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Saccharomyces cerevisiae is a unicellular organism that during the fermentative process is exposed to a variable environment; hence, resistance to multiple stress conditions is a desirable trait. The stress caused by high hydrostatic pressure (HHP) in S. cerevisiae resembles the injuries generated by other industrial stresses. In this study, it was confirmed that gene expression pattern in response to HHP displays an oxidative stress response profile which is expanded upon hydrostatic pressure release. Actually, reactive oxygen species (ROS) concentration level increased in yeast cells exposed to HHP treatment and an incubation period at room pressure led to a decrease in intracellular ROS concentration. On the other hand, ethylic, thermic and osmotic stresses did not result in any ROS accumulation in yeast cells. Microarray analysis revealed an upregulation of genes related to methionine metabolism, appearing to be a specific cellular response to HHP, and not related to other stresses, such as heat and osmotic stresses. Next, we investigated whether enhanced oxidative stress tolerance leads to enhanced tolerance to HHP stress. Overexpression of STF2 is known to enhance tolerance to oxidative stress and we show that it also leads to enhanced tolerance to HHP stress.
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Radicais Livres/metabolismo , Pressão Hidrostática , Estresse Oxidativo , Saccharomyces cerevisiae/fisiologia , Estresse Fisiológico , Perfilação da Expressão Gênica , Temperatura Alta , Análise em Microsséries , Pressão Osmótica , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos da radiaçãoRESUMO
BACKGROUND: The commercial Kalon HSV-2 IgG ELISA is currently recommended for research use in sub-Saharan Africa because of its superior accuracy compared to other serologic assays. However, there are no data on key precision parameters of Kalon such as inter-operator variation, repeatability, and reproducibility, thus contributing to a barrier for its acceptance and use in clinical trials in sub-Saharan Africa. We evaluated the analytical and field precision of the Kalon HSV-2 IgG ELISA. METHODS: A total of 600 HIV-infected and uninfected serum samples from South Africa and Zambia, previously tested by the gold standard University of Washington HSV western blot (UW-WB), were tested using Kalon by two technologists in an United States reference laboratory. Aliquots of 183 samples were retested using Kalon by an on-site technologist in a South African laboratory and a Zambian laboratory. RESULTS: Intra-assay variation was below 10 %. Intra-assay, intra-laboratory, and inter-laboratory correlation and agreement were significantly high (p < 0.01). In comparison to the UW-WB, accurate performance of Kalon was reproducible by each operator and laboratory. Receiver operating characteristic curve analysis indicated high selectivity of Kalon in the overall study population (area under the curve = 0.95, 95%CI = 0.92-0.97). DISCUSSION: Kalon is a robust assay with high precision and reproducibility. Accordingly, operator errorlikely does not contribute to the variability observed in Kalon's specificity throughout sera from sub-Saharan Africa. CONCLUSIONS: In populations with optimal diagnostic accuracy, Kalon is a reliable stand-alone method for on-site HSV-2 IgG antibody detection.
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Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Herpes Genital/diagnóstico , Herpesvirus Humano 2/imunologia , Imunoglobulina G/sangue , Laboratórios/normas , Adulto , Área Sob a Curva , Calibragem , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Infecções por HIV/complicações , Herpes Genital/complicações , Herpes Genital/virologia , Humanos , Masculino , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Devolution of healthcare services in Kenya resulted in a large number of newly recruited tuberculosis (TB) coordinators. We describe a unique collaboration between a national tuberculosis program (NTP), a local, and an international non-governmental organization to build human resource capacity in TB care and prevention. METHODS: From 2016 to 2021, the Kenya Division of National Tuberculosis, Leprosy and Lung Disease Program, Centre for Health Solutions-Kenya, and the International Union Against Tuberculosis and Lung Disease developed and conducted a series of 7-day training courses. A key focus of training was the introduction of TBData4Action, an approach involving the local use of routinely available data to strengthen decision-making and support supervision. RESULTS: Implementation outcomes included training 331 (96%) coordinators out of 344, representing all 47 counties, 37 national officers and 21 other stakeholders using the country-tailored curriculum, including hands-on group work by county teams and field practicals. Thirty-five national facilitators were identified and mentored as local faculty. Training costs were reduced by 75% compared with international alternatives. CONCLUSION: The collaboration resulted in the training of the majority of the coordinators in a standardized approach to TB care. A sustainable approach to capacity building in local data use was found feasible; the model could be adapted by other NTPs.
