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1.
ESMO Open ; 9(2): 102226, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458658

RESUMO

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Seguimentos , Ásia , Oncologia , Sociedades Médicas
2.
ESMO Open ; 8(6): 102071, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38016249

RESUMO

BACKGROUND: Nivolumab therapy is a standard-of-care treatment for heavily pretreated patients with advanced gastric cancer (AGC). Previous studies have reported improvement in the objective response rate to chemotherapy after nivolumab therapy for other types of cancer. This study evaluated the efficacy and safety of chemotherapy after nivolumab therapy in AGC. PATIENTS AND METHODS: We conducted a prospective, multicenter, observational study in pretreated patients with nivolumab-refractory or -intolerant AGC. Patients received irinotecan, oxaliplatin-containing regimens, or trifluridine/tipiracil. The primary endpoint was overall survival. RESULTS: A total of 199 patients were included (median age: 69 years; male: 70%; female: 30%). Median overall survival and progression-free survival were 7.5 months [95% confidence interval (CI): 6.7-9.7 months] and 2.9 months (95% CI: 2.2-3.5 months), respectively. Objective response and disease control rates were 16.8% (95% CI: 11.6% to 23.6%) and 18.9% (95% CI: 38.9% to 54.6%), respectively. A prognostic index using alkaline phosphatase and the Glasgow Prognostic Score was generated to classify patients into three risk groups (good, moderate, and poor). The hazard ratios of the moderate and poor groups to the good group were 1.88 (95% CI: 1.22-2.92) and 3.29 (95% CI: 1.92-5.63), respectively. At the initiation of chemotherapy, 42 patients had experienced immune-related adverse events due to prior nivolumab therapy. The most common grade 3-4 adverse events were neutropenia (7.5%), anemia (8.0%), and anorexia (7.5%). CONCLUSIONS: The administration of cytotoxic chemotherapy after nivolumab therapy may give rise to a synergistic antitumor effect in AGC. Further investigation is warranted to confirm these findings.


Assuntos
Nivolumabe , Neoplasias Gástricas , Humanos , Masculino , Feminino , Idoso , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Estudos Prospectivos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Prognóstico
3.
Bone Joint J ; 100-B(11): 1487-1490, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30418063

RESUMO

AIMS: The aims of this study were to evaluate the morphology of the ankle in patients with an osteochondral lesion of the talus using 3D CT, and to investigate factors that predispose to this condition. PATIENTS AND METHODS: The study involved 19 patients (19 ankles) who underwent surgery for a medial osteochondral lesion (OLT group) and a control group of 19 healthy patients (19 ankles) without ankle pathology. The mean age was significantly lower in the OLT group than in the control group (27.0 vs 38.9 years; p = 0.02). There were 13 men and six women in each group. 3D CT models of the ankle were made based on Digital Imaging and Communications in Medicine (DICOM) data. The medial malleolar articular and tibial plafond surface, and the medial and lateral surface area of the trochlea of the talus were defined. The tibial axis-medial malleolus (TMM) angle, the medial malleolar surface area and volume (MMA and MMV) and the anterior opening angle of the talus were measured. RESULTS: The mean TMM angle was significantly larger in the OLT group (34.2°, sd 4.4°) than in the control group (29.2°, sd 4.8°; p = 0.002). The mean MMA and MMV were significantly smaller in the OLT group than in the control group (219.8 mm2, sd 42.4) vs (280.5 mm2, sd 38.2), and (2119.9 mm3, sd 562.5) vs (2646.4 mm3, sd 631.4; p < 0.01 and p = 0.01, respectively). The mean anterior opening angle of the talus was significantly larger in the OLT group than in the control group (15.4°, sd 3.9°) vs (10.2°, sd 3.6°; p < 0.001). CONCLUSION: 3D CT measurements showed that, in patients with a medial osteochondral lesion of the talus, the medial malleolus opens distally, the MMA and MMV are small, and the anterior opening angle of the talus is large. This suggests that abnormal morphology of the ankle predisposes to the development of osteochondral lesions of the talus. Cite this article: Bone Joint J 2018;100-B:1487-90.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Osteocondrite Dissecante/etiologia , Tálus/diagnóstico por imagem , Adolescente , Adulto , Articulação do Tornozelo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Osteocondrite Dissecante/diagnóstico por imagem , Osteocondrite Dissecante/patologia , Osteocondrite Dissecante/cirurgia , Fatores de Risco , Tálus/patologia , Tálus/cirurgia , Tíbia/diagnóstico por imagem , Tíbia/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
4.
Int J Oral Maxillofac Surg ; 46(8): 968-976, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28385383

