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1.
BMC Vet Res ; 13(1): 334, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29141627

RESUMO

BACKGROUND: Platelet transfusion therapy poses many challenges in veterinary clinical practice. Lack of readily available blood donors, short shelf-life, and inability to administer a sufficient number of platelets to meet a dog's transfusion need are the major difficulties encountered. Platelet additive solutions are already in use at American and European human blood banks, showing to be a realistic alternative. This study compares the in vitro platelet function in plasma, Composol, or SSP+ during storage for 13 days. Platelet rich plasma-platelet concentrate with 35% plasma and 65% platelet additive solutions (Composol or SSP+) and a control group (100% plasma) were prepared. Swirling, platelet count, blood gases, metabolic variables, platelet activation markers, and apoptosis markers were analyzed on days 1, 5, 9 and 13. RESULTS: Swirling was well preserved and pH was acceptable (> 6.2) during storage for all platelet additive solutions units until day 9. SSP + units showed more stable pH and metabolic variables until day 13. Platelets in plasma showed higher glucose consumption than in Composol or in SSP+. The platelet additive solutions units showed better platelet metabolism maintenance, reduced glucose consumption and lactate production. The apoptotic markers were still low for 9 days in platelet concentrates with platelet additive solutions, suggesting the possibility to extend the shelf life with the use of SSP+ or Composol. CONCLUSIONS: Our findings suggest that the uses of Composol and SSP+ in canine platelet concentrates are potential alternatives in veterinary blood banks.


Assuntos
Plaquetas , Preservação de Sangue/veterinária , Meios de Cultura , Cães/sangue , Animais , Plaquetas/fisiologia , Meios de Cultura/química , Estudos de Viabilidade , Contagem de Plaquetas , Soluções/química
2.
J Clin Pharmacol ; 57(11): 1432-1443, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28703316

RESUMO

Ertugliflozin is a highly selective and potent inhibitor of the sodium-glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The glycemic efficacy of sodium-glucose cotransporter 2 inhibitors such as ertugliflozin depends on glucose filtration through the kidney. This phase 1, open-label study evaluated the effect of renal impairment on the pharmacokinetics, pharmacodynamics, and tolerability of ertugliflozin (15 mg) in type 2 diabetes mellitus and healthy subjects with normal renal function (estimated glomerular filtration rate not normalized for body surface area ≥90 mL/min) and type 2 diabetes mellitus subjects with mild (60-89 mL/min), moderate (30-59 mL/min), or severe (<30 mL/min) renal impairment (n = 36). Blood and urine samples were collected predose and over 96 hours postdose for pharmacokinetic evaluation and measurement of urinary glucose excretion over 24 hours. Log-linear regression analyses indicated predicted mean area under the concentration-time curve values for mild, moderate, and severe renal function groups that were ≤70% higher relative to subjects with normal renal function. Generally consistent results were obtained with categorical analysis based on analysis of variance. The increase in ertugliflozin exposure in subjects with renal impairment is not expected to be clinically meaningful. Regression analysis of change from baseline in urinary glucose excretion over 24 hours vs estimated glomerular filtration rate showed a decrease in urinary glucose excretion with declining renal function. A single 15-mg dose of ertugliflozin was well tolerated in all groups.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insuficiência Renal/metabolismo , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Glucose/metabolismo , Glucosídeos/metabolismo , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Transportador 2 de Glucose-Sódio/metabolismo
3.
Development ; 143(7): 1087-98, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26893342

RESUMO

Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.


Assuntos
Fator 6 de Diferenciação de Crescimento/genética , Neurogênese/genética , Retina/embriologia , Tretinoína/metabolismo , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Ciclo Celular/genética , Proliferação de Células , Embrião não Mamífero/embriologia , Neurogênese/fisiologia , Transdução de Sinais/genética , Células-Tronco/citologia
5.
Arq. bras. med. vet. zootec ; 66(5): 1311-1316, Sep-Oct/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-729778

RESUMO

The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1), cancer-associated antigen 72-4 (CA 72-4) and carcinoembryonic antigen (CEA) in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16) and non-neoplastic (n=16) samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistical difference was found only for the CYFRA 21-1 marker. The levels were significantly higher for the neoplastic group. The lack of significance between groups for markers CA 72-4 and CEA can be explained by the presence of other diseases in the non-neoplastic group, causing elevated levels of these markers. This study concludes that CYFRA 21-1 performed well, showing good sensitivity, specificity and accuracy in the diagnosis of neoplastic effusions in dogs. However, further investigations are necessary in patients with malignancy as those with benign effusions...