CONTEXTE: La décentralisation des services de santé au Kenya a conduit au recrutement d'un grand nombre de nouveaux coordinateurs TB. Nous décrivons une collaboration unique entre un programme national de lutte contre la TB (NTP), une organisation non gouvernementale locale et une organisation non gouvernementale internationale visant à renforcer les capacités humaines en matière de prévention et de soins de la TB. MÉTHODES: De 2016 à 2021, la division kényane du programme national de lutte contre la tuberculose, la lèpre et les maladies respiratoires, le Centre for Health Solutions-Kenya et l'Union internationale contre la tuberculose et les maladies respiratoires ont développé et dispensé une série de formations en 7 jours. La formation mettait l'accent sur l'introduction de l'approche TBData4Action, qui promeut une utilisation locale des données disponibles en routine afin de renforcer la prise de décision et d'épauler les activités de supervision. RÉSULTATS: Les résultats de la mise en place de cette formation comprenaient la formation de 331 (96%) coordinateurs sur 344, représentant l'ensemble des 47 pays, 37 administrateurs nationaux et 21 autres acteurs formés à l'aide du programme adapté aux besoins du pays concerné (dont travail de groupe pratique par les équipes nationales et travaux pratiques sur le terrain). Trente-cinq facilitateurs nationaux ont été identifiés et formés comme enseignants locaux. Les coûts de la formation ont été réduits de 75% par rapport aux alternatives internationales. CONCLUSION: La collaboration a permis de former la majorité des coordinateurs à l'aide d'une approche standardisée de soins de la TB. Une approche durable de renforcement des capacités en matière d'utilisation des données locales s'est avérée réalisable. Ce modèle peut être adapté à d'autres NTP.
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The feasibility of joining laser metal deposited Ti6Al4V sheets using laser beam welding was investigated in this article. The additive manufactured sheets were joined using a 3 kW CW YLS-2000-TR ytterbium laser system. The mechanical properties and microstructure of the welded additive manufactured parts (AM welds) were compared with those of the wrought sheets welded using the same laser process. The welds were characterized and compared in terms of bead geometry, microhardness, tensile strength, fractography, and microstructure. The differences in characteristics are majorly found in the width of the bead and tensile strength. The bead width of AM welds appear wider than the wrought welds, and the wrought welds exhibited higher tensile strength and ductility than the AM welds.
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Soldagem , Ligas , Lasers , Resistência à Tração , Titânio/químicaRESUMO
INTRODUCTION: Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients. METHODS: We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t-test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test. RESULTS: Thirty-one ARDS patients (A: PaO2/FiO2 ≤200, 45 ± 14 years, 16 males) and 11 controls (C: 52 ± 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 ± 27.2%, C:76.7 ± 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 ± 35.2%, C:21.8 ± 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 ± 54.3 µm, C:86.4 ± 33.3 µm, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P ≤0.03). The extension of normal epithelium showed a positive correlation with PaO2/FiO2 (r2 = 0.34; P = 0.02) and a negative correlation with plateau pressure (r2 = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r2 = 0.27; P = 0.04). CONCLUSIONS: Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.
