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1.
Animal ; 15(8): 100304, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34245954

RESUMO

Reduction in greenhouse gas emission from beef production is essential to the survival of the beef industry from environmental and social-economic perspectives. There are different systems available to measure methane from animals, but they are expensive, not easily accessible, and not suitable for large-scale methane measurements on the farm. Therefore exploring indicator traits, which are easy to measure, cost-effective, and suitable for large-scale measurement, are recommended. The objectives of this study were to examine the diversity of fecal methanogen profile among efficient and inefficient beef heifers on pasture and investigate methanogen profile as a possible proxy to predict methane emission in beef cattle consuming a forage diet. Forty pregnant (1st trimester) heifers previously classified for postweaning residual feed intake adjusted for off-test back fat (RFIfat; 20 high and 20 low) were included in this study. To determine individual pasture grazing intake, heifers were dosed with 1 kg of C32 labeled pellets once per day from Day 0 to Day 12, and fecal samples were collected twice daily from Day 8 to Day 15. Fecal samples from Days 8, 10, and 12 were analyzed for their methanogen profile. Animals were monitored individually for methane and carbon dioxide production using a GreenFeed Emissions Monitoring system. Total methanogen population and methanogenic community diversity of fecal samples were not different (P > 0.1) between low and high RFIfat groups, as measured by quantitative PCR and α- and ß-diversity indices. However, both groups had a different methanogen profile; the relative abundance of Methanobrevibacter wolinii and relatives were higher (P < 0.002), while that of Methanosphaera species ISO3-F5 was lower (P < 0.01) in low RFIfat cattle compared to the high RFIfat group. We also demonstrated that fecal methanogen profiles may be a useful proxy in predicting daily methane and carbon dioxide emissions with an adjusted R2 of 0.53 and 0.33, respectively, for low RFIfat heifers and 0.46 and 0.57, respectively, for the high RFIfat group.


Assuntos
Ração Animal , Ingestão de Alimentos , Ração Animal/análise , Animais , Bovinos , Dieta , Fezes , Feminino , Metano
2.
Can J Dent Hyg ; 53(2): 131, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33240351
3.
Br J Pharmacol ; 162(7): 1509-20, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21108630

RESUMO

BACKGROUND AND PURPOSE: Transient receptor potential canonical 5 (TRPC5) channels are widely expressed, including in the CNS, where they potentiate fear responses. They also contribute to other non-selective cation channels that are stimulated by G-protein-coupled receptor agonists and lipid and redox factors. Steroids are known to modulate fear and anxiety states, and we therefore investigated whether TRPC5 exhibited sensitivity to steroids. EXPERIMENTAL APPROACH: Human TRPC5 channels were conditionally expressed in HEK293 cells and studied using intracellular Ca2+ measurement, whole-cell voltage-clamp and excised patch techniques. For comparison, control experiments were performed with cells lacking TRPC5 channels or expressing another TRP channel, TRPM2. Native TRPC channel activity was recorded from vascular smooth muscle cells. KEY RESULTS: Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity within 1-2min. Dehydroepiandrosterone sulphate or 17ß-oestradiol had weak inhibitory effects. Pregnenolone, and allopregnanolone, a progesterone metabolite and stereo-isomer of pregnanolone, all had no effects. Progesterone was the most potent of the steroids, especially against TRPC5 channel activity evoked by sphingosine-1-phosphate. In outside-out patch recordings, bath-applied progesterone and dihydrotestosterone had strong and reversible effects, suggesting relatively direct mechanisms of action. Progesterone inhibited native TRPC5-containing channel activity, evoked by oxidized phospholipid. CONCLUSIONS AND IMPLICATIONS: Our data suggest that TRPC5 channels are susceptible to relatively direct and rapid stereo-selective steroid modulation, leading to channel inhibition. The study adds to growing appreciation of TRP channels as non-genomic steroid sensors.