RESUMO

Despite complete resection of the early stage of oral tongue cancer by partial glossectomy, late cervical lymph node metastasis is frequently observed. Gene amplification of ACTN4 (protein name: actinin-4) is closely associated with the metastatic potential of various cancers. This retrospective study was performed to demonstrate the potential usefulness of ACTN4 gene amplification as a prognostic biomarker in patients with stage I/II oral tongue cancer. Fifty-four patients with stage I/II oral tongue cancer were enrolled retrospectively, in accordance with the reporting recommendations for tumour marker prognostic studies (REMARK) guidelines. The copy number of ACTN4 and the protein expression of actinin-4 were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. The overall survival time of patients with gene amplification of ACTN4 was significantly shorter than that of patients without gene amplification (P=0.0010, log-rank test). Gene amplification of ACTN4 was a significant independent risk factor for death in patients with stage I/II oral tongue cancer (hazard ratio 6.08, 95% confidence interval 1.66-22.27). Gene amplification of ACTN4 is a potential prognostic biomarker for overall survival in oral tongue cancer.


Assuntos
Actinina/genética , Amplificação de Genes , Metástase Linfática/genética , Neoplasias da Língua/genética , Idoso , Biomarcadores Tumorais/análise , Feminino , Glossectomia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgia
5.
J Dev Orig Health Dis ; 8(2): 256-260, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27995841

RESUMO

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.


Assuntos
Aterosclerose/epidemiologia , Aterosclerose/patologia , Cobre/metabolismo , Lipídeos/análise , Adulto , Aterosclerose/metabolismo , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Japão/epidemiologia , Masculino
6.
Spinal Cord ; 55(5): 447-453, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27752060

RESUMO

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To analyze the predictive factors for postoperative ambulatory recovery in paretic non-ambulatory patients with metastatic spinal cord compression (MSCC). SETTING: Japan. METHODS: Eighty-two consecutive patients (74.4% men; mean age, 66.2 years) who could not walk before surgery due to cervical or thoracic MSCC and underwent posterior decompressive surgery between 2003 and 2014 were included. Patients were divided into two groups according to ambulatory status at 6 weeks after surgery: recovery (group R) and non-recovery (group NR). To evaluate the speed of progression of motor deficits, we assessed the period from onset of neurological symptoms to gait inability (T1). RESULTS: Fifty patients (61.0%) regained the ability to walk (group R). The period of T1 demonstrated a positive correlation with probability of ambulatory recovery (P=0.00; Kendall's tau-b=0.38), and a receiver operating characteristic curve analysis showed that the cutoff value of T1 was 5 days (area under the curve=0.72; P=0.001). In multivariate analysis, <6 days of T1 was one of the independent risk factors for failing to regain ambulatory ability (odds ratio, 8.74; P=0.00). CONCLUSIONS: The speed of progression of motor deficits can independently and powerfully predict the chance of postoperative ambulatory recovery as well as previously identified predictors. Since information about the speed of progression can be obtained easily by interviewing patients or family members, even if the patient is in an urgent state, our results will be helpful in clinical decision-making.


