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1.
QJM ; 114(7): 523-524, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33734393
2.
J Intellect Disabil Res ; 63(12): 1428-1440, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31496031

RESUMO

BACKGROUND: Children with intellectual disabilities (IDs) have a severe delay in syntactic development compared with other language abilities. This study investigated conditions of syntactic development in native Japanese-speaking children with ID. METHODS: Children with ID [N = 51; 18 autism spectrum disorders (ASD), 18 Down syndrome (DS) and 15 ID without ASD and DS] were compared with typically developing children (N = 78) with the same mental age (MA). The development of syntax in spoken language was examined by receptive and production tasks. RESULTS: The development of syntax in children with ID was significantly delayed than in typically developing children with the same MA. However, when reaching the MA of 7-9, syntax abilities started to develop remarkably. Moreover, children with ASD had significant difficulties in acquiring passive voice, whereas children with DS showed a significant delay in syntactic development. CONCLUSIONS: The development of syntax in children with ID might be affected by MA and the type of disability. Moreover, it is necessary to exceed an MA of 7-9 years for children with ID to develop syntax abilities.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Deficiência Intelectual/diagnóstico , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Psicolinguística , Adolescente , Transtorno do Espectro Autista/complicações , Criança , Pré-Escolar , Síndrome de Down/complicações , Síndrome de Down/diagnóstico , Humanos , Deficiência Intelectual/complicações , Transtornos do Desenvolvimento da Linguagem/etiologia , Masculino
3.
Domest Anim Endocrinol ; 68: 54-63, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30851697

RESUMO

Here we characterized gene expressions in subcutaneous adipose tissue and blood metabolites of pigs with genetically low backfat (Landrace) and high backfat (Meishan). As pigs aged from 1 wk-to 3-mo old, mRNA levels of adipose-specific genes increased, although their gene expressions coding for major enzymes involved in lipid metabolism (lipoprotein lipase, fatty acid synthase, and hormone-sensitive lipase) did not differ between lean and fat pigs. Instead, there were significant effects for adiponectin and its receptor AdipoR1 mRNA levels between the two breeds of which respective expressions were lower and higher in Meishan by 3 mo of age. Contrary to changes in gene expressions, the concentrations of blood glucose, triglyceride (TG), and NEFA in both breeds decreased during growth, and 3-mo-old Meishan evidenced lower glucose with higher TG than the Landrace. The homeostasis model assessment insulin resistance (HOMA-IR) index was also calculated from the measurements of fasting glucose and insulin concentration, and Meishan showed a higher value than the Landrace. We next examined these differences in Landrace and Meishan crossbreds, which were phenotypically distinguishable by the backfat thickness as the former lean type and the latter fat type. As with the purebreds, high backfat Meishan crosses showed the characteristics of lower glucose and higher TG in circulating levels and also lower adiponectin transcripts in subcutaneous adipose tissue. Collectively, our results demonstrate that levels of adiponectin and its receptor gene expressions, blood glucose, blood lipids, and HOMA-IR in pigs vary between lean and fat. These observations strongly suggest the possibility that overall metabolic differences rather than adipocyte ability itself contribute to the fatness of genetically high backfat pigs.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/fisiologia , Composição Corporal/genética , Regulação da Expressão Gênica/fisiologia , Receptores de Adiponectina/metabolismo , Suínos/genética , Adiponectina/genética , Animais , Glicemia , Composição Corporal/fisiologia , Cruzamentos Genéticos , Feminino , Insulina/sangue , Insulina/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Adiponectina/genética , Suínos/fisiologia
4.
J Nutr Health Aging ; 21(6): 710-714, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28537337

