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1.
Phys Rev Lett ; 124(25): 252501, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32639790

RESUMO

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

2.
Mol Psychiatry ; 23(8): 1717-1730, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28924188

RESUMO

Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC. Using social defeat stress (SDS) in mice, here we identified a role of dopamine D1 receptor subtype in mPFC excitatory neurons in suppressing stress susceptibility. Repeated social defeat stress (R-SDS) reduces the expression of D1 receptor subtype in mPFC of mice susceptible to R-SDS. Knockdown of D1 receptor subtype in whole neuronal populations or excitatory neurons in mPFC facilitates the induction of social avoidance by SDS. Single social defeat stress (S-SDS) induces D1 receptor-mediated extracellular signal-regulated kinase phosphorylation and c-Fos expression in mPFC neurons. Whereas R-SDS reduces dendritic lengths of mPFC layer II/III pyramidal neurons, S-SDS increases arborization and spines of apical dendrites of these neurons in a D1 receptor-dependent manner. Collectively, our findings show that D1 receptor subtype and related signaling in mPFC excitatory neurons mediate acute stress-induced dendritic growth of these neurons and contribute to suppression of stress susceptibility. Therefore, we propose that D1 receptor-mediated dendritic growth in mPFC excitatory neurons suppresses stress susceptibility.


Assuntos
Dendritos/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D1/metabolismo , Resiliência Psicológica , Estresse Psicológico/metabolismo , Animais , Aprendizagem da Esquiva/fisiologia , Crescimento Celular , Dendritos/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças/metabolismo , Dominação-Subordinação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Córtex Pré-Frontal/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células Piramidais/metabolismo , Células Piramidais/patologia , Receptores de Dopamina D1/genética , Estresse Psicológico/patologia
3.
J Dairy Sci ; 102(2): 997-1006, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30471910

RESUMO

The probiotic Lactobacillus gasseri SBT2055 (LG2055) has a protective effect against metabolic syndrome in rats and humans. Metabolic syndrome increases the risk of type 2 diabetes mellitus. In this study, Goto-Kakizaki rats were used as a diabetic model and fed diets containing LG2055-fermented or nonfermented skim milk for 4 wk. Indices of diabetes such as blood glucose levels, serum glucagon levels, plasma levels of insulin, C-peptide, and glucagon-like peptide-1, tissue glycogen contents, and pancreatic mRNA levels were measured. The plasma C-peptide levels and pancreatic mRNA levels of insulin genes (Ins1 and Ins2) and Pdx1 (a transcriptional factor of insulin genes) were increased in LG2055 diet-fed rats. The increase in insulin secretion corresponded to an improvement in serum and pancreatic inflammatory status, associated with decreases in serum levels of serum amyloid P and pancreatic levels of granulocyte colony-stimulating factor. Insulin resistance in Goto-Kakizaki rats was ameliorated by increased glycogen storage in the liver and quadriceps femoris muscles and decreased serum free fatty acid levels. This improvement may be related to the increased cecal production of short-chain fatty acids. In conclusion, dietary LG2055 improved insulin secretion in diabetic rats by improving the inflammatory status in the pancreas and serum.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Secreção de Insulina/fisiologia , Lactobacillus gasseri , Probióticos/administração & dosagem , Animais , Glicemia/análise , Ceco/metabolismo , Dieta , Ácidos Graxos Voláteis/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue , Glicogênio/análise , Glicogênio/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Fígado/química , Masculino , Músculo Esquelético/química , Ratos
7.
Clin Exp Dermatol ; 38(1): 30-2, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22924538

RESUMO

We report a case of palmoplantar lichen planus in a 7-year-old Japanese girl with congenital deafness, who presented with erythematous eruptions and hyperkeratosis, with peeling and fissures on her soles, palms and digits. On histological examination of a skin biopsy from the lesion on her wrist, lichen planus was identified. Using computed tomography of the inner ears, bilateral cochlear dysplasia was found. The patient's DNA was sequenced; no sequence variants were detected in the GJB2 gene encoding connexin-26, but she had a missense mutation in SLC26A4 (solute carrier family 26, member 4). Mutations in SLC26A4 are known causes of hearing loss, but this is a novel mutation, which has not been reported previously. In addition, there have been no reports of cutaneous symptoms in previously reported patients with mutations in SLC26A4. To our knowledge, therefore, this is the first report of palmoplantar lichen planus associated with sensorineural deafness accompanied by a mutation in the SLC26A4 gene.