Assuntos
Descompressão Cirúrgica , Recuperação de Função Fisiológica/fisiologia , Compressão da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/fisiopatologia , Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/cirurgia
7.
J Dev Orig Health Dis ; 7(6): 685-688, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27451916

RESUMO

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from the intestine in response to enteral feeding to stimulate insulin secretion. We investigated the relationship serum GIP and GLP-1 levels with gestational age, and insulin secretion in preterm infants. Serum GIP and GLP-1 levels were measured at birth and at 1, 2 and 4 weeks after birth in 30 infants, including 12 born before 30th week of gestation (early group) and 18 born after 30th week of gestation (late group). Blood glucose and serum insulin levels were measured, and the quantitative insulin sensitivity check index (QUICKI) was also calculated. The levels of GLP-1 at 2 and 4 weeks were significantly higher in the early group than those in the late group. The levels of GIP were not significantly different between two groups. At 4 weeks, serum insulin level was significantly higher and QUICKI was significantly lower in the early group. Furthermore, GLP-1 levels were significantly correlated with QUICKI and the serum insulin levels in all infants at 4 weeks. In preterm infants, enteral feeding to premature intestine may be associated with GLP-1 secretion. GLP-1 is also related to stimulated insulin secretion in early postnatal period.


Assuntos
Glicemia/metabolismo , Idade Gestacional , Incretinas/sangue , Recém-Nascido Prematuro/metabolismo , Adulto , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Recém-Nascido , Insulina/sangue , Resistência à Insulina , Masculino , Projetos Piloto
9.
Br J Cancer ; 113(5): 716-21, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26313663

RESUMO

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Esofágicas/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Antígenos CD , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Caderinas/metabolismo , Reparo do DNA , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
11.
J Dev Orig Health Dis ; 5(6): 459-64, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25167084

RESUMO

Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Recém-Nascido Prematuro/metabolismo , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Análise de Variância , Glicemia/metabolismo , Colesterol/sangue , Idade Gestacional , Humanos , Recém-Nascido , Insulina/sangue , Resistência à Insulina/fisiologia , Japão/epidemiologia , Metabolismo dos Lipídeos/fisiologia , Fatores de Risco
12.
Brain Dev ; 35(1): 45-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22633446

RESUMO

AIM: This study was a randomised control trial to examine the effects of sphingomyelin (SM), on the mental, motor and behavioural development of premature infants. PATIENTS AND METHODS: Randomised, double-blind controlled trial, enroling infants born with a birth weight of less than 1500 g between January 2004 and October 2007 at Juntendo University Hospital, with follow-up to 18 months. Twenty-four preterm babies were randomly assigned; 12 were assigned to a test group and fed SM-fortified milk (SM 20% of all phospholipids in milk) and 12 were assigned to a control group (SM 13% of all phospholipids in milk). We analysed the composition of the plasma phospholipids and red-cell-membrane fatty acids, after which VEP, Fagan, BSID-II, attention and memory tests were performed. RESULTS: The percentage of SM in the total phospholipids was significantly higher in the trial group than in the control group at 4, 6 and 8 weeks. The Behaviour Rating Scale of the BSID-II, the Fagan test scores, the latency of VEP, and sustained attention test scores at 18 months were all significantly better in the trial group than in the control group. CONCLUSION: This study is the first to report that nutritional intervention via administration of SM-fortified milk has a positive association with the neurobehavioural development of low-birth-weight infants. However, detailed studies on the effects of SM on longer-term development are required.


Assuntos
Encéfalo/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Alimentos Fortificados , Leite , Esfingomielinas/administração & dosagem , Animais , Atenção/efeitos dos fármacos , Método Duplo-Cego , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Inteligência/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Leite Humano , Testes Neuropsicológicos , Projetos Piloto
13.
Placenta ; 33(10): 885-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22877695

RESUMO

Galectin 4 (Gal4) is abundantly expressed in the epithelium of the gastrointestinal tract, and functional analysis has concentrated on its roles associated with polarized membrane trafficking. This study aimed to investigate the expression of Gal4 in placentation. The expression level of Gal4 was revealed to be lower in differentiated Rcho-1 cells (a model system of rat trophoblast differentiation) than in proliferative cells. In the rat placenta, immunohistochemical analysis showed that Gal4 is preferentially located in the maternal-fetal junctional zone. These results suggest that down-regulation of Gal4 may be involved in the promotion of trophoblast cell differentiation.