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Remodelação das Vias Aéreas/fisiologia , Pulmão/patologia , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Autopsia , Estudos de Casos e Controles , Matriz Extracelular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Hunter syndrome, or mucopolysaccharidosis type 2 (MPS2), is a lysosomal storage disorder associated with the involvement of multiple organs such as the central nervous system, hepatomegaly, musculoskeletal, respiratory, cardiac, and hearing. This is due to the accumulation of glycosaminoglycans in body tissues leading to organ failure. Since the laboratories in Kenya do not screen for metabolic diseases, there is the likelihood of assumption that these patients do not exist. These first cases were referred from the eastern part of Kenya where the majority of inhabitants are from the same ethnic community. It was noted that there was increased mortality among boys below the age of 20 years, and hence, the families sought for help in the national referral and teaching hospital. The case series is meant to show that these cases exist and the majority of the patients may be dying before the diagnosis is made. There are no data on MPS2 from Kenya, and the prevalence and incidence are unknown. In this retrospective study, we present a case series of 6 Kenyan boys with MPS2 from a national referral hospital. They were part of 17 patients who had had their blood analyzed for metabolic diseases. All of them were symptomatic with varying degrees of central nervous system involvement. They had undetectable levels of iduronate-2-sulfatase (I2S) enzyme, and three genetic mutations were detected in the IDS gene.
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Neuroscience research in Africa remains sparse. Devising new policies to boost Africa's neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent's 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context.
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Neurociências/tendências , Publicações/tendências , África , Autoria , Internacionalidade , Fator de Impacto de Revistas , Neurociências/economia , Apoio à Pesquisa como Assunto/economiaRESUMO
We developed a model of severe allergic inflammation and investigated the impact of airway and lung parenchyma remodelling on in vivo and in vitro respiratory mechanics. BALB/c mice were sensitized and challenged with ovalbumin in severe allergic inflammation (SA) group. The control group (C) received saline using the same protocol. Light and electron microscopy showed eosinophil and neutrophil infiltration and fibrosis in airway and lung parenchyma, mucus gland hyperplasia, and airway smooth muscle hypertrophy and hyperplasia in SA group. These morphological changes led to in vivo (resistive and viscoelastic pressures, and static elastance) and in vitro (tissue elastance and resistance) lung mechanical alterations. Airway responsiveness to methacholine was markedly enhanced in SA as compared with C group. Additionally, IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid were higher in SA group. In conclusion, this model of severe allergic lung inflammation enabled us to directly assess the role of airway and lung parenchyma inflammation and remodelling on respiratory mechanics.
Assuntos
Asma/patologia , Asma/fisiopatologia , Hipersensibilidade Respiratória/patologia , Hipersensibilidade Respiratória/fisiopatologia , Mecânica Respiratória/fisiologia , Animais , Asma/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperplasia/patologia , Hipertrofia/patologia , Cloreto de Metacolina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica/métodos , Agonistas Muscarínicos/farmacologia , Músculo Liso/patologia , Músculo Liso/ultraestrutura , Ovalbumina/efeitos adversos , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Eosinofilia Pulmonar/patologia , Hipersensibilidade Respiratória/induzido quimicamente , Mecânica Respiratória/efeitos dos fármacosRESUMO
West Nile virus (WNV) is maintained in an enzootic cycle between ornithophilic mosquitoes and birds. There is paucity of information on population density of these vectors and the molecular details in Nigeria. We determined relative abundance and employed molecular methods to detect Culex species. Mosquitoes were caught from April 2013 to February 2014. Genomic DNA extraction was carried out and acetylcholinesterase 2 gene amplified by Polymerase Chain Reaction in different Culex species. Culex pipiens quinquefasciatus and Cx. p. pipiens were identified in different locations, while some other Culex species could not be identified. Culex p. quinquefasciatus were sequenced by Sanger's method. Vector density was 100 Culex species per man hour. Identification of Culex pipiens and Cx. quinquefasciatus from different locations in Ibadan, Nigeria reaffirms the presence of vectors and highlights possibility of enzootic transmission of WNV. Surveillance should be sustained in equine population and bird reservoirs.
