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1.
Transfus Med ; 29 Suppl 1: 59-64, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30417447

RESUMO

OBJECTIVES: The aim of this research was to test a model integrating self-determination theory (SDT) and the theory of planned behaviour (TPB) to predict intention to donate blood. BACKGROUND: Social science research suggests that motivational orientations outlined by SDT can be usefully integrated with constructs from the TPB to collectively predict intention and behaviour. Such analysis has not yet been undertaken in the context of blood donation. METHODS: A total of 458 currently eligible donors completed measures of blood donor motivations, attitudes, subjective norms, perceived behavioural control (PBC) and intention. Path analyses modelled the direct and indirect effects (via TPB constructs) of motivational orientations on intention. RESULTS: SDT motivational orientations explained an additional 14% of the variance in blood donation intention, compared to a TPB-only model. Amotivation had a negative direct effect on intention; external regulation had no overall effect on intention; introjected regulation had positive direct and indirect effects on intention; and autonomous motivation predicted intention both directly as well as via attitudes, subjective norms and PBC. CONCLUSION: This research provides the first evidence that integrating SDT and the TPB is a useful approach in donor research, particularly for specifying plausible pathways through which motivational orientations impact intention to donate blood.


Assuntos
Atitude , Doadores de Sangue/psicologia , Intenção , Modelos Psicológicos , Motivação , Inquéritos e Questionários , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Zoonoses Public Health ; 64(6): 460-467, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28012251

RESUMO

In the 3 years since the first report of canine alveolar echinococcosis (AE) in Ontario, three additional cases have been diagnosed in the province. Of the four cases reported to date, three have had no known history of travel outside the province. It is possible that this development is an indication of previously unrecognized environmental contamination with Echinococcus multilocularis eggs in some areas of the province. If so, there is the potential for an emerging threat to human health. This article describes a local public health department's investigation of the possible exposure to E. multilocularis of a number of individuals who had had contact with the latest of the four cases of canine AE, and summarizes a comprehensive decision process that can be used by public health departments to assist in the follow-up of such exposures.


Assuntos
Doenças do Cão/parasitologia , Equinococose Hepática/veterinária , Echinococcus multilocularis , Saúde Pública , Animais , Anti-Helmínticos/uso terapêutico , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Cães , Equinococose , Equinococose Hepática/epidemiologia , Equinococose Hepática/prevenção & controle , Humanos , Exposição Ocupacional , Ontário/epidemiologia , Propriedade , Praziquantel/uso terapêutico , Zoonoses/prevenção & controle
3.
Clin Vaccine Immunol ; 24(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28003216

RESUMO

In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.


Assuntos
Testes Diagnósticos de Rotina/métodos , Surtos de Doenças , Caxumba/diagnóstico , Caxumba/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imunoensaio/métodos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/métodos , Vacina contra Caxumba/administração & dosagem , Ontário/epidemiologia , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto Jovem
5.
Vox Sang ; 111(3): 292-298, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27248502

RESUMO

BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25-0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.


Assuntos
Fator VIII/uso terapêutico , Fibrinogênio/uso terapêutico , Hemorragia/tratamento farmacológico , Modelos Econômicos , Transfusão de Sangue , Análise Custo-Benefício , Fator VIII/economia , Fibrinogênio/economia , Humanos , Inquéritos e Questionários
6.
Am J Transplant ; 16(8): 2483-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26913485

RESUMO

Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/imunologia , Imunoglobulinas Intravenosas/imunologia , Isoanticorpos/imunologia , Falência Renal Crônica/cirurgia , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Testes de Função Renal , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Plasmaferese , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco
7.
J Neural Eng ; 11(4): 046002, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24891494