Assuntos
Galectina 4/biossíntese , Placentação/fisiologia , Animais , Diferenciação Celular/fisiologia , Regulação para Baixo , Feminino , Placenta/metabolismo , Gravidez , Ratos
14.
Dis Esophagus ; 24(3): E23-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21418124

RESUMO

Autoimmune blistering skin diseases, including pemphigus vulgaris, rarely involve the esophagus. We report a case of exfoliative esophagitis with pemphigus vulgaris. A sloughing esophageal cast observed by endoscopy was dissected esophageal squamous epithelium in all layers. Our case is the fifth case of pemphigus vulgaris associated with esophageal cast formation recorded in the medical literature. Prednisolone was administered, and both the pemphigus vulgaris and exfoliative esophagitis improved. Upon findings of exfoliative esophagitis by endoscopic examination, we should consider the coexistence of blistering skin diseases, including pemphigus vulgaris.


Assuntos
Esofagite/complicações , Pênfigo/complicações , Epitélio/patologia , Esofagite/patologia , Esôfago/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Pênfigo/patologia
15.
Neuroscience ; 177: 127-37, 2011 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-21195139

RESUMO

Aging is thought to impair prefrontal cortical (PFC) structure-sensitive cognitive functions and flexibility, such as working memory and reversal learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used to treat age-related neurodegenerative disorders such as Alzheimer's disease in Japan, but its pharmacological properties have not been elucidated. The present study was designed to examine whether YKS improves age-related cognitive deficits using aged rats. YKS was administered to 21-month-old rats for 3 months. The ability to learn initially a reward rule for a T-maze discrimination task (initial learning) was examined in young control (4-month-old), aged control (24-month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory and reversal learning were examined in delayed alternation and reversal discrimination T-maze tasks, respectively. Locomotor activity was also measured in new environments. Although performance accuracy in the initial learning procedure did not differ among any experimental groups, accuracy in the delayed alternation task was significantly decreased in aged rats compared to young rats. Aged rats also showed significant decreases in accuracy in the reversal discrimination task. YKS treatment significantly ameliorated the age-related decreases in accuracy in the delayed alternation and reversal discrimination tasks. The ameliorative effects of YKS on impaired delayed alternation performance were reduced by intracranial infusions of a dopamine D1 receptor antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS effects on impaired reversal learning were done by the infusions into the orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental group. Thus, YKS ameliorated age-related impairments of working memory and reversal learning, which might be mediated by a dopaminergic mechanism in the PFC structure. These investigations provide information important for the treatment of brain dysfunctions in the elderly people.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Deficiências da Aprendizagem/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Reversão de Aprendizagem/fisiologia , Animais , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Deficiências da Aprendizagem/fisiopatologia , Deficiências da Aprendizagem/psicologia , Masculino , Medicina Kampo , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Resultado do Tratamento
16.
Neuroscience ; 170(4): 1110-9, 2010 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-20736050

RESUMO

Reversal learning is a domain that involves cognitive flexibility and is defined as the ability to rapidly alter established patterns of behavior when confronted with changing circumstances. This function depends critically on the orbitofrontal cortex (OFC) in the prefrontal cortical (PFC) structure, which is among the most sensitive to the influences of aging, and impaired reversal learning is a common functional disturbance of aged brain. The present study was designed to clarify the precisely neurochemical basis of this impaired learning in rats. For this purpose, we first examined reversal learning in young (3-month-old) and aged (24-month-old) rats using a T-maze discrimination task. The ability of aged rats to learn initially a reward rule for a T-maze discrimination task was almost equal to that of young rats, suggesting that simple discrimination ability was normal in aged rats. However, the ability to learn a reversed rule in a subsequent task was markedly impaired in aged rats. In addition, aged rats had reduced dopaminergic transmission concomitant with attenuated tyrosine hydroxylase (TH) activity in the OFC. Moreover, age-related impairment of reversal learning was improved by an intra-OFC infusion of 30 ng, but not 10 ng, of the D1 receptor agonist SKF 81297. Increasing dose of SKF 81297 to 100 ng also improved the impairment, but this effect was weaker than that of 30 ng, indicating that the SKF 81297 response was an inverted "U" pattern. The maximum SKF 81297 response (30 ng) was abolished by the D1 receptor antagonist SCH 23390. Thus, age-related impairment of reversal learning was due to a D1 receptor-mediated hypodopaminergic mechanism in the OFC. This finding provides direct evidence showing the involvement of OFC dopaminergic dysfunction in the development of cognitive inflexibility during the normal aging process.