Os níveis de marcadores tumorais em líquidos corporais podem ser usados para diagnóstico e prognóstico de pacientes. Este estudo objetiva investigar o desempenho dos marcadores tumorais fragmento de citoqueratina 19 (CYFRA 21-1), antígeno asociado ao câncer 72-4 (CA 72-4) e antígeno carcinoembrionário (CEA) em efusões caninas neoplásicas e não neoplásicas. Os marcadores tumorais foram mensurados em 32 amotras de efusões torácicas e abdominais de cães, 16 neoplásicas e 16 não neoplásicas. Foi encontrada diferença estatística somente para o marcador CYFRA 21-1, onde os níveis foram significativamente altos no grupo neoplásico. A falta de significância entre os grupos de marcadores CA 72-4 e CEA pode ser explicada pela presença de outras doenças no grupo não neoplásico, o que causou elevação dos níveis destes marcadores. Este estudo conclui que o marcador CYFRA 21-1 teve bom desempenho, pois mostrou boa sensibilidade, especificidade e acurácia no diagnóstico de efusões neoplásicas em cães. Entretanto, mais estudos são necessários tanto em pacientes portadores de efusões benignas quanto malignas...


Assuntos
Animais , Cães , Biomarcadores Tumorais/análise , Neoplasias/diagnóstico , Neoplasias/veterinária , Queratinas/administração & dosagem
6.
J Psychosoc Nurs Ment Health Serv ; 52(12): 24-8, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25207557

RESUMO

Experiential teaching strategies have the potential to more effectively help students with critical thinking than traditional lecture formats. Gaming is an experiential teaching-learning strategy that reinforces teamwork, interaction, and enjoyment and introduces the element of play. Two Bachelor of Science in Nursing students and a clinical instructor created a Jeopardy!(®)-style game to enhance understanding of psychopharmacology, foster student engagement in the learning process, and promote student enjoyment during clinical postconference. The current article evaluates the utility, relevance, and effectiveness of gaming using a Jeopardy!(®)-style format for the psychiatric clinical setting. Students identified the strengths of this learning activity as increased awareness of knowledge deficits, as well as the reinforcement of existing knowledge and the value of teamwork.


Assuntos
Pesquisa em Educação em Enfermagem/métodos , Jogos e Brinquedos , Aprendizagem Baseada em Problemas/métodos , Enfermagem Psiquiátrica/educação , Psicofarmacologia/educação , Estudantes de Enfermagem , Conscientização , Humanos
7.
J Dairy Sci ; 97(1): 543-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24210484

RESUMO

This study was performed to evaluate α-tocopherol and ß-carotene contents of pasture milk under ordinary Sicilian farming conditions. Fourteen dairy farms were allocated into 2 balanced groups on the basis of cultivated (CULT) or spontaneous (SPO) pasture type feeding. Bulk milk per farm was collected 4 times from February through April at 3-wk intervals. Pasture botanical and diet composition, diet nutritional quality, milk yield and composition were estimated each time. Pasture intake levels were calculated based on feed analyses, hay and concentrate amounts fed, and milk yield and chemical composition. According to pasture intake, the farms were split into low pasture intake (LPI; <29.5% of dry matter) and high pasture intake (HPI; >29.5% of dry matter) groups. Milk samples per farm were analyzed for α-tocopherol and ß-carotene contents by HPLC. The SPO group had higher levels of α-tocopherol and ß-carotene in milk (0.7 and 0.3 mg/L, respectively) and milk fat (19.0 and 7.5 mg/kg fat, respectively) compared with the CULT group in milk (0.5 and 0.2 mg/L, respectively) and milk fat (14.6 and 4.9 mg/kg, respectively). High pasture intake compared with LPI increased α-tocopherol in milk fat (18.0 and 16.0 mg/kg of fat, respectively). However, only in the SPO (not in CULT), HPI compared with LPI increased milk α-tocopherol (0.8 vs. 0.6 mg/L, respectively), milk ß-carotene (0.3 vs. 0.2 mg/L, respectively), and milk fat ß-carotene (8.4 vs. 6.6 mg/kg, respectively). Results may be related to the different botanical composition of the respective pasture types and pasture intake. Spontaneous pasture compared with CULT contained a higher mass proportion of Asteraceae, Fabaceae, Cruciferae, Euphorbiaceae, and Malvaceae plants. Milk and milk fat α-tocopherol levels were higher on test-days (TD)-1, TD-2, and TD-4 compared with TD-3. For HPI farms, milk fat ß-carotene content was higher on the first 2 TD compared with the last 2 TD. These differences could be related to plant biological stage. On Sicilian dairy farms, the highest milk α-tocopherol and ß-carotene contents may be obtained feeding high levels of SPO pasture in the spring.


