãoRESUMO
Safe handling of food in restaurants is a basic element in the reduction of foodborne illness. We investigated knowledge and practices about food safety by food-handlers in restaurants in Ramallah and Al-Bireh district of Palestine. A high proportion of workers in the restaurants had no previous experience in other restaurants and 63.4% had received no training on food sanitation and safety. Most of the restaurants in the refugee camps, villages and towns had only 1 worker. Restaurants lacked basic conditions for food sanitation and safety, such as hot water in most and cleaning materials in some. Many workers had poor personal hygiene practices. Training is needed for restaurant owners and staff to improve food handling practices and standards.
Assuntos
Manipulação de Alimentos , Inspeção de Alimentos , Conhecimentos, Atitudes e Prática em Saúde , Restaurantes , Gestão da Segurança/organização & administração , Adolescente , Adulto , Atitude Frente a Saúde , Escolaridade , Manipulação de Alimentos/métodos , Manipulação de Alimentos/estatística & dados numéricos , Inspeção de Alimentos/métodos , Inspeção de Alimentos/estatística & dados numéricos , Doenças Transmitidas por Alimentos/prevenção & controle , Desinfecção das Mãos , Humanos , Higiene/educação , Oriente Médio/epidemiologia , Avaliação das Necessidades , Roupa de Proteção/estatística & dados numéricos , Refugiados , Restaurantes/estatística & dados numéricos , Fumar/epidemiologia , Inquéritos e Questionários , População UrbanaRESUMO
Management of solid medical waste in healthcare centres within the private sector in Palestine was studied. This included segregation, transport, treatment and final disposal. The study found that 30% of the centres completely segregated all kinds of healthcare waste, 35.9% segregated the sharps and 27.7% segregated infectious waste. Healthcare waste was manually transported in 99% of the centres that segregate waste. Nearly 87% of the centres disposed of the waste in open dumps randomly distributed in the area. It is concluded that all stages of healthcare waste management in healthcare centres in the private sector pose a hazard to personnel working in them and also to the general public in Palestine.
Assuntos
Eliminação de Resíduos de Serviços de Saúde , Setor Privado/organização & administração , Humanos , Eliminação de Resíduos de Serviços de Saúde/métodos , Eliminação de Resíduos de Serviços de Saúde/estatística & dados numéricos , Oriente Médio , Avaliação das Necessidades/organização & administração , Saúde Ocupacional , Saúde Pública , Meios de Transporte/estatística & dados numéricosRESUMO
We investigated some of the housing conditions at Jalazone Refugee Camp and their impact on refugees' health inside the camp, especially those with respiratory symptoms and diseases. A randomized sample of 200 housing units, representing one fifth of the camp's population, was selected. Approximately half of the people in our sample were under 15 years. Overcrowding and high population density were significant. There was a statistically significant relationship between some respiratory conditions (common cold, cough, tonsillitis and ear infection) and poor housing conditions (including damp and mould), overcrowding and high population density. A radical solution for the housing problem is needed to avert further negative health impacts.
Assuntos
Nível de Saúde , Habitação Popular/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Adolescente , Adulto , Causalidade , Criança , Pré-Escolar , Aglomeração , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Características da Família , Fungos , Inquéritos Epidemiológicos , Humanos , Umidade , Lactente , Oriente Médio/epidemiologia , Ocupações/estatística & dados numéricos , Densidade Demográfica , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Estudos de Amostragem , Inquéritos e Questionários , Ventilação/estatística & dados numéricos , Gerenciamento de Resíduos/estatística & dados numéricos , Abastecimento de Água/estatística & dados numéricosRESUMO
We studied medical waste management in a Palestinian hospital in the West Bank and the role of municipality in this management. In general, "good management practices" were inadequate; there was insufficient separation between hazardous and non-hazardous wastes, an absence of necessary rules and regulations for the collection of wastes from the hospital wards and the on-site transport to a temporary storage location inside and outside the hospital and inadequate waste treatment and disposal of hospital wastes along with municipal garbage. Moreover, training of personnel was lacking and protective equipment and measures for staff were not available. No special landfills for hazardous wastes were found within the municipality.