Assuntos
Dermatoses do Pé/genética , Dermatoses da Mão/genética , Perda Auditiva Neurossensorial/genética , Ceratodermia Palmar e Plantar/genética , Líquen Plano/genética , Proteínas de Membrana Transportadoras/genética , Mutação de Sentido Incorreto , Criança , Conexina 26 , Conexinas , Surdez , Feminino , Perda Auditiva Neurossensorial/congênito , Humanos , Transportadores de Sulfato
8.
Clin Otolaryngol ; 38(3): 231-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23607542

RESUMO

OBJECTIVES: Patients with peripheral facial palsy frequently complain of fluid leakage and food retention during meals. We investigated oral function during eating in adults with peripheral facial palsy. DESIGN: A prospective two-phase controlled observational study. SETTING: Data were collected at the ENT clinic in Nihon University Itabashi Hospital (patients) and Nihon University Dental Hospital (controls) between September 2009 and August 2011 and analysed at the Department of Oral Diagnostic Sciences in Nihon University School of Dentistry. PARTICIPANTS: Fourteen patients with acute idiopathic facial palsy and 14 controls completed Study 1. Sixteen patients with acute idiopathic facial palsy and 16 controls completed Study 2. MAIN OUTCOME MEASURES: In Study 1, oral vestibular cleansing capability was assessed by measuring the amount of rice remaining in the oral vestibule after mastication. In Study 2, masticatory efficiency was evaluated by measuring glucose eluted from gummy jelly during chewing. These oral functions were observed at the first visit and final visit (after patients with facial palsy had recovered). RESULTS: Oral vestibular cleansing capability at the first visit was significantly decreased by facial palsy (P < 0.001 versus healthy volunteers and P < 0.001 versus contralateral side) but recovered as facial muscular function improved (P = 0.034). There was a significant correlation between improvement in paralysis and decreased food retention (r = -0.528, P = 0.010). At the first visit, masticatory efficiency on the affected side was significantly lower than that of controls (P = 0.002) but had mostly recovered after resolution of facial palsy (P = 0.033). CONCLUSIONS: Oral functions were decreased by peripheral facial palsy. Oral vestibular cleansing capability was more significantly associated than masticatory efficiency with facial muscle function. Our data suggest that peripheral facial palsy impairs eating and worsens oral hygiene, which may result in oral disease.


Assuntos
Paralisia de Bell/fisiopatologia , Músculos Faciais/fisiopatologia , Mastigação/fisiologia , Músculos da Mastigação/fisiopatologia , Boca/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Adulto , Paralisia de Bell/complicações , Paralisia de Bell/terapia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Estudos Prospectivos
9.
Ann Oncol ; 23(8): 1973-1979, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22473594

RESUMO

BACKGROUND: Various risk factors for depression in lung cancer patients have been suggested but have been examined separately in studies with relatively small sample sizes. The present study examined the biopsychosocial risk factors of depression in lung cancer patients, focusing on psychological factors in the largest patient sample reported to date. PATIENTS AND METHODS: A total of 1334 consecutively recruited lung cancer patients were selected, and data on cancer-related variables, personal characteristics, health behaviors, physical symptoms, and psychological factors were obtained. The participants were divided into groups with or without depression using the Hospital Anxiety and Depression Scale. RESULTS: Among the recruited patients, 165 (12.4%) manifested depression. The results of a binary logistic regression analysis were significant (overall R2, 36.5%), and a greater risk for depression was strongly associated with psychological factors, such as personality characteristics (neuroticism) and coping style (low fighting spirit, helplessness/hopelessness, and anxious preoccupation). Although the contributions of cancer-related variables, personal characteristics, health behaviors, and clinical state were relatively low, cancer stage, cancer type, sex, and age correlated significantly with depression. CONCLUSION: Depression was most strongly linked with personality traits and coping style, and using screening instruments to identify these factors may be useful for preventive interventions.