Assuntos
Bovinos/fisiologia , Leite/química , alfa-Tocoferol/análise , beta Caroteno/análise , Ração Animal , Criação de Animais Domésticos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino , Sicília , beta Caroteno/metabolismo
8.
Water Res ; 47(2): 781-90, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23206500

RESUMO

Gas exchange can be a key component of the dissolved oxygen (DO) mass balance in aquatic ecosystems. Quantification of gas transfer rates is essential for the estimation of DO production and consumption rates, and determination of assimilation capacities of systems receiving organic inputs. Currently, the accurate determination of gas transfer rate is a topic of debate in DO modeling, and there are a wide variety of approaches that have been proposed in the literature. The current study investigates the use of repeated measures of stable isotopes of O2 and DO and a dynamic dual mass-balance model to quantify gas transfer coefficients (k) in the Grand River, Ontario, Canada. Measurements were conducted over a longitudinal gradient that reflected watershed changes from agricultural to urban. Values of k in the Grand River ranged from 3.6 to 8.6 day⁻¹, over discharges ranging from 5.6 to 22.4 m³ s⁻¹, with one high-flow event of 73.1 m³ s⁻¹. The k values were relatively constant over the range of discharge conditions studied. The range in discharge observed in this study is generally representative of non-storm and summer low-flow events; a greater range in k might be observed under a wider range of hydrologic conditions. Overall, k values obtained with the dual model for the Grand River were found to be lower than predicted by the traditional approaches evaluated, highlighting the importance of determining site-specific values of k. The dual mass balance approach provides a more constrained estimate of k than using DO only, and is applicable to large rivers where other approaches would be difficult to use. The addition of an isotopic mass balance provides for a corroboration of the input parameter estimates between the two balances. Constraining the range of potential input values allows for a direct estimate of k in large, productive systems where other k-estimation approaches may be uncertain or logistically infeasible.


Assuntos
Monitoramento Ambiental/métodos , Água Doce/química , Limnologia/métodos , Modelos Químicos , Oxigênio/análise , Qualidade da Água , Recursos Hídricos , Calibragem , Difusão , Ontário , Oxigênio/química , Isótopos de Oxigênio , Rios , Solubilidade , Análise Espaço-Temporal , Urbanização , Poluição Química da Água/efeitos adversos
9.
J Dairy Sci ; 95(1): 460-70, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22192226

RESUMO

Composition and physical properties of cheeses are influenced by temperature, salt, and calcium concentration of brine. This work aimed to examine conditions of brine under which the cheese matrix contracts or expands in absence of restrictions imposed by surface rind development during overnight block formation. Three experimental 4-kg blocks of Ragusano cheese were produced at 3 different stretching temperatures (70, 80, and 90°C) and cut into pieces weighing approximately 40 to 50 g. One piece from each was chemically analyzed at time 0. All other pieces were measured for weight and volume and placed in plastic bags containing 300 mL of different brine solutions (2% NaCl with 0.1% Ca; 10% NaCl with 0, 0.1, 0.2, or 0.4% Ca; 18% NaCl with 0.1% Ca; and 26% NaCl with 0.1% Ca) at 3 different temperatures (4, 12, and 20°C). After 24h of brining, the cheeses were analyzed for weight, volume, chemical, and microstructural changes. Salt concentration in brine significantly influenced composition, weight, and volume of the cheeses after brining. Salt concentration was inversely related to cheese volume and weight. Changes in weight caused by altering the brining temperature were sufficient to reach statistical significance, and statistically significant volume changes were induced by brining temperature and its interaction with salt content. The highest volume increase (30%) occurred in the cheese stored in the 2% NaCl brine at the coldest temperature, whereas the greatest volume decrease was recorded in cheeses brined in the 26% NaCl brine. Composition was not affected by brining temperature. Calcium concentration did influence weight, volume, and composition, except on a fat-on-dry-basis. When cheeses were brined without added calcium, cheese volume and weight increased at all temperatures. At high calcium levels (0.4%), syneresis occurred and volume decreased, especially at 20°C (-16.5%). Microstructural investigation with porosity measurement confirmed weight and volume changes.