RESUMO

OBJECTIVE: Both electrical stimuli (endogenous and exogenous) and topographical cues are instructive to axonal extension. This report, for the first time, investigated the relative dominance of directional topographical guidance cues and directional electrical cues to enhance and/or direct primary neurite extension. We hypothesized the combination of electrical stimulation with electrospun fiber topography would induce longer neurite extension from dorsal root ganglia neurons than the presence of electrical stimulation or aligned topography alone. APPROACH: To test the hypothesis, neurite outgrowth was examined on laminin-coated poly-L-lactide films or electrospun fibers (2 µm in diameter) in the presence or absence of electrical stimulation. Immunostained neurons were semi-automatically traced using Neurolucida software and morphology was evaluated. MAIN RESULTS: Neurite extension increased 74% on the aligned fibers compared to film controls. Stimulation alone increased outgrowth by 32% on films or fibers relative to unstimulated film controls. The co-presentation of topographical (fibers) with biophysical (electrical stimulation) cues resulted in a synergistic 126% increase in outgrowth relative to unstimulated film controls. Field polarity had no influence on the directionality of neurites, indicating topographical cues are responsible for guiding neurite extension. SIGNIFICANCE: Both cues (electrical stimulation and fiber geometry) are modular in nature and can be synergistically applied in conjunction with other common methods in regenerative medicine such as controlled release of growth factors to further influence axonal growth in vivo. The combined application of electrical and aligned fiber topographical guidance cues described herein, if translated in vivo, could provide a more supportive environment for directed and robust axonal regeneration following peripheral nerve injury.


Assuntos
Estimulação Elétrica , Neuritos/fisiologia , Poliésteres/química , Sinais (Psicologia) , Cultura em Câmaras de Difusão , Campos Eletromagnéticos , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Processamento de Imagem Assistida por Computador , Neuritos/ultraestrutura , Neurônios/fisiologia
8.
Vet Rec ; 168(19): 509, 2011 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-21546409

RESUMO

To evaluate the efficacy of halofuginone lactate (Halocur; Intervet) when used prophylactically against cryptosporidiosis in dairy calves, 513 Holstein heifer calves were randomly distributed between two experimental groups. Those in the treatment group (n=259) received 0.1 mg halofuginone base per kg bodyweight daily in a 10 ml solution, for the first seven days following birth, while those in the control group (n=254) received an equal volume of a placebo solution. Faecal samples were collected weekly from all calves until three weeks of age to test for Cryptosporidium oocysts and to assess the diarrhoeal status. Growth parameters of the calves were also recorded at approximately four months of age. Calves that received halofuginone were significantly less likely to shed Cryptosporidium oocysts during the course of the study than placebo-treated calves (odds ratio 0.6, 95 per cent confidence interval 0.4 to 0.9, P=0.009). Mean growth measurements of calves in the treated group were consistently higher than those of the control calves (hipometer-derived P=0.052, wither height P=0.097) and mortality was lower in the treated group (P=0.07). However, these differences were not statistically significant (P>0.05). No association was found between the prophylactic use of halofuginone and the incidence of calf diarrhoea.


Assuntos
Antiprotozoários/farmacologia , Doenças dos Bovinos/prevenção & controle , Criptosporidiose/veterinária , Cryptosporidium parvum/crescimento & desenvolvimento , Quinazolinonas/farmacologia , Animais , Animais Recém-Nascidos , Bovinos , Doenças dos Bovinos/epidemiologia , Criptosporidiose/epidemiologia , Criptosporidiose/prevenção & controle , Cryptosporidium parvum/efeitos dos fármacos , Cryptosporidium parvum/isolamento & purificação , Método Duplo-Cego , Fezes/parasitologia , Contagem de Ovos de Parasitas/veterinária , Distribuição Aleatória , Resultado do Tratamento
9.
Fitoterapia ; 81(8): 1113-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20627119

RESUMO

We investigated the in vitro effect of dibenzyl trisulfide (DTS), a secondary metabolite of Petiveria alliacea, on erythrocyte elasticity, relaxation time and membrane morphology. Blood samples from 8 volunteers with hemoglobin AA were exposed to 100, 200, 400, 800 and 1000 ng/ml of DTS respectively and the elasticity and relaxation time measured. There were statistically significant, dose-dependent increases in elasticity and relaxation times. The changes in membrane morphology observed also increased with increased concentration of DTS. This suggests that DTS interaction with membrane protein resulted in increased elasticity, relaxation time and deformation of the erythrocyte membrane.