RESUMO

BACKGROUND: Aging anorexia, defined as loss of appetite and/or reduced food intake, has been postulated as a risk factor for frailty. Impairments of taste and smell perception in elderly people can lead to reduced enjoyment of food and contribute to the anorexia of aging. OBJECTIVE: To evaluate the relationship between frailty and taste and smell perception in elderly people living in urban areas. DESIGN: Data from the baseline evaluation of 768 residents aged ≥ 65 years who enrolled in a comprehensive geriatric health examination survey was analyzed. Fourteen out of 29-items of Appetite, Hunger, Sensory Perception questionnaire (AHSP), frailty, age, sex, BMI, chronic conditions and IADL were evaluated. AHSP was analyzed as the total score of 8 taste items (T) and 6 smell items (S). Frailty was diagnosed using a modified Fried's frailty criteria. RESULTS: The area under the receiver operator curves for detection of frailty demonstrated that T (0.715) had moderate accuracy, but S (0.657) had low accuracy. The cutoffs, sensitivity, specificity and Youden Index (YI) values for each perception were T: Cutoff 26.5 (YI: 0.350, sensitivity: 0.639, specificity: 0.711) and S: Cutoff 18.5 (YI: 0.246, sensitivity: 0.690, specificity: 0.556). Results from multiple logistic regression models, after adjusting for age, sex, IADL and chronic conditions showed that participants under the T cutoff were associated with exhaustion and those below the S cutoff were associated with slow walking speed. The adjusted logistic models for age, sex, IADL and chronic conditions showed significant association between T and frailty (OR 2.81, 95% CI 1.29-6.12), but not between S and frailty (OR 1.73, 95% CI 0.83-3.63). CONCLUSIONS: Taste and smell perception, particularly taste perception, were associated with a greater risk of frailty in community-dwelling elderly people. These results suggest that lower taste and smell perception may be an indicator of frailty in old age.


Assuntos
Envelhecimento/fisiologia , Apetite/fisiologia , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Fome/fisiologia , Sensação/fisiologia , Olfato/fisiologia , Paladar/fisiologia , Idoso , Idoso de 80 Anos ou mais , Anorexia , Fadiga , Feminino , Humanos , Masculino , Percepção/fisiologia , Fatores de Risco , Inquéritos e Questionários
5.
Vitam Horm ; 104: 19-28, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28215295

RESUMO

One of the most characterized neurotrophic factors is brain-derived neurotrophic factor (BDNF), which regulates neuronal survival and differentiation, and functions in activity-dependent plasticity processes such as long-term potentiation, long-term depression (LTD), and learning memory. Similar to other growth factors, BDNF protein is produced by transcriptional and translational mechanisms. Nevertheless, a posttranslational mechanism, the proteolytic conversion of precursor BDNF into at least two fragments, bioactive BDNF and the prodomain, has not been well elucidated. Recently, we demonstrated that the BDNF prodomain, which is named the BDNF propeptide, was endogenously secreted from neuronal cells and facilitated a cellular mechanism of LTD, suggesting the manner through which this posttranslational mechanism multiplies the biological actions of BDNF. In this chapter, we focus on the BDNF propeptide, especially in synaptic plasticity, and discuss the role of this molecule in the brain. The findings regarding the BDNF propeptide would provide new insights for understanding the mechanisms of action of the propeptides of growth factors as well as the biological roles of neurotrophins.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Plasticidade Neuronal , Precursores de Proteínas/metabolismo , Substituição de Aminoácidos , Animais , Fator Neurotrófico Derivado do Encéfalo/química , Fator Neurotrófico Derivado do Encéfalo/genética , Humanos , Depressão Sináptica de Longo Prazo , Neurônios/citologia , Neurônios/metabolismo , Polimorfismo Genético , Domínios e Motivos de Interação entre Proteínas , Precursores de Proteínas/química , Precursores de Proteínas/genética , Vesículas Secretórias/metabolismo , Transmissão Sináptica
6.
Phys Med Biol ; 60(16): 6273-88, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26237580

RESUMO

Measurement of the dielectric properties of ocular tissues up to 110 GHz was performed by the coaxial probe method. A coaxial sensor was fabricated to allow the measurement of small amounts of biological tissues. Four-standard calibration was applied in the dielectric property measurement to obtain more accurate data than that obtained with conventional three-standard calibration, especially at high frequencies. Novel data of the dielectric properties of several ocular tissues are presented and compared with data from the de facto database.