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The transcript encoding a predominant Trypanosoma evansi variable surface glycoprotein RoTat 1.2 was cloned and expressed as a recombinant protein in Spodoptera frugiperda and Trichoplusia ni (insect) cells. Its potential as an antigen for specific detection of antibody in serum of dromedary camels affected by surra, was evaluated. In ELISA, the reactivity of the recombinant RoTat 1.2 VSG was similar to that of native RoTat 1.2 VSG. An indirect agglutination reagent was therefore prepared by coupling the recombinant RoTat 1.2 VSG onto latex particles. The performance of the latex agglutination test was evaluated on camel sera, and compared with the performance of CATT/T. evansi and LATEX/T. evansi tests, using the immune trypanolysis assay with T. evansi RoTat 1.2 as a reference test. The relative sensitivity and specificity of the latex coated with recombinant RoTat 1.2 VSG, using a 1:4 serum dilution, were respectively, 89.3 and 99.1%. No differences were observed between the performance of latex coated with recombinant RoTat 1.2 VSG and LATEX/T. evansi or CATT/T. evansi. Here, we describe the successful use of the recombinant RoTat 1.2 VSG for detection of specific antibodies induced by T. evansi infections.
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Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários , Camelus/parasitologia , Proteínas de Protozoários , Trypanosoma/imunologia , Tripanossomíase Africana/diagnóstico , Animais , Camelus/imunologia , Ensaio de Imunoadsorção Enzimática , Testes de Fixação do Látex , Valor Preditivo dos Testes , Proteínas Recombinantes , Tripanossomíase Africana/imunologiaRESUMO
BACKGROUND: Rifampicin's ability to induce hepatic enzymes is responsible for causing a clinically significant drug interaction with warfarin. Little data exists to guide clinicians on managing this interaction, especially in Sub-Saharan Africa where many patients are exposed to this combination due to a higher burden of tuberculosis. OBJECTIVE: The objective of the case series is to provide insight to practicing clinicians of the unique dynamics of this drug interaction in resource-constrained settings. The case series will provide details on commonly encountered scenarios and the dosage adjustments required to maintain a therapeutic INR. METHODS: A retrospective chart review was conducted of patients attending the Moi Teaching and Referral Hospital anticoagulation clinic in Eldoret, Kenya. Patients were included if they had a history of concurrent rifampicin and warfarin therapy and a minimum follow up of 2 months. Descriptive statistics were used to explain the demographic characteristics, time to therapeutic INR and average weekly warfarin dose. The inference on proportions test was conducted to compare the time in the therapeutic range (TTR) for patients on concurrent rifampicin to the rest of the patients not receiving rifampicin in the clinic. RESULTS: Of the 350 patient charts evaluated, 10 met the inclusion criteria. The median percentage increase of the weekly warfarin dose from baseline was 15.7%. For the patients in this analysis, the median TTR was 47%. DISCUSSION: Patients on concurrent therapy should be rigorously monitored with regular INR checks and warfarin dosage adjustments. Empiric dosage adjustments of warfarin should be avoided but patient characteristics can aid in understanding the alterations seen in INR.
Assuntos
Antibióticos Antituberculose/farmacocinética , Anticoagulantes/farmacocinética , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Varfarina/farmacocinética , Adolescente , Adulto , Idoso , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Coeficiente Internacional Normatizado , Quênia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Rifampina/administração & dosagem , Rifampina/uso terapêutico , População Rural , Tuberculose/sangue , Tuberculose/complicações , Varfarina/administração & dosagem , Varfarina/uso terapêutico , Adulto JovemRESUMO
Inflammatory bowel disease (IBD) comprises a group of idiopathic chronic intestinal inflammation syndromes that are very common in developed countries. It is characterized by intermittent episodes of clinical remission and relapse, with recurrent inflammatory injury that can lead to structural damage of the intestine. The uncontrolled intestinal immune response to bacterial antigens leads to the production of abundant cytokines and chemokines, by activated leukocytes and epithelial cells, which trigger inflammatory and oxidative reactions. The current treatment of IBD consists in long-term anti-inflammatory therapy that, however, does not exclude relapses and side effects, frequently resulting in surgical intervention. Polyphenols have been acknowledged to be anti-oxidant and anti-inflammatory and therefore, have been proposed as an alternative natural approach to prevent or treat chronic inflammatory diseases. Most studies have been in animal models of colitis, using chemical inducers or mice defective in anti-inflammatory mediators and in intestinal cell lines treated with pro-inflammatory cytokines or lipid oxidation products. These studies provide evidence that polyphenols can effectively modulate intestinal inflammation. They exert their effects by modulating cell signaling pathways, mainly activated in response to oxidative and inflammatory stimuli, and NF-kB is the principal downstream effector. Polyphenols may thus be considered able to prevent or delay the progression of IBD, especially because they reach higher concentrations in the gut than in other tissues. However, knowledge of the use of polyphenols in managing human IBD is still scanty, and further clinical studies should afford more solid evidence of their beneficial effects.