Assuntos
Compostos de Benzil/química , Compostos de Benzil/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Phytolaccaceae/química , Phytolaccaceae/metabolismo , Sulfetos/química , Sulfetos/farmacologia , Feminino , Humanos , Masculino , Estrutura Molecular
11.
Ann R Coll Surg Engl ; 91(5): 361-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19409145

RESUMO

INTRODUCTION: Patients who have previously undergone meniscectomy are known to potentially suffer subsequent knee problems including degenerative changes. Meniscal transplantation has been proposed as a possible solution to these problems. This article aims to review the current literature to consolidate the evidence surrounding the use of human meniscal allograft transplantation. MATERIALS AND METHODS: Three databases (PubMed, Embase and Medline) were searched to find English language articles pertaining to meniscal allograft transplantation. Each article was critiqued by two authors using a structured appraisal tool, and stratified according to the level of evidence. RESULTS: No Level I or II studies were identified. Many studies had small study groups with limited follow-up and patient selection and description of patient factors varied greatly. This made comparing data difficult. There were also very few papers concentrating on isolated meniscal transplantation. Four types of graft are used--fresh, fresh-frozen, cryopreserved and freeze-dried (lyophilised) graft. Cryopreserved and fresh-frozen allografts are deemed most suitable. Most authors advocate the use of non-irradiated grafts from screened donors to reduce transmission of infection. Best results occur when using bony anchors to fix the graft, although this requires accurate graft positioning. Patients have an improved outcome if they have less severe degenerative changes within the knee prior to transplantation. CONCLUSIONS: No statistically significant studies looking at isolated meniscal transplantations have been found. The evidence suggests that meniscal allograft transplantation provides improvement of pain and function in the short and intermediate term. The effect on future joint degeneration is still unknown. The ideal patient group includes patients less than 40 years of age with knee pain, proven meniscal injury and a normally aligned, stable joint without severe degenerative changes.


Assuntos
Artralgia/cirurgia , Articulação do Joelho , Meniscos Tibiais/transplante , Transplante Homólogo/métodos , Adulto , Artroscopia/efeitos adversos , Humanos , Seleção de Pacientes , Índice de Gravidade de Doença , Resultado do Tratamento
13.
West Indian Med J ; 58(5): 407-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20441056

RESUMO

Studies conducted on the secondary metabolite (natural product), dibenzyl trisulphide (DTS), which was isolated from the sub-tropical shrub Petiveria alliacea (guinea hen weed, anamu) [Phytolaccaceae] have shown tremendous pharmaceutical promise as a drug prototype. This is now reflected in the development of the broad spectrum anti-cancer molecule, fluorapacin (bis(4-fluorobenzyl) trisulphide) which has an excellent safety profile. The mode of action elucidated for DTS is the mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases ERK 1 and ERK 2). The MAPKinase signal transduction biochemical pathways are important in the regulation of a wide range of cellular processes which are important in disease establishment. These processes include: cancer cell proliferation, nerve repair, memory enhancement, autoimmune diseases, which are linked to thymic cell involution and bone marrow functions, cerebrovascular and cardiovascular diseases. In addition to the MAPkinase signal transduction mode of action, DTS also prevents the denaturation of serum albumin which is a feature of nonsteroidal anti-inflammatory drugs, thus supporting the molecule's possible role in the treatment of inflammatory ageing diseases.


Assuntos
Compostos de Benzil/farmacologia , Desenho de Fármacos , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Fluorbenzenos/farmacologia , Phytolaccaceae , Transdução de Sinais/efeitos dos fármacos , Sulfetos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Extratos Vegetais/farmacologia
14.
West Indian Med J ; 58(2): 181-2, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21866606

RESUMO

The present article reports on the comparative cost of using the Bovine Serum Albumin as an assay for detecting natural products with anti-inflammatory activities relative to the use of animals. This is an addendum to the West Indian Medical Journal article; 2008; 57(4); 327-31.