Assuntos
Depressão/psicologia , Neoplasias Pulmonares/psicologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Classe Social
10.
J Dairy Sci ; 95(6): 2810-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22612918

RESUMO

Diet has a significant effect on immune and inflammatory responses. To date, no studies have described how consumption of a diet containing a relatively high amount of cheese affects immune responses and the inflammatory status of the body. We examined these responses in normal mice and mice with dextran sodium sulfate (DSS)-induced colitis associated with increased inflammatory responses, using a diet containing approximately 44% of a whole cheese powder and a diet containing casein, lard, and corn oil as the control. In normal mice, consumption of the cheese-containing diet induced regulatory T cells (T(reg)), which regulate immune and inflammatory responses, and suppressed the production of IL-17, IL-4, and IL-10 in Peyer's patch cells from the intestine. The T(reg) population and cytokine production were not altered in spleen cells. In mice with DSS-induced colitis, consumption of the cheese-containing diet alleviated the symptoms of colitis, as evidenced by prevention of body weight loss and colon length shortening, and inhibition of an increase in the disease activity index, which includes diarrhea and fecal bleeding. This relief of clinical symptoms was also associated with decreased production of proinflammatory cytokines (IL-17 and IL-6) and increased production of the antiinflammatory cytokine transforming growth factor-ß1 in Peyer's patch cells. The T(reg) population was reduced by consumption of the cheese-containing diet in Peyer's patch cells and spleen cells, which might reflect the alleviated symptoms of colitis. Consumption of the cheese-containing diet compared with the control diet enhanced antiinflammatory and immune regulatory responses in normal mice and in a DSS-colitis mouse model.


Assuntos
Queijo , Colite/prevenção & controle , Dieta , Imunidade Celular/efeitos dos fármacos , Animais , Colite/induzido quimicamente , Colite/dietoterapia , Citocinas/biossíntese , Sulfato de Dextrana/efeitos adversos , Citometria de Fluxo , Imunidade Celular/fisiologia , Inflamação/dietoterapia , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL
11.
Rhinology ; 50(2): 199-202, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22616082

RESUMO

INTRODUCTION: Juvenile angiofibromas (JA) are highly vascular, benign tumours for which surgery is the treatment of choice. In most services, embolisation is performed prior to resection. Nevertheless, there are few data on the complications of preoperative embolisation for JA. AIM: To describe major and minor complications of preoperative embolisation in a 32-year experience of patients undergoing surgical resection of JA at a tertiary hospital. METHODS: Retrospective chart review study of 170 patients who underwent surgical resection of JA at a tertiary hospital between September 1976 and July 2008. RESULTS: All patients were male. Age ranged from 9 to 26 years. Ninety-one patients had no complications after embolisation. Overall, 105 complication events occurred of which four major and 101 minor. CONCLUSION: In our series, preoperative embolisation for JA produced no irreversible complications and no aesthetic or functional sequelae. The vast majority of complications were transient and amenable to clinical management.


Assuntos
Angiofibroma/terapia , Embolização Terapêutica/efeitos adversos , Adolescente , Adulto , Angiofibroma/cirurgia , Criança , Terapia Combinada , Humanos , Masculino , Período Pré-Operatório , Adulto Jovem
12.
Science ; 250(4980): 546-9, 1990 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-2237405

RESUMO

The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Expressão Gênica , Ilhotas Pancreáticas/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , 3-O-Metilglucose , Animais , Transporte Biológico , Diabetes Mellitus/metabolismo , Feminino , Glucose/farmacologia , Immunoblotting , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Cinética , Masculino , Metilglucosídeos/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Obesidade , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Ratos Zucker
13.
Clin Genet ; 73(5): 496-501, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18363739