Assuntos
Hospitais Municipais/organização & administração , Eliminação de Resíduos de Serviços de Saúde/métodos , Eliminação de Resíduos de Serviços de Saúde/normas , Benchmarking , Guias como Assunto , Política de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Capacitação em Serviço/organização & administração , Governo Local , Eliminação de Resíduos de Serviços de Saúde/estatística & dados numéricos , Oriente Médio , Avaliação das Necessidades , Recursos Humanos em Hospital/educação , Avaliação de Programas e Projetos de SaúdeRESUMO
Disposal of dental waste was investigated at 37 randomly selected clinics in Ramallah and AI-Bireh cities: 31 private practices and 6 public/NGO clinics. Dentists were interviewed regarding their disposal of different forms of dental waste. Disinfectants and X-ray processing solution were thrown down the drain. For sharps, 13.5% of dentists used puncture-resistant containers (only in the public/ NGO clinics), 45.9% discarded needles directly in the garbage after being recapped and 40.5% placed the used needles and blades in closed plastic bottles before throwing in the general garbage. Blood-soaked dressings and amalgam waste were also thrown in the garbage. While 10.75% of dentists were vaccinated against hepatitis B, 47% of the staff at private clinics were not.
Assuntos
Atitude do Pessoal de Saúde , Resíduos Odontológicos/prevenção & controle , Odontólogos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Eliminação de Resíduos de Serviços de Saúde/métodos , Instituições de Assistência Ambulatorial , Recursos Humanos em Odontologia/estatística & dados numéricos , Resíduos Odontológicos/efeitos adversos , Resíduos Odontológicos/estatística & dados numéricos , Desinfecção/métodos , Necessidades e Demandas de Serviços de Saúde , Hepatite B/prevenção & controle , Humanos , Eliminação de Resíduos de Serviços de Saúde/normas , Oriente Médio , Saúde Ocupacional/estatística & dados numéricos , Prática Privada , Inquéritos e Questionários , Serviços Urbanos de Saúde , Vacinação/estatística & dados numéricosRESUMO
Dentists, like other health professionals, are exposed to various occupational health problems, with specific ones of their own. A randomly distributed sample of 40 (42.2%) dentists working in East Jerusalem was interviewed. A questionnaire was used to detect their perception of occupational hazards. Most respondents were aware of biological hazards: 38% specifically mentioned hepatitis B virus and 13% human immunodeficiency virus. Perceived sources of stress included factors that coincided with international data, such as relationships with patients, physical strain and economic pressure, but also some specific to the Palestinian culture such as relationships with other dentists and Israeli occupation tax policy when dealing with the Arab dentists in East Jerusalem. Chemical dependency was not mentioned as a potential hazard.
Assuntos
Atitude do Pessoal de Saúde , Esgotamento Profissional/prevenção & controle , Odontólogos/psicologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional , Acidentes de Trabalho/prevenção & controle , Acidentes de Trabalho/psicologia , Adaptação Psicológica , Esgotamento Profissional/etiologia , Esgotamento Profissional/psicologia , Odontólogos/organização & administração , Ergonomia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Hepatite B/prevenção & controle , Hepatite B/transmissão , Humanos , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Relações Interprofissionais , Israel , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/prevenção & controle , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional , Fatores de Risco , Autocuidado/métodos , Autocuidado/psicologia , Inquéritos e Questionários , Impostos , População UrbanaRESUMO
Occupational hazards, exposure to blood and body fluids (BBF) accidents and safety precautions constitute an important public health issue. We assessed the prevalence and determinants of exposure to occupational hazards among nurses, and their knowledge of occupational safety precautions. In a cross-sectional study, we surveyed 332 nurses working in 4 hospitals, Nablus, West Bank, Palestine, by a questionnaire. Bivariate analysis tested the associations between ever exposure and the high likelihood of BBF exposure and the independent socio-demographic and occupational variables. Binary logistic regression analysis was used to assess the associations between the same two exposures and selected independent variables (those significant in the bivariate analysis). Prevalence of ever exposure to BBF was 51.7%, and was associated with working in private and charitable hospitals (OR 2.62, 2.68, respectively), having 4-6 family members (OR 0.52) and "nursing" being as one's top career choice at university (OR 0.48). The prevalence of high likelihood of BBF exposure was 62.2%, and was associated with working in charitable and private hospitals (OR 7.81, 2.43, respectively) and "nursing" being as one's top career choice (OR 0.57). Regarding knowledge, most respondents believed it is necessary to enact laws and regulations regarding occupational safety precautions, reported the use of sharps containers, immediate disinfection after an accident, reporting an accident, and using personal protective equipment. Nurses had adequate knowledge of the risks of their hospital work. Nevertheless, they exhibited high prevalence of exposure to BBF accidents. Future studies are needed to re-evaluate existing occupational safety guidelines in hospitals, establish monitoring and evaluation protocols for health care workers' adherence to the guidelines, and institute well-defined policies for reporting occupational injury incidents so these can be handled appropriately.