Assuntos
Hormônios Esteroides Gonadais/farmacologia , Canais de Cátion TRPC/antagonistas & inibidores , Cálcio/metabolismo , Células Cultivadas , Di-Hidrotestosterona/farmacologia , Estradiol/farmacologia , Células HEK293 , Humanos , Lisofosfolipídeos/farmacologia , Miócitos de Músculo Liso/metabolismo , Técnicas de Patch-Clamp , Fosfolipídeos/metabolismo , Pregnenolona/farmacologia , Progesterona/farmacologia , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Canais de Cátion TRPC/química , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo
4.
Int J Dent Hyg ; 7(2): 136-43, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19416097

RESUMO

OBJECTIVES: Oral malodour is a common disorder predominantly caused by bacterial metabolism of food stuffs in the mouth. It is routinely diagnosed and monitored by either the subjective rating or the measurement of oral volatile sulphur compound (VSC) levels. Non-sulphur compounds are also believed to contribute significantly to the condition although there is currently no direct means to assess their levels. In this study, we utilized selective flow tube mass spectrometry (SIFT-MS) to measure, in real time, a range of sulphur and non-sulphur containing compounds in oral air to determine whether the technique can be used to objectively monitor oral malodour. METHODS: Oral malodour was assessed using organoleptic scores in subjects with and without a history of oral malodour (n = 18) by a trained rater, while the chemical composition of oral air was analysed by both VSC sensor and SIFT-MS. RESULTS: Total VSC levels were significantly correlated with levels of hydrogen sulphide and methylmercaptan measured by SIFT-MS, but not with organoleptic scores. In subjects with elevated organoleptic score, only levels of methylmercaptan were significantly elevated. In three subjects with elevated tongue organoleptic scores but normal total VSC levels, SIFT-MS suggested that one subject possessed high levels of oral acetone while another had high oral levels of acetic acid. CONCLUSIONS: Our data suggest that SIFT-MS can be used to assess a wide range of compounds in oral air in addition to VSC to provide a clearer picture of the chemical nature of malodour. This may assist in the diagnosis and monitoring of the condition.


Assuntos
Halitose/diagnóstico , Espectrometria de Massas/métodos , Boca/metabolismo , 1-Propanol/análise , Ácido Acético/análise , Acetona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Amônia/análise , Feminino , Halitose/metabolismo , Humanos , Sulfeto de Hidrogênio/análise , Masculino , Espectrometria de Massas/instrumentação , Pessoa de Meia-Idade , Odorantes/análise , Olfato , Compostos de Sulfidrila/análise , Compostos de Enxofre/análise , Língua/metabolismo , Compostos Orgânicos Voláteis/análise , Adulto Jovem
5.
Equine Vet J ; 40(4): 373-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18672437

RESUMO

REASONS FOR PERFORMING STUDY: Based on clinical observation, it is hypothesised that horses with duodenitis-proximal jejunitis (DPJ) that are treated surgically have a shorter duration, smaller volume, and slower rate of nasogastric reflux (NGR) compared to horses treated medically, are more likely to develop diarrhoea than medically managed cases, and have a higher incisional infection rate than a sample population of horses undergoing abdominal exploration for gastrointestinal disease other than DPJ. OBJECTIVES: To compare: 1) duration, volume and rate of NGR and the percentage of horses with diarrhoea between medically and surgically treated DPJ cases; and 2) incisional infection rate in horses with DPJ undergoing abdominal exploration to a sample population of horses undergoing abdominal exploration for gastrointestinal disease other than DPJ. METHODS: Medical records of cases with DPJ diagnosed 1995-2006 were reviewed. Information obtained included subject details, presenting clinical findings, treatment category (medical/surgical), complications (diarrhoea, incisional infection), and outcome (survival/nonsurvival). Data were analysed using a Chi-squared test and a mixed model analysis of variance. Level of significance was P<0.05. RESULTS: Compared to medical cases, surgical cases had significantly decreased survival, a longer duration and larger total volume of NGR, and were more likely to develop diarrhoea. The incisional infection rate for horses with DPJ undergoing abdominal exploration was 16% compared to 7% for the sample population of horses. CONCLUSIONS: Surgical treatment of horses with DPJ did not lead to resolution of NGR faster than medical treatment. Surgical cases were more likely to develop diarrhoea and did not have a significantly higher incisional infection rate than the sample population.