Assuntos
Técnicas Eletroquímicas/instrumentação , Olho/efeitos da radiação , Micro-Ondas/efeitos adversos , Ondas de Rádio/efeitos adversos , Animais , Técnicas Eletroquímicas/métodos , Humanos , Coelhos
7.
Transl Psychiatry ; 5: e596, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26151924

RESUMO

Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's ρ = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's ρ = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Ácidos Docosa-Hexaenoicos/uso terapêutico , Precursores de Proteínas/sangue , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Depressão/sangue , Depressão/prevenção & controle , Método Duplo-Cego , Ácido Eicosapentaenoico/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Transtornos de Estresse Pós-Traumáticos/sangue , Ferimentos e Lesões/psicologia , Adulto Jovem
8.
J Anim Sci ; 93(6): 2778-84, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26115265

RESUMO

The hyperinsulinemic-euglycemic clamp (EGC) technique was used to investigate the effects of calcium salts of long-chain fatty acids (LCFA-Ca) and rumen-protected Met (RPM) on insulin sensitivity in the peripheral tissues of lactating cows. Six multiparous Holstein cows were used in a 3 × 3 Latin square experiment in each 14-d period. Dietary treatments were 0 (RPM0), 20 (RPM20), and 60 (RPM60) g/d of RPM, supplemented with a diet containing 1.5% of LCFA-Ca equal to 110% of the cows' ME requirement. And as a control for the 3 LCFA-Ca-containing diets, a dietary treatment without LCFA-Ca (Con) was also included. After a 10-d adaptation period, milk samples were collected for 4 d, and EGC experiments were performed on d 14 of each treatment period. Insulin solution was infused through a jugular vein catheter at a rate of 0.1, 0.2, 0.3, and 0.4 milliunits·kg BW-1·min-1 for 30 min and then at a rate of 0.5 milliunits·kg BW-1·min-1 for 60 min. Glucose solution was variably infused to maintain plasma glucose at steady state through the same catheter. Blood samples for measurements were taken using the contralateral catheter. Plasma total cholesterol, cholesterol ester, free cholesterol, and phospholipid concentrations in RPM0 and RPM20 were higher than those in Con, whereas the concentrations in RPM60 were low at the same degree of those in RPM0 (P < 0.05). Plasma Met concentration was greatest in RPM60 (P < 0.05). In the EGC experiment, the glucose infusion rate was greater in RPM60 than in RPM0 and RPM20 and an effective concentration of insulin resulting in 50% maximal glucose infusion rate was lower in RPM60 compared with RPM0 (P < 0.05), indicating that insulin sensitivity was intensified in RPM60. Although the insulin sensitivity evaluated from the EGC data in RPM0, RPM20, and RPM60 was not different from Con, a slight decline was observed in RPM0 and insulin sensitivity in RPM60 was higher than Con. Our results from the EGC experiment demonstrated that the feeding RPM lead to increased insulin sensitivity, which suggests that dietary Met affects lipid metabolism via insulin action in lactating dairy cows fed a LCFA-Ca-containing diet.


Assuntos
Dieta Hiperlipídica/veterinária , Gorduras na Dieta/farmacologia , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metionina/farmacologia , Animais , Bovinos , Colesterol/sangue , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Ácidos Graxos/metabolismo , Feminino , Glucose/administração & dosagem , Insulina/administração & dosagem , Insulina/sangue , Lactação/fisiologia , Metionina/sangue , Leite/metabolismo , Rúmen/metabolismo
9.
J Biol Regul Homeost Agents ; 29(1): 51-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25864741

RESUMO

It is important to determine the immunological properties for the maintenance of health. We chose the Shikoku Walking Pilgrimage to assess the proper biomarkers for the evaluation of immunological properties. We examined whether the Shikoku Walking Pilgrimage could have a positive effect on the mental and physical health of walking participants by using several biomarkers proposed by our laboratory. Twelve non-randomized healthy male volunteers including 3 twice attendees walked the Shikoku Walking Pilgrimage distance of 58.9 km over 3 days. Plasma, serum, urine, and saliva were collected from the volunteers during the pilgrimage and at 1 week before and after it. Immunological biomarkers, including lipid metabolism, oxidative stress, immune function, and catecholamines, were measured. Additionally, mood state scores, alertness, autonomic nervous system activity, and body motion levels during sleep were assessed. A significant decrease was observed in the subjective tension-anxiety levels and in the concentrations of serum low-density lipoprotein cholesterol, plasma hydroxyoctadecadienoic acid (HODE), and urine adrenaline during the pilgrimage as compared to the values of these parameters before the participants embarked on the pilgrimage. The serum levels of brain-derived neurotrophic factor (BDNF) were significantly increased 1 week after the pilgrimage relative to those assessed previously. No significant differences in subjective fatigue and the flicker perception threshold were observed. These results suggest that the Shikoku Walking Pilgrimage can exert a positive effect on mental and physical health as particularly shown in the reduction of tensionanxiety and oxidative stress without the accompaniment of fatigue. HODE correlated significantly with typical immunological marker natural killer cell activity and immunoglobulin G. This suggests that there are promising biomarkers such as HODE, NK activity, BDNF, LDL-c, and IgG for assessing the immunological properties.