Assuntos
Envelhecimento/psicologia , Dopamina/metabolismo , Córtex Pré-Frontal/fisiologia , Reversão de Aprendizagem , Animais , Benzazepinas/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microdiálise , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores , Reversão de Aprendizagem/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo
17.
Acta Paediatr ; 99(1): 37-41, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19785636

RESUMO

AIM: We investigated the relationship between plasma insulin-like growth factor I (IGF-I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants. METHOD: Plasma IGF-I, leptin, and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 61 VLBW infants, including 31 appropriate-for-gestational-age (AGA) and 30 small-for-gestational-age (SGA) infants. RESULTS: Insulin-like growth factor I levels were the lowest at birth, but increased gradually over the first 8 weeks of life. IGF-I was positively correlated with body weight, body length and body mass index at all time points. Leptin levels did not change over the study period. Ghrelin levels were significantly lower at birth; however, there were no significant differences between the levels after 2 weeks of age. Leptin and ghrelin levels were not correlated with anthropometrical measures. IGF-I levels at birth were significantly lower in SGA than in AGA infants, but the leptin and ghrelin levels were not significantly different between the two groups. CONCLUSION: Insulin-like growth factor I is related to length and weight gain in the prenatal and the early postnatal periods in VLBW infants, but this does not appear to be the case for leptin and ghrelin.


Assuntos
Grelina/sangue , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Recém-Nascido de muito Baixo Peso/sangue , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Análise de Variância , Estatura , Feminino , Crescimento/fisiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Masculino , Estatísticas não Paramétricas , Aumento de Peso
18.
Neuroscience ; 162(4): 1192-201, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19463906

RESUMO

There is evidence of prefrontal cortex (PFC)-dependent cognitive deficits, such as working memory impairment, during the normal aging process in humans and animals. Although working memory function and the PFC dopaminergic system are thought to be closely related, the relationship between them in aged subjects remains unclear. The present study was aimed to clarify the involvement of PFC dopaminergic activity in age-related working memory impairment. For this purpose, we examined working memory in young (3-month-old) and aged (24-month-old) rats, using the T-maze delayed alternation task. As a result, delayed alternation performance was impaired in aged rats compared to young rats, indicating age-related working memory impairment. In addition, aged rats showed reduced dopaminergic transmission in the prelimbic cortical region of the PFC, concomitant with attenuated tyrosine hydroxylase activity in the PFC, but not in the ventral tegmental area and substantia nigra, which was evaluated immunohistochemically and enzymatically. Moreover, age-related working memory impairment was improved by direct stimulation of the prelimbic cortical region of the PFC with 10 or 30 ng, but not 100 ng, of a D1 receptor agonist, SKF 81297, indicating that the SKF 81297 response was an inverted "U" pattern. The maximum SKF 81297 response (30 ng) was abolished by a D1 receptor antagonist, SCH 23390. Thus, age-related working memory impairment was through reduced PFC dopaminergic transmission caused by decreased dopamine synthesis in the prefrontal termination region, but not at the site where the projections originate. This finding provides direct evidence showing the involvement of dopaminergic dysfunction in the development of PFC cognitive deficits during the normal aging process and would help to understand the aging physiology and pathology of the brain.