Assuntos
Duodenite/veterinária , Doenças dos Cavalos/mortalidade , Doenças do Jejuno/veterinária , Complicações Pós-Operatórias/veterinária , Análise de Variância , Animais , Distribuição de Qui-Quadrado , Diarreia/epidemiologia , Diarreia/mortalidade , Diarreia/veterinária , Duodenite/tratamento farmacológico , Duodenite/mortalidade , Duodenite/cirurgia , Feminino , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/mortalidade , Refluxo Gastroesofágico/veterinária , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/cirurgia , Cavalos , Doenças do Jejuno/tratamento farmacológico , Doenças do Jejuno/mortalidade , Doenças do Jejuno/cirurgia , Masculino , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/mortalidade , Infecção da Ferida Cirúrgica/veterinária , Análise de Sobrevida , Resultado do Tratamento
6.
Inj Prev ; 13(6): 422-5, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18056321

RESUMO

The accuracy of external cause of injury codes (E codes) for work-related and non-work-related injuries in Massachusetts emergency department data were evaluated. Medical records were reviewed and coded by a nosologist with expertise in E coding for a stratified random sample of 1000 probable work-related (PWR) and 250 probable non-work-related (PNWR) cases. Cause of injury E codes were present for 98% of reviewed cases and accurate for 65% of PWR cases and 57% of PNWR cases. Place of occurrence E codes were present in less than 30% of cases. Broad cause of injury categories were accurate for about 85% of cases. Non-specific categories (not elsewhere classified, not specified) accounted for 34% of broad category misclassifications. Among specified causes, machinery injuries were misclassified most often (39/60, 65%), predominantly as cut/pierce or struck by/against. E codes reliably identify the broad mechanism of injury, but inaccuracies and incompleteness suggest areas for training of hospital admissions staff, providers, and coders.


Assuntos
Serviço Hospitalar de Emergência/normas , Controle de Formulários e Registros/normas , Classificação Internacional de Doenças/normas , Sistemas Computadorizados de Registros Médicos/normas , Ferimentos e Lesões/etiologia , Humanos , Massachusetts , Ferimentos e Lesões/classificação
7.
Mult Scler ; 10(2): 219-30, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15124770

RESUMO

The aim of this phenomenological study was to gain an understanding of the experiences of a group of caregivers of people with multiple sclerosis (MS). Sixteen caregivers from Northern Ireland and the Republic of Ireland participated in focus group interviews. The theme of support, either sought or received, emerged as a major aspect of the experiences described. Caregivers' feelings about, and experiences of, support appeared to change over time. Four common phases that caregivers experienced in relation to support were identified as: 'rejecting', 'resisting, 'seeking' and 'accepting' support. This paper will present and discuss these four phases. The study findings highlight the complexity of issues surrounding a caregiver's decision to seek and accept support. It is hoped that the phases identified within this study are useful in depicting how caregivers of people with MS may progress through stages in their desire for, and acceptance of support. Findings from this study are useful to healthcare professionals who work with people with MS and their caregivers by increasing awareness that a caregiver's attitude toward and acceptance of support changes over time.