Assuntos
Biomarcadores/análise , Sistema Imunitário/fisiologia , Caminhada/fisiologia , Caminhada/psicologia , Adulto , Afeto/fisiologia , Ansiedade/imunologia , Ansiedade/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Fator Neurotrófico Derivado do Encéfalo/sangue , LDL-Colesterol/sangue , Epinefrina/urina , Fadiga/imunologia , Ácidos Graxos Insaturados/sangue , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
11.
Br J Cancer ; 111(12): 2229-34, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25255100

RESUMO

BACKGROUND: The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies. OBJECTIVE: The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base. METHODS: Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m(-2) of CDDP was superselectively administered weekly to each feeding artery including ICA four times. RESULTS: The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable. CONCLUSIONS: This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias dos Seios Paranasais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade
12.
Domest Anim Endocrinol ; 45(4): 216-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24209506

RESUMO

The purpose of this study was to elucidate the effects of medium-chain fatty acids (MCFAs) on plasma ghrelin concentration in lactating dairy cows. Five early-lactating Holstein cows were randomly assigned to 2 dietary treatments in a crossover design with 2-wk periods. Treatments consisted of diets supplemented or not (control) with calcium salts of MCFAs (MCFA-Ca; 1.5% dry matter). Plasma hormone and metabolite concentrations in blood samples taken from the jugular vein were measured on the morning of feeding on day 14 of each period. Dry matter intake, milk protein, and lactose content of cows fed the MCFA-Ca diet were decreased compared with controls, but with no change in milk yield. Plasma ghrelin concentrations were higher in cows fed the MCFA-Ca diet; however, no significant effect was found on glucagon-like peptide-1 concentrations in plasma. Plasma insulin concentrations decreased, but plasma glucagon concentrations remained unchanged in cows fed the MCFA-Ca diet. The concentrations of nonesterified FAs, total cholesterol, and ß-hydroxybutyrate in plasma increased in these cows. In conclusion, dietary MCFAs increase the plasma ghrelin concentrations in lactating dairy cows.


Assuntos
Bovinos/fisiologia , Dieta/veterinária , Ácidos Graxos/administração & dosagem , Grelina/sangue , Lactação/fisiologia , Ácido 3-Hidroxibutírico/sangue , Animais , Glicemia/análise , Estudos Cross-Over , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Ácidos Graxos/análise , Ácidos Graxos não Esterificados/sangue , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Insulina/sangue , Leite/química
13.
Osteoarthritis Cartilage ; 21(6): 831-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23523852

RESUMO

OBJECTIVE: To determine whether differences in synovial fluid (SF) biomarkers of collagen and proteoglycan turnover are associated with pre-radiographic damage to articular cartilage and menisci following anterior cruciate ligament (ACL) injury and are of clinical value. METHOD: SF samples from ACL injured knees of 108 patients were obtained when damage to cartilages and menisci was evaluated arthroscopically. Concentrations of SF collagenase-generated cleavage neoepitope of type II collagen (C2C) were determined using ELISA and aggrecan-derived disaccharides of chondroitin-4-sulfate (Δdi-C4S), chondroitin-6-sulfate (Δdi-C6S), and keratan sulfate (KS), were measured in SF by High performance liquid chromatography (HPLC). RESULTS: Radiographic examination failed to detect any intra-articular degenerative changes. The number of high-grade cartilage lesions was positively associated with age, duration after injury and the level of C2C, and negatively with the level of KS. There was no association between the number of high-grade cartilage and meniscal lesions. Multivariable logistic regression revealed significant associations of increased C2C (adjusted Odds ratio (OR) of the upper quartile to remainder of 2.49, 95% Confidence interval (CI) = 0.85-7.27) and decreased KS (adjusted OR of the lower quartile to the remainder of 3.32, 95% CI = 1.19-9.24) with the presence of three or more high-grade cartilage lesions, independent of age and duration after injury. The combined impact of increased C2C and decreased KS was 22.8 (95% CI = 1.95-265.9), far exceeding the impact of each independent biomarker. CONCLUSION: Combinations of the C2C and KS as described here may offer greater ability to identify patients with early pre-radiographic high-grade cartilage damage compared to single clinical or biomarker parameters.