Assuntos
Competência Clínica/normas , Recursos Humanos de Enfermagem Hospitalar/normas , Gestão da Segurança/normas , Adulto , Líquidos Corporais , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Masculino , Oriente Médio , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/estatística & dados numéricos , Saúde Ocupacional/normas , Prevalência , Inquéritos e Questionários , Adulto JovemRESUMO
In vivo microdialysis combined with high performance liquid chromatography (HPLC) with electrochemical detection, was used to study the effect of MK-801 (0.1 mg/kg i.p.) on extracellular concentrations of dopamine (DA) 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), norepinephrine (NE) and DOPAC/DA ratio in intact, 6-hydroxydopamine (6-OHDA)-lesioned, DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine hydrochloride)-lesioned and reserpine-treated rats. The results revealed high basal DA (0.735+/-0.05 fmol/microl), DOPAC (195.93+/-20.18 fmol/microl) and NE (0.585+/-0.01 fmol/microl), low 5-HT (0.334+/-0.032 fmol/microl) and high DOPAC/DA ratio (265.11+/-20.73) in intact cACC. 6-OHDA alone (8 microg/2 microl) depleted DA (-66%), DOPAC (-65%), and NE (-62%). On the other hand, in desipramine (DMI)-pretreated rats, 6-OHDA induced a large depletion of DA (-94%), DOPAC (-97%) and reduced DOPAC/DA ratio (-73%), but increased NE to 142% of intact and 369% of 6-OHDA-lesioned rats. DSP4 (50 mg/kg) decreased NE (-97%), DOPAC (-75%) and DOPAC/DA ratio (-69%). Reserpine (5 mg/kg s.c.) significantly decreased DOPAC (-84%), DOPAC/DA ratio (-81%), 5-HT (-69%) and NE (-86%), but nonsignificantly increased DA. In the intact rats, MK-801 did not change DA, but increased DOPAC and DOPAC/DA ratio. In 6-OHDA-lesioned rats, MK-801 increased DA, whereas in 6-OHDA+DMI rats MK-801 additionally increased DOPAC and DOPAC/DA ratio. DSP4 and reserpine reduced the ability of MK-801 to increase DOPAC and DOPAC/DA ratio. MK-801 did not change NE concentration in dialysates collected from intact rats, but increased that from 6-OHDA+DMI-lesioned rats. In DSP4-lesioned and reserpine-treated rats, MK-801 increased NE but to a level lower than that observed in the intact rats. These results suggest that systemic administration of a low dose of MK-801, which induces profound locomotor stimulation without stereotypy, increases DOPAC and DOPAC/DA ratio in the cACC of intact rats, whereas it additionally increases the depleted DA and NE concentrations especially in 6-OHDA-lesioned rats pretreated with DMI.