Assuntos
Queijo/normas , Tecnologia de Alimentos/métodos , Cálcio/análise , Queijo/análise , Proteínas/análise , Sais/análise , Sais/química , Cloreto de Sódio/análise , Temperatura
10.
Exp Clin Endocrinol Diabetes ; 119(7): 401-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21472661

RESUMO

The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A (1C) (HbA (1c)) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA (1c) were -0.31% (-0.70 to 0.08), -0.74% (-1.12 to -0.36), -0.70% (-1.02 to -0.38), and -0.75% (-1.07 to -0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (-12.8% [-22.9 to -2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA (1c) in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4 , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Inibidores de Proteases/administração & dosagem , Pirimidinas/administração & dosagem , Pirrolidinas/administração & dosagem , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Inibidores de Proteases/efeitos adversos , Pirimidinas/efeitos adversos , Pirrolidinas/efeitos adversos
11.
Diabet Med ; 28(4): 464-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21392067

RESUMO

AIMS: PF-734200 is a potent and selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor. This study assessed the efficacy and safety of PF-734200 at dose rates of 20 and 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy. METHODS: This was a placebo-controlled, double-blind, randomized, multicentre, 12 week study. Subjects with Type 2 diabetes mellitus were eligible if screening glycosylated haemoglobin (HbA(1c) ) was 7-11% (53.0-96.7 mmol/mol) and they had been receiving metformin monotherapy for ≥2 months. Subjects receiving metformin and an insulin secretagogue or metformin and thiazolidinedione needed to have a screening HbA(1c) of 6.5-9.5% (47.5-80.3 mmol/mol), measured prior to discontinuing the insulin secretagogue or thiazolidinedione. The primary end-point of the study was a change from baseline to week 12 in HbA(1c) levels. RESULTS: Baseline characteristics for 289 subjects randomized to PF-734200 or placebo groups were similar (mean age 56.5 years, mean body mass index 32.2 kg/m(2) and mean HbA(1c) 8.2%, 66.1 mmol/mol). In the predefined per protocol data set, least-squares mean HbA(1c) at week 12 was reduced by 0.79 (8.6 mmol/mol 95% confidence interval -1.10 to -0.49, -12.0 to -5.4 mmol/mol) and 0.92% (10.1 mmol/mol; -1.23 to -0.61, -13.4 to -6.7 mmol/mol) in the 20 and 30 mg groups, respectively, compared with placebo. Differences from placebo were statistically significant (P<0.0001), but the differences between the 20 and 30 mg groups were not. The intent-to-treat analysis yielded similar findings. CONCLUSIONS: The HbA(1c) was significantly and meaningfully reduced by both doses of PF-734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long-term controlled studies.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Dipeptidil Peptidase IV/farmacologia , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Pirrolidinas/administração & dosagem , Pirrolidinas/farmacologia , Resultado do Tratamento , Adulto Jovem
12.
Xenobiotica ; 39(10): 766-81, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19622022