Assuntos
Ligamento Cruzado Anterior/metabolismo , Cartilagem Articular/metabolismo , Meniscos Tibiais/metabolismo , Líquido Sinovial/química , Adolescente , Adulto , Agrecanas/análise , Lesões do Ligamento Cruzado Anterior , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Cromatografia Líquida de Alta Pressão , Colágeno Tipo II/análise , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Sulfato de Queratano/análise , Modelos Logísticos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Proteoglicanas/análise , Radiografia , Lesões do Menisco Tibial , Adulto Jovem
15.
Environ Toxicol ; 28(1): 21-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21384493

RESUMO

Chlorinated benz[a]anthracenes (Cl-BaA) are halogenated aromatic compounds (typified by dioxins) found in the environment at relatively high concentrations. Fischer 344 rats were intragastrically administered 0, 1, or 10 mg of Cl-BaA or its parent compound benz[a]anthracene (BaA) per kg of body weight for 14 consecutive days. Both chemicals at 10 mg/kg/day inhibited the gain in body weight, and consequent increase in relative liver weight. Hepatic gene expression of cytochrome P450 (CYP) 1A1, 1A2, and 1B1 was significantly stimulated by administration of BaA (10 mg/kg/day) compared with the control. After administration of Cl-BaA, only the CYP1A2 gene was significantly induced, even at the lower dosage; CYP1A1 and 1B1 mRNA levels remained unchanged in Cl-BaA-treated rats compared with controls. To elucidate the role of such Cl-BaA exposure and induced CYPs at toxicity onset, we investigated the mutagenicity of BaA and Cl-BaA using Salmonella typhimurium TA98 and TA100. BaA and Cl-BaA at 10 µg/plate produced positive results in both strains in the presence of rat S-9. Incubation of Cl-BaA with recombinant rat CYP1A2 produced a significantly higher number of revertant colonies in TA98 and TA100 than in controls, but no such change was observed for BaA. In conclusion, BaA changes its own physiological and toxicological actions by its chlorination; (1) daily exposure to Cl-BaA selectively induces hepatic CYP1A2 in rats and (2) Cl-BaA induces frameshift mutations in the presence of CYP1A2, although BaA does not exert mutagenicity. This indicates that CYP1A2 may metabolize Cl-BaA to active forms.


Assuntos
Benzo(a)Antracenos/toxicidade , Fígado/efeitos dos fármacos , Mutagênicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP1B1 , Citocromos/metabolismo , Mutação da Fase de Leitura , Regulação da Expressão Gênica/efeitos dos fármacos , Halogenação , Fígado/metabolismo , Masculino , Testes de Mutagenicidade , Ratos , Ratos Endogâmicos F344 , Salmonella typhimurium/metabolismo
16.
J Anim Sci ; 90(13): 4839-45, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22871932