Assuntos
Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Benzilaminas/toxicidade , Cromatografia Líquida de Alta Pressão , Desipramina/farmacologia , Dopamina/metabolismo , Masculino , Microdiálise , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Núcleo Accumbens/metabolismo , Oxidopamina/toxicidade , Ratos , Ratos Wistar , Reserpina/toxicidade , Serotonina/metabolismoRESUMO
In this study we investigated the effect of lesioning the noradrenergic systems on the behavioral effects of (5R, 10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5,10-imine hydrogen maleate--MK-801, in rats. The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride--DSP4 (60 mg/kg IP). MK-801 increased the locomotor activity and rearing. DSP4 significantly further increased the hyperlocomotor activity, circling (especially to the left side), sniffing, rolling, and falling that were induced by MK-801. These results showed that destruction of the noradrenergic system increased MK-801-hyperlocomotor activity, ataxia and stereotypy.
Assuntos
Adrenérgicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzilaminas/farmacologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Animais , Ataxia/induzido quimicamente , Sinergismo Farmacológico , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Comportamento Estereotipado/efeitos dos fármacosRESUMO
The mechanisms involved in haloperidol (HPD)-catalepsy in rat and the effect of antidepressants and methamphetamine (MA) were studied. HPD-catalepsy, as measured by high bar test, lasted for 6-8 min. MA, imipramine (IMP), nomifensine (NOM) and mianserin (MIAN) reduced the duration of catalepsy on IP injection. Electrolytic lesion of the caudate-putamen (CP) and nucleus accumbens (ACC) extensively reduced HPD-catalepsy. Microinjection of MA and NOM into ACC had a similar effect. In the medial amygdala and CP, only MA displayed anticataleptic activity. Zimelidine did not reduce the duration of catalepsy. These results suggest that dopaminergic systems play a key role in mediating HPD-catalepsy and the anticataleptic activity of MA and NOM.
Assuntos
Antidepressivos/farmacologia , Catalepsia/induzido quimicamente , Dopamina/fisiologia , Haloperidol/farmacologia , Metanfetamina/farmacologia , Animais , Catalepsia/fisiopatologia , Imipramina/farmacologia , Masculino , Mianserina/farmacologia , Microinjeções , Nomifensina/farmacologia , Ratos , Ratos Endogâmicos , Zimeldina/farmacologiaRESUMO
In this study, we investigated the behavioral effects of MK-801 (1-20 micrograms) injected into the posterior parts of nucleus accumbens (ACC) and caudate-putamen (CP) in rats. Interactions of diazepam (DZP, 10 micrograms), haloperidol (HPD, 2 micrograms), and scopolamine (SCOP, 10 micrograms) with 20 micrograms of MK-801 were also studied. All injections were done in 2 microliters. In ACC, MK-801 increased locomotion, rearing, and head shakes. The effect of MK-801 especially at 20 micrograms was accompanied by a motor syndrome: head weaves, circling, body rolls, and ataxia. DZP nonsignificantly reduced the locomotion but it significantly (p < 0.05) reduced head shakes, weaves, circling, and body rolls produced by MK-801. HPD reduced grooming and head shakes. SCOP potentiated MK-801 hyperlocomotion, whereas it decreased body rolls, head shakes, and weaves. In CP, MK-801 increased locomotion, but less than in ACC (p < 0.05). The effect of MK-801 was significantly increased by SCOP. MK-801 also increased grooming (reduced by HPD and increased by SCOP) and at 5-20 micrograms induced oral movements that were decreased by HPD. These results indicate that the posterior part of ACC is involved in MK-801 hyperlocomotion and motor syndromes, whereas CP is involved in mediating grooming and oral movements. Blockade of the muscarinic cholinergic receptors seems to facilitate hyperlocomotion and decrease head shakes produced by MK-801. Mechanisms influenced by DZP and HPD appear to be involved in motor syndrome and oral movement, respectively, induced by MK-801, but not in hyperlocomotion.