Assuntos
Cuidadores/psicologia , Esclerose Múltipla/psicologia , Esclerose Múltipla/reabilitação , Apoio Social , Adolescente , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Participação do Paciente
8.
Clin Rehabil ; 17(3): 234-48, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12735530

RESUMO

PRIMARY OBJECTIVE: To appraise recent studies regarding the needs and experiences of caregivers of individuals with multiple sclerosis (MS). DESIGN: The following computerized databases were searched: CINAHL, BIDS IBSS, ASSIA, MEDLINE, PSYCHINFO, British Nursing Index, ISI Web of Science, Zetoc, AMED (1990-April 2002). The computer-based search was supplemented by manual searches of the reference lists of all retrieved studies and review articles. Inclusion and exclusion criteria were formulated. RESULTS: Twenty-four studies from across the world that met the inclusion criteria were reviewed. The majority of studies were descriptive in nature. The studies covered a variety of topics, including how carers assist people with MS, the effect of providing care on a carer's physical and psychological well-being, social life, financial situation and overall quality of life, and how carers cope with the stresses of providing care. CONCLUSIONS: Providing care for a person with MS has a major impact on all areas of the caregiver's life. Perceived social support has been shown to have a beneficial impact on the caregiver. Limitations in design and variation in methodology of studies limits the generalizability of findings. There is a need for further research, in particular the development of reliable and valid disease-specific caregiver assessment instruments.


Assuntos
Cuidadores/psicologia , Esclerose Múltipla/classificação , Apoio Social , Humanos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
9.
Int J Dent Hyg ; 1(4): 213-7, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16451502

RESUMO

In this retrospective qualitative study, the researcher reviewed 55 client records of The Breath Odour Clinic. The purpose was to determine if individuals attended a clinic specialised in treating oral malodour for medical or social reasons. The study focused on the psychosocial and breath odour history. Clients had agreed to the use of information for research purposes. Society uses odour as a means to define and interact with the world. The olfactory, smelling experience is intimate, emotionally charged and connects us with the world. It follows that the smell from mouth breath odour can connect or disconnect a person from their social environment and intimate relationships. How one experiences one's own body is very personal and private but also very public. Breath odour is public as it occurs within a social and cultural context and personal as it affects one's body image and self-confidence. Body image, self-image and social relations mesh, interact and impact upon each other. Breath odour is a dynamic and interactive aspect of the self-image. In addition, breath odour may be value-coded as 'bad'. In 75% of the cases reviewed, decreased self-confidence and insecurity in social and intimate relations led clients to seek treatment at the specialised breath odour clinic. Their doctor, dental hygienist or dentist had treated medical and oral conditions but not resolved their breath odour problem. When a person perceives a constant bad breath problem, she/he uses defence techniques, and may avoid social situations and social relations. This affects a person's well-being.


Assuntos
Halitose/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Saúde , Imagem Corporal , Criança , Mecanismos de Defesa , Feminino , Halitose/terapia , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Autoimagem , Meio Social
10.
Int J Dent Hyg ; 1(1): 43-8, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16451545

RESUMO

Recently the discourse in Canada relating to dental hygiene practice has changed. While dentistry still exercises controlling power over the public's oral cavity, dental hygienists have made inroads through legislative changes. A description of Canadian dental hygiene practice is provided to set the stage for a discussion about current discourse in the dental hygiene profession. Although power is often perceived as a shifting changing set of relations, these can be frozen in abstraction. It is rather like taking a photo of a single moment or event in an ongoing activity. This moment provides a starting point, an event that can be analysed. Four such events are evident in Canadian dental hygiene practice; they include, education, recognition of dental hygienists as primary care providers, the culture of dental hygiene and self-regulation. While all the events are important, self-regulation is critical to the viability and development of the profession. It is the central event that provides the backdrop for effecting change. With self-regulation comes responsibility and accountability for professional actions. It also provides possibilities for changing the discourse in oral care. As oral health care discourse is transformed through legislation and public awareness, the public will, hopefully, be able to directly access dental hygiene services, and dental hygienists themselves might increasingly recognise their importance as contributors in the health care system.


