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OBJECTIVE: to investigate whether harmine has a promotive effect on human periodontal ligament cells (hPDLCs)-induced tissue regeneration. MATERIALS AND METHODS: Various concentrations of harmine on hPDLCs proliferation were tested. Osteogenic and cementogenic characteristics were examined in hPDLC/rhBMP-2 and hPDLC/harmine by alizarin red S staining, real-time PCR, and Western blotting assay. The activity of harmine was investigated in an ectopic transplantation nude mouse model. RESULTS: We determined that 10 µM of harmine was the threshold concentration. hPDLC/harmine showed similar mineralized nodule formation in alizarin S staining compared to hPDLC/rhBMP-2. In real-time PCR, the highest gene expression level was observed for Runx2 in hPDLC/harmine at all time points. The level of CEMP-1 in hPDLC/harmine was higher at 7 days than hPDLCs alone. Thicker band of Runx2 in hPDLC/harmine was observed than in hPDLC/rhBMP-2 at 7 days by Western blotting. The band for CEMP-1 in hPDLC/harmine was thicker than hPDLCs alone at both 7 and 14 days. In ectopic transplantation, hPDLCs with harmine showed a comparable amount of mineralized tissue formation compared to rhBMP-2. hPDLCs with harmine or rhBMP-2 formed both bone and cementum-like tissue with Sharpey's fiber-like collagen insertion. CONCLUSION: Harmine can be a potential candidate for promoting hPDLCs-induced tissue regeneration.
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Proteína Morfogenética Óssea 2/farmacologia , Proliferação de Células/efeitos dos fármacos , Harmina/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Ligamento Periodontal/citologia , Regeneração/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Camundongos Nus , Osteocalcina/genética , Osteocalcina/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteínas Recombinantes/farmacologia , Transplante HeterólogoRESUMO
OBJECTIVES: Metabolically obese but normal weight (MONW) individuals constitute a subgroup of normal weight individuals that display impaired insulin sensitivity with a higher risk of developing diabetes, cardiovascular disease and mortality. We aimed to propose a novel criterion for defining MONW by examining the usefulness and the cutoff value of the TyG index, a product of the levels of triglycerides and glucose, in identifying MONW individuals. In addition, the performance of this criterion in predicting the future incidence of diabetes was assessed. SUBJECTS/METHODS: A total of 7541 non-diabetic, normal weight (body mass index ⩾18.5 and <25 kg m(-)(2)) subjects were selected from the Korea National Health and Nutrition Examination Survey conducted in 2009-2010. Another 3185 participants with follow-up studies were selected from a prospective community-based cohort study. The TyG index was calculated as ln(fasting triglycerides (mg dl(-1)) × fasting glucose (mg dl(-1))/2). RESULTS: The levels of the TyG index paralleled the prevalence of metabolic syndrome and its components. The cutoff value of the TyG index that reflected MONW based on the receiver operating characteristics analysis was 8.82 for men and 8.73 for women, with the area under the curve values being 0.855 and 0.868, respectively. The sensitivity and the specificity were 84.2 and 77.6% in men and 69.1 and 89.4% in women, respectively. Individuals designated as MONW, who have a normal weight and TyG levels higher than cutoff, displayed a metabolically unhealthy phenotype and an approximately twofold higher risk of developing diabetes compared with metabolically healthy normal weight subjects. CONCLUSIONS: We propose a simple diagnostic criterion of MONW, which might be used to discriminate subjects with a higher risk of metabolic diseases.
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The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were -0.78 % and -1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pirazóis/uso terapêutico , Tiazolidinas/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada/métodos , Jejum , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , República da Coreia/etnologiaRESUMO
AIM: As serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. METHODS: A total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8 mg/L. Subclinical atherosclerosis was defined as a carotid artery intima-media thickness (C-IMT) ≥ 0.9 mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30 mg/g creatinine). RESULTS: Patients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02-3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11-4.72) per 1mg/L increase of B2M. CONCLUSION: Higher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.
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Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Microglobulina beta-2/sangue , Adulto , Idoso , Aterosclerose/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de RiscoRESUMO
AIMS: Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea. METHODS: Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. RESULTS: The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. CONCLUSION: There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.