RESUMO

The effects of feeding and intravenous injections of glucose and VFA on blood ghrelin concentrations were investigated in calves before and after weaning. Eight Holstein bull calves were fed whole milk, allowed free access to solid feeds, and weaned at 7 wk. Measurements were carried out at 2, 4, 6, 9, 11, and 13 wk, at which time jugular blood samples were taken from 4 calves through a catheter from 10 min before to 120 min after their morning feed at 10 min intervals (Exp. 1). An additional 4 calves of the same age were intravenously injected with glucose (1.0 mmol·kg BW(-1)) and a solution of VFA (2.4 mmol·kg BW(-1), acetate:propionate:butyrate in a 6:3:1 ratio) using a catheter, and jugular blood samples were taken temporally relative to the injection time (Exp. 2). In Exp. 1, blood ghrelin concentrations decreased (P < 0.05) after feeding at all ages. However, preprandial ghrelin concentrations were less (P = 0.025) and the degree of postprandial depression of ghrelin tended to be greater during the postweaning period (P = 0.084) than during the preweaning period. Blood glucose concentrations increased after feeding during the preweaning period (P < 0.05), whereas blood acetate concentrations increased during the postweaning period (P < 0.05). In Exp. 2, injection of VFA induced a greater decrease in blood ghrelin concentrations than glucose injection throughout the entire period (P < 0.05). These results indicate that weaning reduces the basal concentration of blood ghrelin because the circulating VFA derived from ruminal fermentation may more strongly depress blood ghrelin concentrations than glucose.


Assuntos
Bovinos/fisiologia , Ácidos Graxos Voláteis/administração & dosagem , Grelina/sangue , Glucose/administração & dosagem , Desmame , Envelhecimento , Animais , Injeções Intravenosas/veterinária , Masculino
17.
Transplant Proc ; 44(5): 1329-35, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22664010

RESUMO

We investigated the pharmacokinetics of mizoribine in the acute phase after adult living donor liver transplantation (LDLT). Between February 2004 and October 2009, 16 recipients received immunosuppressive therapy that included mizoribine (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after administration on postoperative days 3, 7, and 21. We assessed area under the concentration time curve (AUC) (hour · µg/mL), normalized serum concentration (NSC) at C0 [concentration (µg/mL)/dose (mg/kg body weight)], and estimated glomerular filtration rate (eGFR). The mizoribine concentration showed increases at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3 in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0 increased for 3 weeks after LDLT. There was a significant correlation between the NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations between the NSC at C0 and either aspartate aminotransferase, total bilirubin, albumin, trough cyclosporine, or trough tacrolimus on any day. The pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected by postoperative day and renal function.


Assuntos
Imunossupressores/farmacocinética , Transplante de Fígado , Doadores Vivos , Ribonucleosídeos/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Japão , Rim/fisiopatologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/sangue , Resultado do Tratamento
18.
Br J Cancer ; 107(2): 340-4, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22617127

RESUMO

BACKGROUND: KRAS mutations are predictive markers for the efficacy of anti-EGFR antibody therapies in patients with metastatic colorectal cancer. Although the mutational status of KRAS is reportedly highly concordant between primary and metastatic lesions, it is not yet clear whether genotoxic chemotherapies might induce additional mutations. METHODS: A total of 63 lesions (23 baseline primary, 18 metastatic and 24 post-treatment metastatic) from 21 patients who were treated with FOLFOX as adjuvant therapy for stage III/IV colorectal cancer following curative resection were examined. The DNA samples were obtained from formalin-fixed paraffin-embedded specimens, and KRAS, NRAS, BRAF and PIK3CA mutations were evaluated. RESULTS: The numbers of primary lesions with wild-type and mutant KRAS codons 12 and 13 were 8 and 13, respectively. The mutational status of KRAS remained concordant between the primary tumours and the post-FOLFOX metastatic lesions, irrespective of patient background, treatment duration and disease-free survival. Furthermore, the mutational statuses of the other genes evaluated were also concordant between the primary and metastatic lesions. CONCLUSION: Because the mutational statuses of predictive biomarker genes were not altered by FOLFOX therapy, specimens from both primary tumours and post-FOLFOX tumour metastases might serve as valid sources of DNA for known genomic biomarker testing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Fluoruracila/uso terapêutico , Genes ras , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)
19.
Domest Anim Endocrinol ; 42(2): 74-82, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22056209