Assuntos
Envelhecimento/fisiologia , Dopamina/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Comportamento Espacial/fisiologia , Animais , Benzazepinas/farmacologia , Dopamina/biossíntese , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Endogâmicos F344 , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores , Transmissão Sináptica , Tirosina 3-Mono-Oxigenase/metabolismo
19.
Neuroscience ; 159(1): 259-70, 2009 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-19141312

RESUMO

Aging is thought to be a risk factor to develop vulnerability of the neuroendocrine system, including the hypothalamic-pituitary-adrenal (HPA) axis, and dysregulation of this axis characterized by dexamethasone (DEX)-mediated negative feedback resistance is sometimes observed in elderly humans and animals. However, the influence of aging on the feedback system including an involvement of the brain is not fully understood. In the present study, we examined the suppressive effects of DEX by the systemic injection or the intracranial infusion into the prefrontal cortex (PFC), hippocampus, and hypothalamus on circulating corticosterone levels, and compared between young (3-month-old) and aged (24-month-old) rats. Moreover, we examined expression levels of glucocorticoid receptors (GRs) and their translocation from the cytoplasm to the nucleus using immunohistochemical and Western immunoblot techniques in the pituitary in addition to three brain regions. When DEX was injected systemically, the suppressive response was significantly enhanced in aged rats, compared with young rats. When DEX was infused into three brain regions, the suppressive response to DEX was abolished in aged rats. The immunohistochemical analysis revealed that the number of GR positive cells in the PFC, hippocampus, and hypothalamus was decreased, but that in the pituitary was increased, in aged rats, compared with young rats. The Western immunoblot analysis confirmed these results. Thus, basal expression levels of GRs in three brain regions were decreased, but those in the pituitary were increased, in aged rats. After the injection or infusion of DEX, the translocation of GRs in three brain regions was reduced, but that in the pituitary was enhanced, in aged rats. These results suggest that aging in rats enhances the feedback ability at the systemic level, which mainly involves the pituitary, but it attenuates the ability in the brain. These mechanisms may underlie the vulnerable neuroendocrine systems associated with aging.


Assuntos
Envelhecimento/fisiologia , Encéfalo/metabolismo , Retroalimentação Fisiológica/fisiologia , Regulação da Expressão Gênica/fisiologia , Glucocorticoides/metabolismo , Fatores Etários , Análise de Variância , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Contagem de Células , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Corticosterona/sangue , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Retroalimentação Fisiológica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Radioimunoensaio/métodos , Ratos , Ratos Endogâmicos F344 , Receptores de Glucocorticoides/metabolismo
20.
J Laryngol Otol ; 122(2): 170-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18005500

RESUMO

The relationship between varicella-zoster virus and idiopathic associated laryngeal paralysis was examined in five patients, using complement fixation or enzyme immunoassay testing. In all cases, significant changes in serum levels of varicella-zoster virus antibody were observed. Videofluoroscopy was useful in assessing the severity of the dysphagia and in making an accurate diagnosis; both laryngeal elevation and weakness of pharyngeal wall contraction were also observed. In two cases in which antiviral therapy was delayed, the outcome was poor, with increased levels of varicella-zoster virus immunoglobulin M found on enzyme immunoassay. The outcome of the condition may thus depend both on the speed of antiviral therapy commencement following onset of symptoms, and on the levels of varicella-zoster virus immunoglobulin M antibody (measured by enzyme immunoassay). Our study suggests that varicella-zoster virus should be considered in the differential diagnosis of patients with idiopathic associated laryngeal paralysis, and rapid antiviral therapy should be initiated when necessary.


Assuntos
Doenças do Nervo Glossofaríngeo/virologia , Herpes Zoster/complicações , Paralisia das Pregas Vocais/virologia , Idoso , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Feminino , Doenças do Nervo Glossofaríngeo/diagnóstico , Doenças do Nervo Glossofaríngeo/tratamento farmacológico , Herpes Zoster/diagnóstico , Herpesvirus Humano 3 , Humanos , Pessoa de Meia-Idade , Fotofluorografia/métodos , Resultado do Tratamento , Paralisia das Pregas Vocais/tratamento farmacológico
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