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Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/epidemiologia , Pacientes Internados , Doenças do Sistema Nervoso Periférico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
AIMS: This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy. METHODS: An open, randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain-intensity score > or = 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36-item Short Form Health Survey, average pain intensity and sleep disturbance. RESULTS: One hundred and sixty-three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 +/- 1.6; gabapentin 6.3 +/- 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A -3.1 +/- 2.0; gabapentin -2.7 +/- 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores. CONCLUSION: This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
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Acetaminofen/administração & dosagem , Aminas/administração & dosagem , Analgésicos Opioides/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Tramadol/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Resultado do TratamentoRESUMO
AIMS: We investigated whether cardiovascular autonomic neuropathy (CAN) is associated with acute ischaemic stroke in patients with Type 2 diabetes. METHODS: From 1999 to 2000, cardiovascular autonomic function tests were conducted in patients with Type 2 diabetes (n = 1458). Patients were followed up between 2006 and 2007. Standard tests for CAN measured heart rate variability parameters [expiration-to-inspiration (E/I) ratio, responses to the Valsalva manoeuvre and standing]. Using the American Diabetes Association criteria, the CAN scores were determined from the results of each test as follows: 0 = normal, 1 = abnormal (total maximum score 3). We assessed the development of acute ischaemic stroke events. RESULTS: The prevalence of CAN at baseline was 55.7% (E/I 17.1%, Valsalva 39.4%, posture 27.3%) (n = 1126). During follow-up, 131 patients (11.6%) developed acute ischaemic stroke. The vascular events were more frequent in older patients (P < 0.001) and in those with diabetes of longer duration (P = 0.022), hypertension (P < 0.001) or diabetic retinopathy (P = 0.03) than in patients without vascular events. Patients with ischaemic stroke had higher creatinine levels (P = 0.045) and higher urine albumin excretion (P = 0.025) than those of patients without stroke. Cox proportional hazard regression analysis revealed that the CAN score was associated with the development of acute ischaemic stroke (total score 0 vs. 3, adjusted hazard ratio 2.7, 95% CI 1.3-5.5, P = 0.006). CONCLUSION: Cardiovascular autonomic dysfunction was significantly associated with the development of ischaemic stroke in patients with Type 2 diabetes.
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Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Acidente Vascular Cerebral/complicações , Fatores Etários , Idoso , Albuminúria/complicações , Biomarcadores/urina , Creatinina/urina , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/urina , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Hipertensão/fisiopatologia , Hipertensão/urina , Incidência , Masculino , Pessoa de Meia-Idade , Postura , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/urina , Fatores de Tempo , Manobra de ValsalvaRESUMO
Oncocytoma is a neoplasm that can arise in several organs, and it has been more commonly described in the kidney, salivary gland and thyroid. Oncocytoma arising in the adrenal gland is a rare finding. Moreover, functioning adrenocortical oncocytoma is exceptionally rare. A 47-yr-old man was incidentally discovered to have a right adrenal mass. The patient had no clinical features suggestive of increased adrenal function. However, hormonal evaluation showed a disturbed cortisol circadian rhythm, supranormal urinary cortisol excretion, a low level of ACTH, and a lack of suppressibility of cortisol secretion after dexamethasone. Right adrenalectomy was performed, and this revealed a well-circumscribed dark-brown tumor that measured 2.4x2.2 cm. The tumor consisted almost exclusively of large eosinophilic and epitheloid cells whose cytoplasm was packed with eosinophilic granulations, which corresponded to the numerous mitochondria confirmed on electron microscopy. This is a rare case of subclinical Cushing's syndrome that was caused by adrenocortical oncocytoma.