Assuntos
Assistência Odontológica/legislação & jurisprudência , Higienistas Dentários , Canadá , Assistência Odontológica/história , Higienistas Dentários/educação , Higienistas Dentários/legislação & jurisprudência , História do Século XX , Humanos , Autonomia Profissional , Prática Profissional/legislação & jurisprudência , Papel Profissional/história , Sociedades Odontológicas
11.
Am J Hematol ; 59(2): 115-20, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9766795

RESUMO

The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.


Assuntos
Albinismo Oculocutâneo/sangue , Plaquetas/metabolismo , Fator de von Willebrand/fisiologia , Trifosfato de Adenosina/metabolismo , Adolescente , Adulto , Albinismo Oculocutâneo/fisiopatologia , Tempo de Sangramento , Plaquetas/química , Criança , Pré-Escolar , Fator VIII/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/fisiologia , Fator Plaquetário 4/análise , Deficiência do Pool Plaquetário/sangue , Deficiência do Pool Plaquetário/fisiopatologia , Porto Rico/etnologia , beta-Tromboglobulina/análise , Fator de von Willebrand/análise
14.
J Lab Clin Med ; 128(5): 492-5, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8900292

RESUMO

The platelet glycoprotein Ib(alpha) (GPIb(alpha)) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb(alpha) that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation induced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptides were synthesized from the peptide sequence F216-T240. Several of the peptides derived from the sequence W219-V227 of GPIb(alpha) inhibited platelet aggregation, which was primarily dependent on the presence of the amino acid sequence A224-N226 (AEN). These data suggest that a region within the GPIb(alpha) chain modulates the platelet aggregation induced by alpha-thrombin. These GPIb(alpha) peptides did not interfere with platelet aggregation induced by other agonists--for example, collagen, ristocetin, calcium ionophore, or botrocetin--which indicates that these GPIb(alpha) peptide-platelet interaction(s) are specific. Our studies provide another potential mechanism for modulating platelet activation and aggregation via synthetic and natural peptides.


Assuntos
Fragmentos de Peptídeos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIb-IX de Plaquetas/farmacologia , Sequência de Aminoácidos , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/química , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Receptores de Trombina/química , Receptores de Trombina/genética , Relação Estrutura-Atividade , Trombina/antagonistas & inibidores , Trombina/farmacologia
15.
J Hand Surg Am ; 21(2): 202-9, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8683047

RESUMO

This article provides a qualitative and quantitative outcomes assessment of a consecutive series of 27 patients (30 thumbs) with basal joint arthritis of the thumb undergoing ligament reconstruction and tendon interposition arthroplasty. Outcome analysis revealed that 24 (89%) patients were satisfied with the relief of pain provided by the arthroplasty and 23 (87%) would undergo surgery again. Eighteen (67%) thumbs were noted to have improvement in the ability to perform activities of daily living. Significant improvements were noted in web space measurements and in grip and pinch strength determination. X-ray film assessment using the trapezial space ratio averaged 0.33 +/- 0.08 in preoperative x-ray films of thumbs with stage III and IV degenerative arthritis and 0.23 +/- 0.07 in thumbs following basal joint arthroplasty. This represents a total decrease of 51% in the trapezial space ratio following arthroplasty compared to the normal values obtained in previous studies and 33% compared to the preoperative values obtained in this study. Outcomes assessment at a mean of 42 months after surgery showed that there was no significant correlation between maintenance of trapezial height and both objective and subjective clinical outcomes. Although ligament reconstruction consistently failed to restore trapezial height, primary and secondary clinical outcomes following basal joint arthritis were almost uniformly satisfactory.