RESUMO

5-{2-[4-(3,4-Difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid (1) is a novel, potent, and selective agonist of the peroxisome proliferator-activated receptor alpha (PPAR-alpha). In preclinical species, compound 1 demonstrated generally favourable pharmacokinetic properties. Systemic plasma clearance (CLp) after intravenous administration was low in Sprague-Dawley rats (3.2 +/- 1.4 ml min(-1) kg(-1)) and cynomolgus monkeys (6.1 +/- 1.6 ml min(-1) kg(-1)) resulting in plasma half-lives of 7.1 +/- 0.7 h and 9.4 +/- 0.8 h, respectively. Moderate bioavailability in rats (64%) and monkeys (55%) was observed after oral dosing. In rats, oral pharmacokinetics were dose-dependent over the dose range examined (10 and 50 mg kg(-1)). In vitro metabolism studies on 1 in cryopreserved rat, monkey, and human hepatocytes revealed that 1 was metabolized via oxidation and phase II glucuronidation pathways. In rats, a percentage of the dose (approximately 19%) was eliminated via biliary excretion in the unchanged form. Studies using recombinant human CYP isozymes established that the rate-limiting step in the oxidative metabolism of 1 to the major primary alcohol metabolite M1 was catalysed by CYP3A4. Compound 1 was greater than 99% bound to plasma proteins in rat, monkey, mouse, and human. No competitive inhibition of the five major cytochrome P450 enzymes, namely CYP1A2, P4502C9, P4502C19, P4502D6 and P4503A4 (IC50's > 30 microM) was discerned with 1. Because of insignificant turnover of 1 in human liver microsomes and hepatocytes, human clearance was predicted using rat single-species allometric scaling from in vivo data. The steady-state volume was also scaled from rat volume after normalization for protein-binding differences. As such, these estimates were used to predict an efficacious human dose required for 30% lowering of triglycerides. In order to aid human dose projections, pharmacokinetic/pharmacodynamic relationships for triglyceride lowering by 1 were first established in mice, which allowed an insight into the efficacious concentrations required for maximal triglyceride lowering. Assuming that the pharmacology translated in a quantitative fashion from mouse to human, dose projections were made for humans using mouse pharmacodynamic parameters and the predicted human pharmacokinetic estimates. First-in-human clinical studies on 1 following oral administration suggested that the human pharmacokinetics/dose predictions were in the range that yielded a favourable pharmacodynamic response.


Assuntos
Benzoatos/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , PPAR alfa/agonistas , Administração Oral , Animais , Benzoatos/química , Benzoatos/farmacologia , Células CACO-2 , Permeabilidade da Membrana Celular/efeitos dos fármacos , Inibidores das Enzimas do Citocromo P-450 , Avaliação Pré-Clínica de Medicamentos , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Humanos , Injeções Intravenosas , Macaca fascicularis , Taxa de Depuração Metabólica , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley , Triglicerídeos/antagonistas & inibidores , Triglicerídeos/sangue
13.
Pharmacogenomics J ; 8(6): 408-15, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18253135

RESUMO

Our objective was to determine if beta(1)-adrenergic receptor (beta(1)-AR) and beta(2)-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during dobutamine stress echocardiography (DSE). Patients (n=163) undergoing clinically indicated DSE were enrolled. Dobutamine doses were titrated from 5 to 40 microg kg(-1) min(-1) at 3 min intervals and HR, SBP and DBP were measured. Genotypes were determined for beta(1)-AR Ser49Gly, beta(1)-AR Arg389Gly, beta(2)-AR Arg16Gly and beta(2)-AR Gln27Glu polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis, pyrosequencing and single primer extension methods. beta(2)-AR Glu27 homozygotes had a greater HR response at the highest dobutamine dose than Gln27 carriers (P=0.002). Beta(2)-AR Gly16 homozygotes had a lower HR response during 5-30 microg kg(-1) min(-1) of the dobutamine infusion protocol compared to Arg16 carriers (P=0.03). Differences in SBP by beta(2)-AR codon 16 genotype and DBP by beta(1)-AR codon 389 genotype were found at baseline and were maintained throughout DSE (P=0.06 and 0.02, respectively). However, the magnitude of SBP and DBP response to dobutamine did not differ significantly by beta(2)-AR codon 16 or beta(1)-AR codon 389 genotypes, respectively. These data suggest that the four selected beta(1)- and beta(2)-AR polymorphisms do not substantially influence the magnitude of hemodynamic response to dobutamine during DSE.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dobutamina/administração & dosagem , Ecocardiografia/métodos , Frequência Cardíaca/efeitos dos fármacos , Polimorfismo Genético , Receptores Adrenérgicos beta/genética , Idoso , Estudos de Coortes , Dobutamina/farmacologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
14.
Diabetologia ; 49(12): 2892-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17096118