RESUMO

Carnitine palmitoyltransferase II (CPT II) deficiency is an inherited disorder involving beta-oxidation of long-chain fatty acids. CPT II deficiency is a wide-spectrum disorder that includes a lethal neonatal form, an infantile form, and an adult-onset form. However, the ethnic characteristics and the relationship between genotype and clinical manifestation are not well understood. We investigated three non-consanguineous Japanese patients with CPT II deficiency and examined cell lines from 4 unrelated patients and 50 healthy donors. The CPT 2 gene was typed by direct DNA sequencing of polymerase chain reaction-amplified gene products. Case 1 (infantile form) was heterozygous for a phenylalanine to tyrosine substitution at position 383 (p.F383Y) and a novel valine to leucine substitution at 605 (p.V605L). Cases 2, 4, and 5 (infantile form) and case 3 (adult-onset form) were heterozygous for a single mutation at F383Y. Case 6 (adult-onset form) was compound heterozygous at the CPT 2 locus, with deletion of cytosine and thymine at residue 408, resulting in a stop signal at 420 (p.Y408fsX420), and an arginine to cysteine substitution at position 631 (p.R631C). Case 7 (adult-onset form) was homozygous for the p.F383Y mutation. In conclusion, we identified p.F383Y mutations in six of seven patients with CPT II deficiency and two novel variants of the coding gene: p.Y408fsX420 and p.V605L. These mutations differ from those in Caucasian patients, who commonly harbor p.S113L, p.P50H, and p.Q413fsX449 mutations; therefore, our data and those of other Japanese groups suggest that the p.F383Y mutation is significant in Japanese patients with CPT II deficiency.


Assuntos
Carnitina O-Palmitoiltransferase/deficiência , Carnitina O-Palmitoiltransferase/genética , Erros Inatos do Metabolismo Lipídico/genética , Mutação , Adulto , Substituição de Aminoácidos , Povo Asiático , Criança , Pré-Escolar , Feminino , Genótipo , Heterozigoto , Humanos , Masculino
14.
Endoscopy ; 40(1): 11-5, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18058613

RESUMO

BACKGROUND AND AIM: As a tool for examining the small intestine, double-balloon enteroscopy (DBE) has been used routinely. However, there remain a few issues relating to the handling of DBE, such as attaching a balloon to the tip of the scope, and inflating/deflating the two balloon systems. Recently, we developed a novel single-balloon enteroscopy (SBE) system for the examination of the small intestine. The aim of the present study was to evaluate the insertion technique, the safety, and the clinical impact of the SBE system. PATIENTS AND METHODS: Between January 2006 and June 2007, all patients undergoing enteroscopy with the Olympus SBE system (length 200 cm, outer diameter 9.2 mm) were studied. Instead of a balloon attached to the distal scope end, the distal scope end was hook-shaped, and manipulating the up-angle or down-angle of the scope end enabled exploration of the small intestine. RESULTS: A total of 78 procedures were performed in 41 patients (24 men, 17 women; mean age 48.9 years, range 23 - 85 years). The indications for the examination were suspected mid-gastrointestinal bleeding (n = 12), Crohn's disease (n = 17), abdominal pain (n = 8), and abdominal tumor (n = 4). The mean procedure time was 62.8 +/- 20.2 minutes and 70.4 +/- 19.3 minutes for the oral and anal routes, respectively. Among 24 patients in whom total enteroscopy was attempted, the entire small intestine was explored in 6. CONCLUSION: SBE is not only easy to perform, due to the single balloon, but it can also safely examine the deep small intestine. Therefore, SBE may be a useful diagnostic and therapeutic tool in addition to DBE for investigating suspected small bowel disease.


Assuntos
Endoscopia Gastrointestinal/métodos , Enteropatias/diagnóstico , Enteropatias/terapia , Intestino Delgado , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/terapia , Dor Abdominal/diagnóstico , Dor Abdominal/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Acta Neurochir (Wien) ; 150(1): 31-9; discussion 39, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18058058

