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1.
Sci Rep ; 13(1): 22968, 2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38151511

RESUMO

Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated intravascular coagulation, and their potential treatment with novel drugs. Thrombin generation is vital for these models, and an important potential therapeutic target. We investigated the thrombin generation profile of the Chacma baboon (Papio ursinus - a common pre-clinical model) including the effects of sex and ABO blood group. Thrombin generation curves, lag times, peak heights, times-to-peak, velocity indexes and Endogenous Thrombin Potentials (ETPs) of 40 adult Chacma baboons were assessed and compared with normal human plasma, using a low concentration of tissue factor (1 pM) and phospholipids. Reference intervals were calculated, and results compared between O and non-O ABO blood groups, and between males and females. Lag times of all baboons fell within the human reference interval. Most animals (n = 32; 80%) had times-to-peak above, and velocity indexes and peak heights markedly below (n = 27; 68%) the human range. However, 97.5% of baboons had an ETP above the human reference interval, indicating greater overall thrombin generation. ABO blood group had no effect, but males (n = 14; 35%) had less potent thrombin generation than females (n = 26; 65%), with significantly longer lag times (p = 0.0475), lower peak thrombin concentrations (p = 0.0203), and lower ETPs (p = 0.0238). Chacma baboons have greater overall endogenous thrombin generation potentials than humans, which is even more prominent in females. This should be considered when designing future baboon model experiments involving the haemostatic system, or when evaluating novel therapies in these animals.


Assuntos
Hemostáticos , Papio ursinus , Masculino , Animais , Feminino , Humanos , Trombina , Hemostáticos/farmacologia , Sistema ABO de Grupos Sanguíneos , Papio
2.
Clin Exp Med ; 21(4): 663-674, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33886002

RESUMO

TTP is a life-threatening disorder with limited pharmaceutical treatment options. Recently, the potential of streptokinase in the treatment of acquired TTP was demonstrated in humans in vitro, and in vivo in a mouse model. We aimed to determine the in vitro and in vivo effects of streptokinase in an established Papio ursinus model of acquired TTP. In vitro: VWF activities & multimer patterns and thromboelastograms were assessed with increasing concentrations of streptokinase. In vivo: After induction of TTP, escalating streptokinase doses (ranging from 50,000 to 900,000 IU) were administered, and the effects of streptokinase assessed on peripheral blood counts, fibrinolysis, VWF activities & multimer patterns and thromboelastograms. In an extension of the study, high-dose streptokinase (1,500,000-3,000,000 IU) was administered to another baboon. After spiking, fibrinolysis with loss of large VWF multimers was observed at [2200 IU/mL]-roughly equivalent to 1,500,000 IU. However, administration of escalating intravenous streptokinase doses had no in vivo effect on the TTP phenotype, and in vivo increases in plasmin activity were mild when compared with baseline, even at high doses. Minimal effect on VWF multimer patterns was observed but only at doses ≥ 1500,000 IU. Streptokinase is not effective in resolving TTP in a Papio ursinus model of TTP, possibly due to limited activation of the baboon fibrinolytic system. Modifications to this model, the use of alternative higher animal models, or alternative thrombolytics, should be considered to establish proof-of-concept.


Assuntos
Púrpura Trombocitopênica Trombótica , Animais , Camundongos , Papio , Papio ursinus , Estreptoquinase , Fator de von Willebrand
4.
S. Afr. med. j. (Online) ; 109(11): 876-879, 2019. tab
Artigo em Inglês | AIM (África) | ID: biblio-1271212

RESUMO

Background. Intron 22 inversion (inv22) may account for 45% of all cases of severe haemophilia A. Haemophilia A is underdiagnosed in South Africa (SA), and owing to limited resources the genotypes of most haemophilia A patients are unknown.Objectives. To screen the haemophilia A population in central SA for inv22 using two novel detection methods. Methods. We recruited 62 participants from 27 families affected by haemophilia A in Free State and Northern Cape provinces. We screened for inv22 with our previously reported conventional polymerase chain reaction (PCR) method, as well as with a newly developed real-time PCR method. Sanger sequencing was performed to confirm the PCR results. Results. With the real-time PCR method, 10 of the severe haemophilia A patients and 3 carriers tested inv22-positive. The conventional PCR method and real-time PCR results were comparable in all but one case, where the discrepancy was attributed to sample-specific degradation. Inv22 was found in 29.4% of the severe haemophilia A population and 22.2% of the potential carriers. The inv22 status of most SA haemophilia A patients is currently unknown. The 29.4% of haemophilia A patients who were positive for inv22 was lower than the expected 45%, which could indicate a more prominent mutation than inv22 in the SA population.Conclusions. The above finding needs to be confirmed by performing comprehensive factor VIII gene (F8) genotyping on the remainder of the haemophilia A patients in SA. The study contributes to genetic research in haemophilia A and lays a foundation for future research in haemophilia A genetics in SA