Assuntos
Comportamento Animal/efeitos dos fármacos , Núcleo Caudado/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Putamen/efeitos dos fármacos , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Changes in brain catecholamine content after lesioning the nucleus accumbens (ACC) and the effects of antidepressants were investigated using HPLC-ECD. ACC lesion reduced dopamine (DA) in the rostral caudate-putamen (r-CP), lateral hypothalamus (LH) and central amygdala (ACE). Imipramine (IMP) and nomifensine (NOM) increased DA in r-CP, caudal (c)-CP and basolateral amygdala. Mianserin (MIAN) and zimelidine (ZIM) increased DA only in c-CP. ACC lesion did not change DOPAC. Only IMP (in c-CP) and NOM (in r-CP and c-CP) increased DOPAC. Noradrenaline (NA) was decreased in c-CP and ACE after ACC lesion. IMP and ZIM displayed no effect on NA, while NOM increased NA in LH and frontal cortex (FC) and MIAN only in FC. These results suggest an important role for DA but not NA in the exhibition of muricide after ACC lesion, and in the antimuricide effect of antidepressants.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Agressão , Antidepressivos/farmacologia , Encéfalo/fisiologia , Dopamina/metabolismo , Norepinefrina/metabolismo , Núcleo Accumbens/fisiologia , Fenilacetatos/metabolismo , Núcleos Septais/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Imipramina/farmacologia , Masculino , Mianserina/farmacologia , Camundongos , Nomifensina/farmacologia , Ratos , Ratos Endogâmicos , Distribuição Tecidual , Zimeldina/farmacologiaRESUMO
The protective effect of moclobemide, a reversible and highly selective inhibitor of monoamine oxidase-A, against hypoxia-induced lethality was investigated in the present experiment. Moclobemide showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Hypothermia is known to protect animals from hypoxia. Moclobemide also decreased body temperature in mice; however, the hypothermic effect was unrelated to the antihypoxic effect. These results suggest that the protective effect of moclobemide in hypoxia is not due to a decrease in body temperature.
Assuntos
Anticonvulsivantes/uso terapêutico , Benzamidas/uso terapêutico , Temperatura Corporal/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Hipóxia/fisiopatologia , Masculino , Camundongos , Moclobemida , Convulsões/fisiopatologiaRESUMO
Amyloidß-protein (Aß) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. ß-sheet breaker peptides (ßSBP) decrease Aß fibrillogenesis and neurotoxicity by preventing or dissolving misfolded Aß aggregates. The present study investigated the effects of ßSBPs on Aß40-related neuropathology, memory impairment in 8-armed radial maze and expression of Aß40 in brain and serum. Aß40 was injected into amygdaloid nucleus followed 8 days later by octapeptideßSBPs 15-22, 16-23 and 17-24. Aß40 was detected not only in amygdala, but also in serum. Aß40 induced cellular changes in amygdala and additionally in hippocampus. Aß40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The ßSBPs decreased Aß40-induced pathological changes, memory impairment and Aß40 expression in serum. The ßSBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide ßSBPs corrected Aß40-induced memory impairment, and support investigation of ßSBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease.
Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Transtornos da Memória/tratamento farmacológico , Fragmentos de Peptídeos/antagonistas & inibidores , Envelhecimento/patologia , Doença de Alzheimer/sangue , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/genética , Animais , Modelos Animais de Doenças , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/fisiopatologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/genética , Ratos , Ratos Sprague-DawleyRESUMO
The effects of nomifensine (NOM) and methamphetamine (MA) on ambulation and rearing of rats in the open-field test were investigated. NOM and MA were injected i.p. into intact rats and nucleus accumbens (ACC)- and caudate-putamen (CP)-lesioned rats and infused into the ACC and CP. NOM (1-10 mg/kg, i.p.) and MA (1-5 mg/kg, i.p.) produced hyperactivity. However, NOM at 20 mg/kg, i.p. decreased the activity and induced repetitive head bobbing and squatting. Lesions of the ACC and CP increased open-field activity. However, lesion of the CP increased rearing more than lesion of the ACC. The increase in ambulation induced by NOM was inhibited by lesion of the ACC, whereas that induced by MA was inhibited by lesion of the CP. Although NOM (1-10 micrograms/2 microliters) and MA (0.5-10 micrograms/2 microliters) injections into the ACC and CP induced hyperactivity, the effect of NOM was greater after injection into the ACC, whereas the effect of MA was greater following injection into the CP. These results suggest that the ACC has a greater role in ambulation, while CP has a greater one in rearing. The present results, while they verified the significance of the ACC and CP in NOM- and MA-hyperactivity, also revealed a differential role of the ACC in NOM-hyperactivity and the CP in MA-hyperactivity.