Assuntos
Bioensaio , Soroalbumina Bovina/análise , Alternativas aos Testes com Animais/economia , Animais , Bioensaio/economia , Ratos , Ratos Sprague-Dawley
15.
J Dairy Sci ; 91(10): 3840-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18832206

RESUMO

Adequate passive transfer of maternal immunoglobulin is important for optimal health and performance in newborn dairy calves. From June to October 2003 and January to April 2004, blood samples were collected from 961 dairy calves 0 to 8 d of age on 11 farms in southwestern Ontario. This was followed by a second study conducted from May to October 2004, in which similar samples were taken from 422 calves up to 8 d of age on 119 dairy farms throughout southern Ontario. For each sample collected, serum refractometry was used to evaluate serum total protein (TP) as a measure of passive transfer of maternal immunity. During each study, producers were asked to provide information on calf management practices, including details of colostrum feeding. Data were analyzed to assess the levels of maternal immunity present in the calves, and to investigate whether these were associated with any calf management or colostrum feeding practices used on the farms. Serum TP readings ranged from 3.5 to 9.8 g/dL. Controlling for any effects of variation between farms, we found no statistically significant difference in serum TP levels, or risk of failure of passive transfer (FPT), between heifer and bull calves. The odds of FPT in calves on farms where more than 75% of cows were usually allowed to remain with their calves for more than 3 h after calving were significantly higher than the odds of FPT in calves on farms where dams and calves were separated within 3 h of the birth. Furthermore, an increased volume of colostrum given to calves within 6 h of birth was significantly associated with a reduced risk of FPT in calves. Information from this work provides valuable insight into the efficiency of passive transfer in newborn dairy calves in southern Ontario.


Assuntos
Bovinos/imunologia , Indústria de Laticínios/métodos , Imunização Passiva/veterinária , Animais , Proteínas Sanguíneas/análise , Métodos de Alimentação , Feminino , Modelos Logísticos , Masculino , Ontário , Inquéritos e Questionários
16.
Colorectal Dis ; 10(5): 460-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17953706

RESUMO

BACKGROUND: The use of a loop ileostomy is an effective method to protect pelvic anastomoses, although there is some debate as to the routine use of a stoma. A second operation is required to close the stoma, with potential complications. OBJECTIVE: The aim of this study was to assess prospectively the morbidity of closure of loop ileostomy. METHOD: All patients scheduled for loop ileostomy closure over a 12-month period were included. The patient demographics, operative technique, complications and length of stay were recorded prospectively. RESULTS: Fifty consecutive patients (28 males and 22 females) with a median age (interquartile range, IQR) of 56 (42-73) years underwent closure of loop ileostomy, at a median time (IQR) of 29 (18-48) weeks after formation. Twelve patients (24%) developed complications: six (12%) had intestinal obstruction of which one required a laparotomy, four (8%) had wound infections of which one required re-operation, one (2%) had an ileal anastomotic leak and subsequently died and one (2%) died from a myocardial infarction. The median length (IQR) of hospital stay was 8 (7-10) days. CONCLUSION: We have demonstrated that a quarter of patients develop complications after loop ileostomy closure. The majority of these are minor. Methods to reduce the number of complications, such as optimum time for closure and distal limb irrigation techniques, need to be studied.


Assuntos
Ileostomia , Adulto , Idoso , Feminino , Humanos , Ileostomia/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Reoperação , Resultado do Tratamento
17.
West Indian Med J ; 57(4): 327-31, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19566010

RESUMO

There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.


Assuntos
Anti-Inflamatórios/sangue , Preparações de Plantas/farmacologia , Desnaturação Proteica/efeitos dos fármacos , Soroalbumina Bovina/análise , Animais , Bioensaio , Bovinos , Descoberta de Drogas , Temperatura Alta/efeitos adversos , Doenças do Sistema Imunitário/tratamento farmacológico , Técnicas In Vitro , Programas de Rastreamento
18.
West Indian med. j ; 56(6): 487-490, Dec. 2007. tab
Artigo em Inglês | LILACS | ID: lil-507260

RESUMO

Mixed lymphocyte responses assays were conducted at 25.0 and 250.0 microg/mL of the crude ethanolic extract of Boehmeria jamaicensis Urb (coded as BJE) using peripheral lymphocytes obtained from individuals suffering from the common cold after four days of infection and from healthy individuals (without the common cold infection). At a concentration of 25 ug/mL, gamma interferon (IFN-gamma) was increased by 24.03 fold and interleukin 4 (IL-4) by 1.71 fold for the cells obtained from individuals with the common cold (Group A). The extract suppressed IFN-gamma by 8.3% while IL-4 was stimulated by 9.90 fold from peripheral lymphocytes obtained from healthy individuals (Group B). Gamma interferon was suppressed at 250 microg/mL while IL-4 was elevated by 1.86 fold for cells obtained from individuals suffering from the common cold (Group A). In conclusion, BJE could have implications for the treatment of the common cold.