RESUMO

BACKGROUND: To evaluate our decision policy based on vertical aneurysm projection for selecting the side of the pterional approach for the surgical treatment of anterior communicating artery aneurysms. METHODS: Inferiorly projecting aneurysms were treated through the dominant A1 side, and superiorly projecting aneurysms were treated through the side of aneurysm fundus projection. We analysed postoperative outcome and surgical complications, and the correlations between the anatomical factors such as position (high or low), projection (dorsal or anterior), and the plane containing both A2 vessels (open A2 plane defined as the A2 of the approach side located more posteriorly than the contralateral A2; closed A2 plane as the ipsilateral A2 located more anteriorly than the contralateral A2), to assess the surgical requirements of approaches in patients with superiorly projecting aneurysms. FINDINGS: A favorable outcome was achieved in 95.1% of patients with inferior type aneurysms and 85.2% of patients with superior type aneurysms (P = 0.088). Surgical complications occurred in 8.9% of patients with inferior type aneurysms and 17.9% with superior type aneurysms. However, there was a distinct group of patients with superior type aneurysms characterised by a closed A2 plane, in which the ipsilateral A2 was located anterior to the contralateral A2, in whom the approach toward the neck was significantly more difficult, requiring A2 displacement or gyrus aspiration, and resulting in a neck remnant and more surgical complications such as vascular injury or cerebral contusion. This group also had a significantly high correlation with high position and dorsal projection of aneurysms causing more difficult dissection. CONCLUSIONS: This policy provided good postoperative outcomes. However, use of skull base techniques or the interhemispheric approach, instead of the normal pterional approach, may further improve the postoperative outcome for closed A2 plane aneurysms.


Assuntos
Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Feminino , Escala de Resultado de Glasgow , Humanos , Aneurisma Intracraniano/classificação , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Resultado do Tratamento
16.
J Clin Invest ; 85(3): 973-6, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2179271

RESUMO

Amylin, a peptide copackaged with insulin in beta-cell granules, was measured in the effluent of the perfused rat pancreases by means of a newly developed specific radioimmunoassay. Its secretion parallels that of insulin in response to 20 mM glucose, 10 mM arginine, or the combination thereof. The relative molar amount of secreted amylin was estimated to be 25-37% that of insulin. Treatment with a borderline diabetogenic dose of streptozotocin reduced amylin response without significantly changing the insulin response. A severely diabetogenic dose of streptozotocin totally abolished amylin release and markedly reduced insulin release. The selective impairment of amylin secretion in streptozotocin-treated rats could represent an early manifestation of beta-cell depletion or injury.


Assuntos
Amiloide/metabolismo , Diabetes Mellitus Experimental/metabolismo , Pâncreas/metabolismo , Animais , Insulina/metabolismo , Secreção de Insulina , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Ratos , Ratos Endogâmicos
17.
J Clin Invest ; 86(5): 1615-22, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2243134

RESUMO

Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transporter of beta-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT-2-positive to insulin-positive beta-cells was only 0.48 +/- 0.06, compared to 0.91 +/- 0.02 in age-matched nondiabetic diabetes-resistant controls (P less than 0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85 +/- 0.02, also less than the controls (P less than 0.05). Protein A-gold labeling of GLUT-2 in beta-cells of day 1 diabetic rats revealed 2.17 +/- 0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.91 +/- 0.14 in controls (P less than 0.001) and 2.87 +/- 0.24 in the nondiabetic diabetes-prone rats (P less than 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes.


Assuntos
Linfócitos B/metabolismo , Diabetes Mellitus Experimental/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Animais , Linfócitos B/ultraestrutura , Imunofluorescência , Glucose/metabolismo , Glucose/farmacologia , Imuno-Histoquímica , Insulina/metabolismo , Masculino , Microscopia Eletrônica , Ratos , Ratos Endogâmicos
18.
J Clin Invest ; 90(2): 497-504, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1644920

RESUMO

The roles of insulin resistance and beta-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zucker (fa/fa) rats. All Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased beta-cell mass and basal and arginine-stimulated insulin secretion, indicating insulin resistance, but only 16% became diabetic. The insulin response to 20 mM glucose was normal in the perfused pancreas of all normoglycemic dexamethasone-treated rats but absent in every diabetic rat. Immunostainable high Km beta-cell transporter, GLUT-2, was present in approximately 100% of beta-cells of normoglycemic rats, but in only 25% of beta cells of diabetic rats. GLUT-2 mRNA was not reduced. All Zucker (fa/fa) rats treated with 0.2-0.4 mg/kg per d of dexamethasone for 24 d became diabetic and glucose-stimulated insulin secretion was absent in all. High Km glucose transport in islets was 50% below nondiabetic controls. Only 25% of beta cells of diabetic rats were GLUT-2-positive compared with approximately 100% in controls. Total pancreatic GLUT-2 mRNA was increased twofold suggesting a posttranscriptional abnormality. We conclude that dexamethasone induces insulin resistance, whether or not it induces hyperglycemia. Whenever hyperglycemia is present, GLUT-2-positive beta cells are reduced, high Km glucose transport into beta cells is attenuated and the insulin response to glucose is absent.