RESUMO

AIMS/HYPOTHESIS: Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. METHODS: We examined the relationship between variation at the C311S and A148G polymorphisms (together with PON2 intronic variant rs12704795) and indices of renal dysfunction (progression to micro- and macroalbuminuria, plasma creatinine increases) in 3,374 newly diagnosed type 2 diabetic subjects from the UK Prospective Diabetes Study followed prospectively (median 14.0 years), using proportional hazards models, adjusted for sex, ethnicity and other known or putative risk factors. RESULTS: rs12704795 genotypes were associated with differing rates of development of microalbuminuria (relative risk [RR] for CC vs AA homozygotes 0.68 [95% CI 0.54-0.87], p=0.002) but not other measures of worsening renal function. Heterozygotes for C311S were more likely to develop microalbuminuria (RR=1.31 [95% CI 1.11-1.54], p=0.001) but less likely to double creatinine levels during follow-up (RR=0.49 [95% CI 0.27-0.89], p=0.02). There was no corroboration of this latter association for related outcomes and no prior evidence supports heterosis effects at this locus. CONCLUSIONS/INTERPRETATION: We conclude that the PON2 variants typed in this study have, at best, a small effect on the risk of renal dysfunction in type 2 diabetes.


Assuntos
Arildialquilfosfatase/genética , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Polimorfismo Genético , Albuminúria/genética , Substituição de Aminoácidos , Pressão Sanguínea , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/enzimologia , Progressão da Doença , Etnicidade , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
15.
Int J Obes (Lond) ; 29(7): 746-54, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15917856

RESUMO

OBJECTIVES: The beta-adrenergic receptor (betaAR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the beta(1)AR (ADRB1), beta(2)AR (ADRB2), beta(3)AR (ADRB3), Gs protein alpha (GNAS1), to which all three beta-receptors couple and the G protein beta3 subunit (GNB3), to which beta(3)ARs couple. DESIGN: A case-control genetic association study. SUBJECTS: A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation (WISE) study. MEASUREMENTS: Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made. RESULTS: Polymorphisms in the three betaAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity. CONCLUSIONS: Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the betaARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women.


Assuntos
Obesidade/genética , Polimorfismo Genético , Receptores Adrenérgicos beta/genética , Receptores Acoplados a Proteínas G/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Índice de Massa Corporal , Estudos de Coortes , Feminino , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/metabolismo , População Branca
16.
Arq. bras. med. vet. zootec ; 57(1): 133-135, fev. 2005. tab
Artigo em Português | LILACS | ID: lil-403222

RESUMO

The interaction between ivermectin-resistant and ivermectin-sensitive nematodes and the effect of this anthelmintic on the hematological status of naturally infected goats was assessed using 36 animals. Of these animals, 12 were infected by ivermectin-sensitive gastrointestinal nematodes of the superfamily Trichostrongyloidea (G1s e G1s) 12 were infected by ivermectin-resistant nematodes (G2r e G2r) and 12 uninfect goats (G3np). Six infected goats of each group (G1sm e G2rm) received oral ivermectin al the dose of 200µg/kg, while six were used as controls (G1sc e G2rc). Blood and fecal samples were collected on the day of medication (day zero), at seven, and at 14 days thereafter. The erythrocyte count and hematocrit levels in goats infected by sensitive strains of Haemonchus was greater than that of the group infected by a resistant strain. These values are lower in comparison to those observed in uninfected goats. The increase in the number of eggs per gram of feces, regardless of the strain, is inversely related to the hematocrit level. The use of ivermectin did not significantly change the hematological parameters of goats.


Assuntos
Animais , Cabras/parasitologia , Cabras/sangue , Haemonchus/patogenicidade , Ivermectina/uso terapêutico , Nematoides/patogenicidade , Helmintos/patogenicidade
17.
Artigo em Inglês | MEDLINE | ID: mdl-15552718