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Adenoma Oxífilo/patologia , Neoplasias do Córtex Suprarrenal/patologia , Síndrome de Cushing/patologia , Adenoma Oxífilo/cirurgia , Adenoma Oxífilo/ultraestrutura , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/ultraestrutura , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/cirurgia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Humanos , Inibinas/metabolismo , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Sinaptofisina/metabolismoRESUMO
Hyperparathyroidism may be a precipitating factor important to the development of myelofibrosis: however, there has been only a few reports regarding myelofibrosis secondary to primary hyperparathyroidism. Recently, a rare case of pancytopenia caused by myelofibrosis in a 41-year-old woman who complained of general weakness and arthralgia presented to our clinical service. The patient was diagnosed with primary hyperparathyroidism with pancytopenia. Bone marrow biopsy revealed myelofibrosis. Right parathyroidectomy was performed and a parathyroid adenoma was totally excised. After surgery, the CBC counts and other clinical abnormalities gradually improved without further intervention. We concluded that the pancytopenia was because of bone marrow fibrosis resulting from primary hyperparathyroidism. Therefore, physicians should consider myelofibrosis secondary to primary hyperparathyroidism as a cause of pancytopenia in hypercalcemic patients, even though it is rare.
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Hiperparatireoidismo/complicações , Pancitopenia/etiologia , Neoplasias das Paratireoides/complicações , Mielofibrose Primária/etiologia , Adulto , Feminino , Humanos , Hiperparatireoidismo/patologia , Hiperparatireoidismo/cirurgia , Pancitopenia/patologia , Pancitopenia/cirurgia , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Mielofibrose Primária/patologia , Mielofibrose Primária/cirurgiaRESUMO
AIMS: Patient education is a very important part of diabetes care. However, until now, little data has been presented about the long-term effectiveness of structured intensive diabetes education programmes (SIDEP) for people with Type 2 diabetes mellitus. METHODS: People with Type 2 diabetes (n = 547) hospitalized from December 1999 to December 2000 were randomly assigned to two groups. Two hundred and nineteen patients undertook an inpatient SIDEP and the remaining patients received conventional glycaemic control without intensive education. After discharge, all patients were monitored regularly. Laboratory data were obtained, and adherence to self-care behaviour was determined on a five-point scale by questionnaires completed annually. RESULTS: Of the patients who completed the SIDEP, 160 (73.1%) were followed up for more than 4 years. The mean HbA(1c) (7.9 +/- 1.2 vs. 8.7 +/- 1.6%; P < 0.05) and the frequency of hospitalization related to diabetes per patient per year (0.3 +/- 0.6 vs. 0.8 +/- 0.9; P < 0.05) was significantly lower in the SIDEP group than in the control group. The SIDEP group adhered more closely to self-care behaviour than the control group over 4 years (P < 0.05). People with Type 2 diabetes mellitus of longer duration and those treated with insulin had poorer HbA(1c) at follow-up. CONCLUSIONS: A well-designed, intensive patient education programme is necessary for people with diabetes. However, regular and sustained reinforcement with encouragement is also required to maintain optimal glycaemic control, especially in insulin-treated patients.
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Diabetes Mellitus Tipo 2/terapia , Educação de Pacientes como Assunto/métodos , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado/tendências , TempoRESUMO
OBJECTIVES: This study was performed to investigate the effect of dexamethasone on the expansion and transdifferentiation of transplanted neonatal pancreas cell clusters (NPCCs) in vivo. METHODS: Porcine NPCCs were generated from 1 to 3-day-old neonatal pigs. After transplantation (Tx) of 4000 islet equivalents (IEqs) of NPCCs beneath the renal subcapsular space of normoglycemic nude mice, dexamethasone (Dx, 1 mg/kg) or vehicles were injected daily. Intraperitoneal glucose tolerance testing (ip-GTT) was performed at 4 weeks (n = 4) and 10 weeks (n = 7) after Tx. After harvesting the grafts, total graft and beta-cell graft mass were determined by morphometric analysis. RESULTS: Although the mean value of AUCg was elevated in the Dx-treated group at 10 weeks after Tx, the glucose levels of all the animals by ip-GTT were within the normal range. At 10 weeks after Tx, the relative volume, absolute mass of beta-cells in the graft, and total graft mass were significantly lower in the Dx-treated group (relative volume of beta-cells: 22.0% versus 35.3%, P < 0.05; beta-cells mass: 1.0 +/- 1.2 mg versus 2.2 +/- 5.6 mg, P < 0.05, total graft mass: 4.4 +/- 5.4 mg versus 6.3 +/- 1.3 mg, P < 0.05, Dx-treated versus control), but there was no difference at 4 weeks. Morphologically prominent cystic structures were observed in the Dx group at 10 weeks. CONCLUSION: Our results suggest that dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine NPCCs into beta-cells in normal nude mice.