Assuntos
Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real , África do Sul
5.
PLoS One ; 11(6): e0157712, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27314588

RESUMO

Taro (Colocasia esculenta (L.) Schott) is widely distributed in tropical and sub-tropical areas. However, its origin, diversification and dispersal remain unclear. While taro genetic diversity has been documented at the country and regional levels in Asia and the Pacific, few reports are available from Americas and Africa where it has been introduced through human migrations. We used eleven microsatellite markers to investigate the diversity and diversification of taro accessions from nineteen countries in Asia, the Pacific, Africa and America. The highest genetic diversity and number of private alleles were observed in Asian accessions, mainly from India. While taro has been diversified in Asia and the Pacific mostly via sexual reproduction, clonal reproduction with mutation appeared predominant in African and American countries investigated. Bayesian clustering revealed a first genetic group of diploids from the Asia-Pacific region and to a second diploid-triploid group mainly from India. Admixed cultivars between the two genetic pools were also found. In West Africa, most cultivars were found to have originated from India. Only one multi-locus lineage was assigned to the Asian pool, while cultivars in Madagascar originated from India and Indonesia. The South African cultivars shared lineages with Japan. The Caribbean Islands cultivars were found to have originated from the Pacific, while in Costa Rica they were from India or admixed between Indian and Asian groups. Taro dispersal in the different areas of Africa and America is thus discussed in the light of available records of voyages and settlements.


Assuntos
Colocasia/genética , Variação Genética , Repetições de Microssatélites/genética , África , Alelos , América , Ásia
10.
Phytochemistry ; 55(1): 43-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11021643

RESUMO

The processed leaves and stems of Aspalathus linearis contain a new diastereomeric pair of the flavanones, (S)- and (R)-eriodictyol-6-C-beta-D-glucopyranoside, which is also formed via the oxidative cyclization of the dihydrochalcone, aspalathin, under conditions which mimic the fermentation process.


Assuntos
Fabaceae/metabolismo , Flavanonas , Flavonoides/metabolismo , Glucosídeos/metabolismo , Plantas Medicinais , Fermentação , Flavonoides/química , Glucosídeos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Estereoisomerismo
11.
Phytochemistry ; 53(2): 285-92, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10680185

RESUMO

Mushroom tyrosinase catalysed oxidation of three flavan-3-ols, viz. catechin, fisetinidol and mesquitol, was conducted to construct biphenyl bonds. Exposure of the flavan-3-ols to tyrosinase and subsequent trapping of the o-quinone intermediates resulted in the formation of novel flavan-3-ol derivatives, the structures of which were elucidated by mono- and two-dimensional 1H-NMR experiments. Application of the methodology resulted in the improved synthesis of the natural flavan-3-ol dimer, mesquitol-[5-->8]-catechin, previously isolated from Prosopis glandulosa.


Assuntos
Agaricales/enzimologia , Compostos de Bifenilo/metabolismo , Flavonoides/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Compostos de Bifenilo/química , Modelos Moleculares , Estrutura Molecular , Especificidade por Substrato
12.
Onderstepoort J Vet Res ; 61(3): 231-7, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7596576

RESUMO

Ovine keratoconjunctivitis was successfully reproduced in lambs under 1 year of age, in four separate transmission trials, by the use of mycoplasma isolates obtained from field outbreaks of ovine infectious keratoconjunctivitis. Mycoplasma isolates used in one of these trials, were identified as M. conjunctivae by means of immunofluorescence. Mycoplasma was isolated from approximately 87% of field cases examined. Branhamella ovis was isolated from 22% of field cases examined. No Chlamydia sp. or viruses were isolated from any of the outbreaks.


Assuntos
Ceratoconjuntivite Infecciosa/microbiologia , Infecções por Mycoplasma/veterinária , Mycoplasma/isolamento & purificação , Doenças dos Ovinos/microbiologia , Animais , Surtos de Doenças/veterinária , Ceratoconjuntivite Infecciosa/epidemiologia , Infecções por Mycoplasma/epidemiologia , Ovinos , Doenças dos Ovinos/epidemiologia
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