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Anti-Inflamatórios/uso terapêutico , Terapias Complementares , Doenças Inflamatórias Intestinais/tratamento farmacológico , Polifenóis/uso terapêutico , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Citocinas/metabolismo , Suplementos Nutricionais , Flavonoides/química , Flavonoides/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Mucosa Intestinal/metabolismo , Lignanas/química , Lignanas/uso terapêutico , NF-kappa B/fisiologia , Polifenóis/química , Estilbenos/química , Estilbenos/uso terapêuticoRESUMO
Anthropometric measurements such as cranial and facial forms provide essential information that can be used added provide in orofacial surgery and in diagnostic comprehension between patient and normal populations. There is no published literature about the types of head and face shapes in Fulani, Tangale and Tera ethnic groups of Nigeria. Hence, this study was undertaken to document the various cranial and facial forms of these ethnic groups residing in Gombe region of North-Eastern Nigeria. Head length, head width, head circumference, face length and face width were measured and the cephalic and prosopic indices calculated in a total of 300 subjects (150 males and 150 females). Results analyzed placed all males of the three ethnic groups in dolicocephalic head group with mean cephalic indices lower than 74.9, while all females to mesocephalic head group with mean cephalic indices between the range of 75-79.9. On the basis of face shapes, The Fulani and Tera males were found to belong to hyperleptoprosopic group, while the Tangale and Tera females to leptoprosopic group with prosopic indices over 95 and between the ranges of 90-94.9, respectively. Therefore, the findings revealed that all males and females of the three ethnic groups share close similarities in head types and some variations in face types. Furthermore, variation of head and face shapes from this study exists with those of other studies within and outside Nigeria.
Las medidas antropométricas tales como las formas craneales y faciales ofrecen importantes informaciones que son relevantes que pueden ser usadas en la cirugía orofacial y en la comprensión diagnóstica entre los pacientes y las poblaciones normales. No hay literatura publicada sobre los tipos de formas de la cabeza y la cara de los grupos étnicos Fulani, Tangale y Tera de Nigeria. Por lo tanto, este estudio se realizó para documentar las diversas formas craneales y faciales de estos grupos étnicos que residen en la región de Gombe, en el Noreste de Nigeria. Fueron medidos, longitud de la cabeza, ancho de la cabeza, circunferencia de la cabeza, longitud de la cara y ancho de la cara y se efectuaon los cálculos cefálicos y faciales en un total de 300 sujetos (150 hombres y mujeres 150). Los resultados analizados en los hombres Fulani, Tangale y Tera determinaron que éstos eran dolicocéfalos con una media de índices cefálicos menor que 74,9, mientras que las mujeres eran mesocefálicas, con índices cefálicos en el rango de 75 a 79,9. Con respecto a los tipos de cara, los hombres Fulanis y Tera se presentaron con índice prosopo en más del 95, por lo tanto, colocándolos en el grupo de cara hiperleptoprosópico, mientras que las mujeres Tangales y Tera presentaron en el índice prosopo un intervalo de 90 a 94,9, por lo tanto, colocándolas en el grupo leptoprosopo . Los resultados revelaron que los hombres y mujeres de los tres grupos étnicos comparten similitudes en los tipos de cabeza y algunas variaciones en los tipos de cara. Por otra parte, existe variación de las formas de cabeza y cara de este estudio con otros estudios realizados dentro y fuera de Nigeria.