Assuntos
Artroplastia/métodos , Ossos do Carpo/cirurgia , Ligamentos Articulares/cirurgia , Osteoartrite/cirurgia , Transferência Tendinosa/métodos , Atividades Cotidianas/classificação , Adulto , Idoso , Ossos do Carpo/diagnóstico por imagem , Feminino , Força da Mão/fisiologia , Humanos , Ligamentos Articulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Medição da Dor , Satisfação do Paciente , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Resultado do Tratamento
16.
Am J Hematol ; 51(2): 158-63, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8579058

RESUMO

DDAVP is effective treatment in most types of von Willebrand's disease; however, in type 2B von Willebrand's disease the use of DDAVP has been contraindicated due to DDAVP-induced thrombocytopenia. Several reports have confirmed the thrombocytopenic effects of DDAVP and the presence of circulating platelet aggregates in type 2B von Willebrand's disease. We have infused three type 2B patients with DDAVP. The three patients had different mutations of their vWf. All three patients had a missense mutation which resulted in a single amino acid substitution in the disulfide loop of the A1 domain. Administration of 20 micrograms of DDAVP resulted in significant elevations of factor VIII, vWf antigen, and ristocetin cofactor levels. In contrast to other studies, DDAVP did not induce or enhance thrombocytopenia in these three patients. When blood was obtained by fingerstick and diluted into sodium oxalate (Unopette) or EDTA (Microvette), the platelet counts did not change over 4 hr. In contrast, blood collected directly into evacuated tubes containing sodium citrate, lithium heparin, or EDTA consistently demonstrated varying degrees of thrombocytopenia and platelet clumping. We also observed a shortening of the pre-infusion bleeding time over the 4 hr period. All three patients have been studied twice and each has shown consistent results. DDAVP appears to be a useful form of treatment in type 2B vWd.


Assuntos
Desamino Arginina Vasopressina/administração & dosagem , Fármacos Renais/administração & dosagem , Doenças de von Willebrand/tratamento farmacológico , Adulto , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Trombocitopenia/tratamento farmacológico , Doenças de von Willebrand/sangue
17.
Thromb Res ; 81(1): 113-9, 1996 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8747526

RESUMO

We have previously described a monomeric rvWf fragment, Leu504-Lys728 that contains one disulfide bond linking Cys509-Cys695. This fragment, VCL, has previously been shown to inhibit vWf-ristocetin, asialo-vWf, and botrocetin-induced vWf binding and aggregation of platelets. VCL inhibited 50% of vWf binding to heparin, but it did not inhibit vWf binding to type I collagen. At a high shear force (2600-1 sec), VCL inhibited platelet adhesion to the subendothelial surface of human umbilical arteries. The maximum inhibition of platelet adhesion was 83 +/- 4% at a VCL concentration of 7.6 mumol/L. Various monoclonal anti-Very Late Activation antigens (VLA) antibodies were added to the VCL and tested for their ability to enhance the inhibition of platelet adhesion at high shear forces. Of all of the VLA antibodies tested, only the anti-VLA-2 antibody (176D7) inhibited platelet aggregation in the absence of VCL and enhanced the inhibition of platelet adhesion in the presence of VCL. The VLA-2 antibody and VCL together inhibited 96 +/- 4% of platelet adhesion at high shear forces.


Assuntos
Hemorreologia , Integrina beta1/fisiologia , Integrinas/fisiologia , Fragmentos de Peptídeos/farmacologia , Adesividade Plaquetária , Glicoproteínas da Membrana de Plaquetas/fisiologia , Receptores de Superfície Celular/fisiologia , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Colágeno/metabolismo , Heparina/metabolismo , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/farmacologia , Imunoglobulina G/imunologia , Imunoglobulina G/farmacologia , Integrinas/imunologia , Músculo Liso Vascular/metabolismo , Adesividade Plaquetária/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Receptores de Colágeno , Proteínas Recombinantes/farmacologia , Artérias Umbilicais , Fator de von Willebrand/fisiologia
18.
Br J Haematol ; 91(3): 697-702, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8555078