RESUMO

Our objective was to determine the effects of calcium salts of long-chain fatty acids (CLFAs) and rumen-protected methionine (RPM) on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide, and pancreatic hormones in lactating cows. Four Holstein cows in midlactation were used in a 4 by 4 Latin square experiment in each 2-wk period. Cows were fed corn silage-based diets with supplements of CLFAs (1.5% added on dry matter basis), RPM (20 g/d), CLFAs plus RPM, and without supplement. Jugular blood samples were taken from 1 h before to 2 h after morning feeding at 10-min intervals on day 12 of each period. CLFAs decreased dry matter intake, but RPM did not affect dry matter intake. Both supplements of CLFAs and RPM did not affect metabolizable energy intake and milk yield and composition. Plasma concentrations of NEFAs, triglyceride (TG), and total cholesterol (T-Cho) were increased with CLFAs alone, but increases of plasma concentrations of TG and T-Cho were moderated by CLFAs plus RPM. Calcium salts of long-chain fatty acids increased plasma ghrelin concentration, and the ghrelin concentration with CLFAs plus RPM was the highest among the treatments. Plasma concentrations of glucagon-like peptide-1, glucagon, and insulin were decreased with CLFAs, whereas adding RPM moderated the decrease of plasma glucagon concentration by CLFAs. These results indicate that the addition of methionine to cows given CLFAs increases plasma concentrations of ghrelin and glucagon associated with the decrease in plasma concentrations of TG and T-Cho.


Assuntos
Cálcio/administração & dosagem , Bovinos/metabolismo , Ácidos Graxos/administração & dosagem , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Metionina/administração & dosagem , Fragmentos de Peptídeos/sangue , Animais , Colesterol/sangue , Suplementos Nutricionais , Ácidos Graxos não Esterificados/sangue , Feminino , Lactação/efeitos dos fármacos , Análise dos Mínimos Quadrados , Leite/química , Leite/metabolismo , Triglicerídeos/sangue
20.
Domest Anim Endocrinol ; 42(2): 83-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22056236

RESUMO

Growth hormone secretion from the anterior pituitary gland is controlled by interactions between three hormone receptors, between GHRH and GHRH receptor (GHRH-R), between ghrelin and growth hormone secretagogue receptor (GHS-R1a), and between somatostatin and somatostatin receptors in the hypothalamus and anterior pituitary gland. Ghrelin-GHS-R1a is involved in many important functions, including GH secretion and appetite. We investigated age-related changes in the expressions of GHS-R1a, GHS-R1b (the truncated-type receptor), and GHRH-R mRNAs by real-time reverse transcription-PCR using 16 tissues, leukocytes, oocytes, and cumulus cells in Holstein-Friesian cattle. The tissue samples were divided into three age classes: 1) 19 to 26 d of age (preweaning calves), 2) 2 mo to 6.5 mo of age (postweaning calves), and 3) 3.2 to 8.1 yr of age (cows). The GHS-R1a mRNA was highly (P < 0.05) expressed in the arcuate nucleus, pituitary gland, and liver compared with that of the other tissues in all age classes. Expression of GHS-R 1a mRNA in the arcuate nucleus of postweaning calves was > 10-fold greater (P < 0.01) than those of preweaning calves and cows, and its expression level was the greatest (P < 0.01) in all tissues examined in age group 2. GHS-R1a and GHRH-R mRNA expressions in the pituitary gland of preweaning calves tended to be greater (P < 0.20 and P < 0.17, respectively) than those of postweaning calves and cows. GHS-R1b mRNA expression was detected in all tissues examined, and abundance was greater (P < 0.05) in the pancreas, pituitary gland, spleen, arcuate nucleus, adipose tissue, and leukocyte compared with that of the other tissues examined in age group 3. Interestingly, a relatively large animal-to-animal variation was observed in pancreas GHS-R 1b mRNA expression. The GHRH-R mRNA was markedly increased (P < 0.01) in the pituitary gland in all age groups compared with that of the other tissues. GHRH-R mRNA abundance in the arcuate nucleus, pituitary gland, liver, spleen, adipose tissue, and heart of preweaning calves tended to be greater than those of postweaning calves and cows. The GHRH-R mRNA was not detected in the mammary gland and adipose tissue of nonlactating cows.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiologia , Bovinos/genética , Regulação da Expressão Gênica , Hormônio do Crescimento/biossíntese , Adeno-Hipófise/fisiologia , Receptores de Grelina/biossíntese , Receptores de Neuropeptídeos/biossíntese , Receptores de Hormônios Reguladores de Hormônio Hipofisário/biossíntese , Fatores Etários , Animais , Bovinos/metabolismo , Feminino , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Análise dos Mínimos Quadrados , Masculino , Adeno-Hipófise/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Receptores de Grelina/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética
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