RESUMO

Mite allergen exposure has been widely related to sensitization and development of allergic diseases. This study intended to evaluate the degree of allergen exposure in Uberaba, Brazil, through the measurements of Der f 1 and Der p 1 allergen levels associated with the acarologic analysis in house dust samples. A total of 240 dust samples were collected from 60 houses through vacuuming sofas and bedding, during the months of March and July 2000. Indoor temperature and relative humidity were also measured. Mites were counted and identified under light microscopy and allergen levels were measured by two-site monoclonal antibody ELISAs. The major mite family was Pyroglyphidae (39.4%), having D. pteronyssinus as the most frequent species (15.6%), followed by D. farinae (12.3%) and E. maynei (7.9%). The family Glycyphagidae was less commonly found (4.8%), with Blomia tropicalis (4.4%) as its majoritary member. The highest levels of Der f 1 and Der p 1 allergens were found in bedding samples in March (31.7 and 0.9 microg/g of dust, respectively), with Der f 1 levels significantly higher than Der p 1 (p < 0.0001). There was a significant positive correlation between the mite number and allergen levels. These results indicate that Dermatophagoides sp are the most frequent mites in our region followed by E. maynei. Therefore, the knowledge of the local mite fauna would improve the means of investigating the association between allergen exposure and sensitization, allowing the addition of new mite extracts in diagnostic tests.


Assuntos
Poluição do Ar em Ambientes Fechados , Alérgenos/análise , Antígenos de Dermatophagoides/análise , Exposição Ambiental , Alérgenos/classificação , Antígenos de Dermatophagoides/imunologia , Brasil/epidemiologia , Monitoramento Ambiental , Ensaio de Imunoadsorção Enzimática , Monitoramento Epidemiológico , Humanos , Probabilidade , Fatores de Risco , Estatísticas não Paramétricas
18.
J Dairy Sci ; 87(4): 816-30, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15259216

RESUMO

Raw milk from 13 cows fed TMR supplemented with native pasture and from 13 cows fed only TMR on one farm was collected separately 4 times with an interval of 15 d between collections. Two blocks (14 kg each) of cheese were made from each milk. The objective was to determine the influence of consumption of native plants in Sicilian pastures on the aroma compounds present in Ragusano cheese. Milk from cows that consumed native pasture plants produced cheeses with more odor-active compounds. In 4-mo-old cheese made from milk of pasture-fed cows, 27 odor-active compounds were identified, whereas only 13 were detected in cheese made from milk of total mixed ration-fed cows. The pasture cheeses were much more rich in odor-active aldehyde, ester, and terpenoid compounds than cheeses from cows fed only total mixed ration. A total of 8 unique aroma-active compounds (i.e., not reported in other cheeses evaluated by gas chromatography olfactory) were detected in Ragusano cheese made from milk from cows consuming native Sicilian pasture plants. These compounds were 2 aldehydes ([E,E]-2,4-octadienal and dodecanal), 2 esters (geranyl acetate and [E]-methyl jasmonate), 1 sulfur compound (methionol), and 3 terpenoid compounds (1-carvone, L(-) carvone, and citronellol). Geranyl acetate and (E)-methyl jasmonate were particularly interesting because these compounds are released from fresh plants as they are being damaged and are part of a possible plant defense mechanism against damage from insects. Most of the odor-active compounds that were unique in Ragusano cheese from pasture-fed cows appeared to be compounds created by oxidation processes in the plants that may have occurred during foraging and ingestion by the cow. Some odor-active compounds were consistently present in pasture cheeses that were not detected in the total mixed ration cheeses or in the 14 species of pasture plants analyzed. Either these compounds were present in other plants not analyzed, created in the rumen or in cheese after the pasture-plant material had been consumed, or the compounds were lost in the method of sample extraction used for the plant analysis (i.e., steam distillation) versus the solid-phase microextraction method used for the cheeses. This research has demonstrated clearly that some unique odor-active compounds found in pasture plants can be transferred to the cheese.


Assuntos
Ração Animal , Bovinos , Queijo/análise , Odorantes/análise , Animais , Cromatografia Gasosa , Dieta , Ácidos Graxos não Esterificados/análise , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Plantas Comestíveis/química , Sicília , Olfato
20.
Ann Ital Chir ; 70(4): 569-73, 1999.
Artigo em Italiano | MEDLINE | ID: mdl-10573619

RESUMO

Oxygen free-radical reperfusion products play a critical role in postischemic tissues injury. In this study we used deferoxamine, an iron ligand that seems to inhibit hydroxyl radicals production, in renal normothermic acute ischemia in the rat. Our results demonstrated a significant protective effect of deferoxamine on kidneys subjected to normothermic acute ischemia.


Assuntos
Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Isquemia/prevenção & controle , Rim/irrigação sanguínea , Doença Aguda , Análise de Variância , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Isquemia/patologia , Rim/patologia , Rim/cirurgia , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
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