Assuntos
Pessoa de Meia-Idade , Cabeça/anatomia & histologia , Cabeça/fisiologia , Face/anatomia & histologia , Cefalometria/métodos , Nigéria/etnologia , Pesos e MedidasRESUMO
Trypanosoma (Nannomonas) congolense comprises morphologically identical but genetically heterogeneous parasites infective to livestock and other mammalian hosts; three different genotypes of this parasite have been described previously. Restriction enzyme fragment length polymorphisms (RFLPs) in both kinetoplast DNA minicircle and nuclear DNA sequences, and randomly amplified polymorphic deoxyribonucleic acid (RAPD) patterns have been used here to demonstrate the existence of another type of T. (N.) congolense that is genotypically distinct from those that have so far been characterized at the molecular level. A highly repetitive, tandemly arranged DNA sequence and oligonucleotide primers, for use in polymerase chain reaction (PCR) amplification are described, which can be used for specific identification of the trypanosome and its distinction from others within the Nannomonas subgenus.
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Trypanosoma congolense/classificação , Animais , Sequência de Bases , Sondas de DNA/química , DNA Circular/química , DNA de Cinetoplasto , DNA de Protozoário/química , DNA Satélite/química , Éxons , Feminino , Genes de Protozoários , Quênia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido Nucleico , Trypanosoma congolense/genética , Moscas Tsé-TséRESUMO
The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ácidos e Sais Biliares/farmacologia , Ácido Tauroquenodesoxicólico/análogos & derivados , Animais , Bile/metabolismo , Ácidos e Sais Biliares/química , Fenômenos Químicos , Físico-Química , Duodeno , Infusões Intravenosas , Injeções , Masculino , Ratos , Ratos Wistar , Ácido Tauroquenodesoxicólico/química , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Tauroquenodesoxicólico/farmacologiaRESUMO
The nucleic acid probes that are currently in use detect and distinguish Trypanosoma vivax parasites according to their geographic origin. To eliminate the need for using multiple DNA probes, a study was conducted to evaluate the suitability of a tandemly reiterated sequence which encodes a T. vivax diagnostic antigen as a single probe for detection of this parasite. The antigen is recognized by monoclonal antibody Tv27 currently employed in antigen detection ELISA (Ag-ELISA). A genomic clone which contained a tetramer of the 832-bp cDNA sequence was isolated and shown to be more sensitive than the monomer. Oligonucleotide primers were designed based on the nucleotide sequence of the 832-bp cDNA insert and used in amplifying DNA sequences from the blood of cattle infected with T. vivax isolates from West Africa, Kenya, and South America. The polymerase chain reaction (PCR) product of approximately 400 bp was obtained by amplification of DNA from all the isolates studied. The oligonucleotide primers also amplified DNA sequences in T. vivax-infected tsetse flies. Subsequently, PCR was evaluated for its capacity to detect T. vivax DNA in the blood of three animals experimentally infected with the parasite. T. vivax DNA was detectable in the blood of infected animals as early as 5 days post-infection. Blood and serum samples from the three cattle and from six other infected animals were also examined for the presence of trypanosomes and T. vivax-specific diagnostic antigen. Trypanosomes appeared in the blood 7-12 days post-challenge, while the antigenemia was evident on Days 5-20 of infection. Analysis of the data obtained in the three animals during the course of infection revealed that the buffy coat technique, Ag-ELISA, and PCR revealed infection in 42, 55, and 75% of the blood samples, respectively. PCR amplification of genomic DNA of T. vivax is thus superior to the Ag-ELISA in the detection of T. vivax. More importantly, both the T. vivax diagnostic antigen and the gene encoding it are detectable in all the T. vivax isolates examined from diverse areas of Africa and South America.