RESUMO

One of the major causes of morbidity and mortality in paroxysmal nocturnal haemoglobinuria (PNH) is venous thrombosis. We have studied fibrinolysis, coagulation and platelets in 11 patients with PNH in an attempt to identify the possible mechanism(s) of thrombosis in PNH. In this study we did not identify any fibrinolytic defects, evidence of coagulation activation, nor reduction in coagulation inhibitors. In contrast, in this cohort of 11 PNH patients we have identified varying degrees of platelet activation as defined by the surface expression of activation-dependent proteins and the binding of adhesive proteins to the platelet surface. The thrombotic events in PNH usually occur in the venous system. Our studies and previous experimental studies suggest that anti-platelet therapy may be efficacious in reducing the incidence and severity of venous thrombosis in PNH.


Assuntos
Coagulação Sanguínea/fisiologia , Hemoglobinúria Paroxística/fisiopatologia , Ativação Plaquetária/fisiologia , Adolescente , Adulto , Idoso , Feminino , Citometria de Fluxo , Hemoglobinúria Paroxística/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Proteína C/metabolismo , Proteína S/metabolismo , Trombose/etiologia , Trombose/fisiopatologia
19.
Br J Haematol ; 88(3): 582-91, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7819071

RESUMO

Platelet von Willebrand factor (vWf) was purified from human platelet concentrates. The multimeric structure of the purified platelet vWf was similar to that observed in the initial platelet lysate, and, like the platelet lysate, the purified platelet vWf contained higher molecular weight multimers than plasma vWf. The apparent molecular weight of the reduced platelet vWf subunit was similar to the plasma vWf subunit. The N-terminal amino acid of the purified platelet and plasma vWf was blocked. In concentration dependent binding to botrocetin- or ristocetin-stimulated platelets, 125I-plasma vWf bound with a higher affinity than platelet. The ristocetin cofactor activity per mg of purified plasma vWf was 5-fold greater than the platelet vWf activity. Platelet and plasma vWf bound to collagen with similar affinities; however, platelet vWf bound to thrombin-stimulated platelets and to heparin with a higher affinity than plasma vWf. The differences in the binding affinity(s) of plasma and platelet vWf to platelet GPIb and GPIIb/IIIa and extracellular matrix proteins may reflect different roles for plasma and platelet vWf in the initial stages of haemostasis and thrombosis.


Assuntos
Plaquetas/química , Fator de von Willebrand/isolamento & purificação , Sequência de Aminoácidos , Anticorpos Monoclonais/metabolismo , Plaquetas/metabolismo , Eletroforese em Gel de Ágar , Ensaio de Imunoadsorção Enzimática , Humanos , Dados de Sequência Molecular , Peso Molecular , Plasma , Glicoproteínas da Membrana de Plaquetas/metabolismo , Ristocetina/metabolismo , Trombina/metabolismo , Fator de von Willebrand/química , Fator de von Willebrand/metabolismo
20.
Proc Natl Acad Sci U S A ; 91(14): 6334-8, 1994 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-8022782

RESUMO

alpha-Thrombin binding to and activation of platelets are of major importance in the initiation of physiologic thrombi and in the genesis of arterial thrombus formation. We have studied the site(s) and affinity of thrombin binding to human platelets. Our studies of the peptide inhibition of thrombin binding indicate that the glycoprotein Ib alpha binding site is of high affinity, Kd approximately 10(-10) M, while the seven-transmembrane-domain site is a moderate-affinity thrombin binding site, Kd approximately 10(-8) M. Further studies to modulate the high- or moderate-affinity thrombin binding can be directed to a specific class of sites. This would allow partial or total inhibition of specific thrombin-platelet interaction(s) in different clinical settings.


Assuntos
Plaquetas/fisiologia , Fragmentos de Peptídeos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/química , Glicoproteínas da Membrana de Plaquetas/metabolismo , Trombina/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Plaquetas/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Cinética , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Mapeamento de Peptídeos , Peptídeos , Relação Estrutura-Atividade , Trombina/farmacologia , Venenos de Vespas/farmacologia
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