Assuntos
Dexametasona/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Resistência à Insulina , Ilhotas Pancreáticas/fisiopatologia , Animais , Transporte Biológico/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Imunofluorescência , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Insulina/genética , Insulina/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , RNA Mensageiro/genética , Ratos , Taxa Secretória/efeitos dos fármacos
19.
AJNR Am J Neuroradiol ; 28(4): 737-42, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17416831

RESUMO

BACKGROUND AND PURPOSE: Cerebral hyperperfusion syndrome is a rare but serious complication of carotid revascularization, including carotid endarterectomy (CEA) and carotid stent placement, which can occur in patients with preoperative impairments in cerebral hemodynamics. The purpose of this study was to determine whether preoperative cerebral blood volume (CBV) measured by perfusion-weighted MR imaging (PWI) could identify patients at risk for cerebral hyperperfusion after CEA. MATERIALS AND METHODS: CBV was measured by using PWI before CEA in 70 patients with unilateral internal carotid artery (ICA) stenosis (>or=70%) and without contralateral ICA steno-occlusive disease. Cerebral blood flow (CBF) was also measured by using single-photon emission CT before and immediately after CEA and on the 3rd postoperative day. RESULTS: A significant correlation was observed between preoperative CBV and increases in CBF immediately after CEA (r = 0.785, P < .0001). Whereas hyperperfusion immediately after CEA (CBF increase of >or=100% compared with preoperative values) was observed in 7 of 15 patients (47%) with elevated preoperative CBV, no patients with normal preoperative CBV exhibited post-CEA hyperperfusion. Furthermore, elevated preoperative CBV was the only significant independent predictor of post-CEA hyperperfusion. Finally, hyperperfusion syndrome developed on the 5th postoperative day in 2 of the 7 patients who displayed hyperperfusion immediately after CEA. CONCLUSION: Measurements of preoperative CBV by PWI might help to identify patients at risk for cerebral hyperperfusion after CEA in the absence of contralateral ICA steno-occlusive disease.


Assuntos
Volume Sanguíneo , Estenose das Carótidas/cirurgia , Circulação Cerebrovascular , Endarterectomia das Carótidas/efeitos adversos , Angiografia por Ressonância Magnética , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Encéfalo/irrigação sanguínea , Artéria Carótida Interna , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Neuroscience ; 143(1): 265-72, 2006 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-16949215

RESUMO

Cannabinoid receptor agonists have been demonstrated to inhibit medullary and spinal cord dorsal horn nociceptive neurons. The effect of cannabinoids on thermoreceptive specific neurons in the spinal or medullary dorsal horn remains unknown. In the present study, single-unit recordings from the rat medullary dorsal horn were performed to examine the effect of a cannabinoid receptor agonists on cold-specific lamina I spinothalamic tract neurons. The cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (WIN-2), was locally applied to the medullary dorsal horn and the neuronal activity evoked by cooling the receptive field was recorded. WIN-2 (1 microg/microl and 2 microg/microl) significantly attenuated cold-evoked activity. Co-administration of the CB1 receptor antagonist SR 141716 with WIN-2 did not affect cold-evoked activity. These results demonstrate a potential mechanism by which cannabinoids produce hypothermia, and also suggest that cannabinoids may affect non-noxious thermal discrimination.


Assuntos
Agonistas de Receptores de Canabinoides , Morfolinas/farmacologia , Naftalenos/farmacologia , Inibição Neural/efeitos dos fármacos , Células do Corno Posterior/efeitos dos fármacos , Medula Espinal/citologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Análise de Variância , Animais , Benzoxazinas , Antagonistas de Receptores de Canabinoides , Temperatura Baixa , Relação Dose-Resposta a Droga , Interações Medicamentosas , Estimulação Elétrica/métodos , Masculino , Inibição Neural/fisiologia , Inibição Neural/efeitos da radiação , Piperidinas/farmacologia , Células do Corno Posterior/fisiologia , Células do Corno Posterior/efeitos da radiação , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Rimonabanto
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