Ensayos de reacci¨®n linfocitaria mixta fueron realizados a 25.0 y 250.0 ¦Ìg/mL de extracto etan¨®lico crudo de Boehmeria jamaicensis Urb (codificado como BJE), usando linfocitos perif¨¦ricos obtenidos de individuos con catarro com¨²n luego de cuatro d¨ªas de infecci¨®n, y de individuos sanos (sin la infecci¨®n del catarro com¨²n). Se hall¨® que el interfer¨®n-gamma (IFN-¦Ã) aument¨® en 24.03 veces, y la interleucina 4 (IL-4) en 1.71 veces para las c¨¦lulas obtenidas de individuos con catarro com¨²n, a 25¦Ìg/mL. El extracto inhibi¨® IFN-¦Ã en un 8.3 % en tanto que el IL-4 fue estimulado en 9.90 veces a partirde los linfocitos perif¨¦ricos obtenidos de individuos sanos. El gamma-interfer¨®n fue inhibido a 250 ¦Ìg/mL, mientras que la IL-4 se elev¨® en 1.86 veces para las c¨¦lulas obtenidas de individuos que sufren de catarro com¨²n.


Assuntos
Humanos , Boehmeria , Fitoterapia/métodos , Interferon gama/imunologia , /imunologia , Resfriado Comum/imunologia , Resfriado Comum/terapia , Sinusite/imunologia , Sinusite/terapia , Sinusite/microbiologia
19.
West Indian Med J ; 56(1): 5-10, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17621837

RESUMO

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24% and 50.83% anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.


Assuntos
Furanos/farmacologia , Myoporaceae , Neuroblastoma/tratamento farmacológico , Pentanonas/farmacologia , Fitoterapia , Sarcoma/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Humanos , Pentanonas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta
20.
West Indian Med J ; 56(1): 17-21, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17621839

RESUMO

The data compiled in the present review on dibenzyl trisulphide (DTS) isolated from Petiveria alliacea L (the guinea hen weed or anamu) revealed that the compound and its derivatives could be of tremendous pharmaceutical interest. The mode of action elucidated for DTS revealed that it is a mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases erk1 and erk 2) signal transduction molecule. Dibenzyl trisulphide caused hyper-phosphorylation of growth factor induced MAPKinases (erk 1 and erk 2) phosphorylation, a process critical for the improvement of long term memory, and is implicated in neuronal growth. Dibenzyl trisulphide and its derivatives exhibited potent anti-proliferation/cytotoxic activity on a wide range of cancer cell lines. The cytotoxic activity of DTS was increased by 70-1000 fold when bound to albumin in vitro. Dibenzyl trisulphide seems to have a cytokine switching mechanism in which it down regulates cytokines from the Type I helper cells (Th -1 cell) pathway which contained several pro-inflammatory cytokines and up-regulates those on the Type 2 helper cells (Th-2) pathway. The trisulphide up-regulates some reticuloendothelial system parameters eg granulocyte counts and increased thymic and Peyer's patches masses via cell proliferation processes which are known to be regulated via the MAPKinase signal transduction pathway. When the zygotes ofAsternia pectinifera (Starfish) were exposed to DTS at concentration of 10 mM, a dose lethal to all cancer cells tested, it was observed that the sensitive process of protein biosynthesis was not affected Similarly, the proliferation of the HOFA human fibroblast, a noncancerous cell line, was not severely affected by DTS at 8.9 microM over seven days, a concentration also lethal to most cancer cell lines tested The implications of the findings will be highlighted in the present review.


Assuntos
Compostos de Benzil/uso terapêutico , Fitoterapia , Extratos Vegetais , Sulfetos/uso terapêutico , Antígenos CD/fisiologia , Compostos de Benzil/farmacologia , Caderinas/fisiologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Sulfetos/farmacologia , Regulação para Cima/fisiologia
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