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Diferenciação Celular/efeitos dos fármacos , Dexametasona/farmacologia , Transplante das Ilhotas Pancreáticas/fisiologia , Transplante Heterólogo/fisiologia , Animais , Animais Recém-Nascidos , Divisão Celular/efeitos dos fármacos , Teste de Tolerância a Glucose , Insulina/metabolismo , Secreção de Insulina , Camundongos , Camundongos Nus , Ensaio de Cápsula Sub-Renal , SuínosRESUMO
OBJECTIVES: The expression of the intermediate filament (IF) vimentin, usually considered a marker of mesenchymal cells, has been observed in the epithelial cells during embryogenesis, carcinogenesis, and dedifferentiation, suggesting that it might be useful as a marker of proliferating precursor cells in the pancreas. METHODS: Rat pancreata at E18 and at different time points after partial pancreatectomy (Px) and human and neonatal pig pancreatic tissue sections and monolayer cultured pancreatic duct cells were observed. All tissues were simultaneously immunostained with pancytokeratin and vimentin antibodies. In costained duct cells, PDX-1 or PCNA expression was also analyzed using confocal microscope images. RESULTS: In the rat embryonic pancreas at E18, all epithelial cells that formed ductlike structures expressed both cytokeratin and vimentin IF, whereas no duct cells costained for IF in the adult rat or neonatal pig pancreas. Such costaining reappeared in the following order: common pancreatic duct, main ducts, foci of regeneration and then disappeared completely at 30 days after Px. In humans, costaining was found in only 1 diabetic patient's pancreatic section, which was accompanied by massive duct cell proliferation. In monolayer culture, most of the duct cells of human and neonatal pigs coexpressed both IF proteins. Only a few costained duct cells also expressed PDX-1, and most of those cells were also stained with PCNA in rat embryonic pancreas and regenerating foci after partial Px. CONCLUSIONS: Vimentin IF expression might be a useful marker for pancreatic precursor cells and could be used to investigate the concept of the dedifferentiation of fully matured duct cells during the process of the beta-cell neogenesis.
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Pâncreas/citologia , Ductos Pancreáticos/citologia , Células-Tronco/metabolismo , Vimentina/metabolismo , Animais , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Humanos , Pâncreas/embriologia , Pâncreas/crescimento & desenvolvimento , Pancreatectomia , Ductos Pancreáticos/crescimento & desenvolvimento , Ductos Pancreáticos/metabolismo , Ratos , Células-Tronco/citologia , SuínosRESUMO
Osteoporosis is a common disease among patients undergoing transplantation and a loss of bone mass is usually detected after bone marrow transplantation (BMT), particularly during the immediate post-BMT period. Post-BMT bone loss is primarily related to gonadal dysfunction and immunosuppression. Cytokines, especially interleukin 6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study was to assess the relationship between bone turnover markers and cytokines, which are regularly sampled at peripheral blood and bone marrow before and after allogeneic BMT. This prospective study included two analyses. The first was a study of 46 BMT recipients (M/F 28/18), examining the relationship between bone turnover markers and serum cytokines that were measured before and at 1 week, 2 weeks, 3 weeks, 4 weeks and 3 months after BMT. Serum intact parathyroid hormone was measured before BMT and at 3 weeks after BMT and its relation to other cytokines and bone turnover markers was evaluated. The second analysis was a study of 14 (M/F 9/5) of 46 patients in whom bone marrow plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)] were measured at 3 weeks after BMT. The relationship between bone marrow plasma cytokines and bone turnover markers was studied because bone marrow is the microenvironment where the real changes in bone turnover occur. Serum type I collagen carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, a bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. Serum IL-6 increased until 2 weeks after BMT and declined thereafter. Serum TNF-alpha increased until 3 weeks after BMT and declined thereafter. There was a significant positive correlation between serum ICTP and bone marrow IL-6 levels at 3 weeks after BMT, when a marked change in bone metabolism occurs following BMT. However, a correlation between bone turnover markers and bone marrow TNF-alpha or peripheral blood cytokines was not found. At 3 months after BMT, there was a significant negative correlation between the mean daily steroid dose and the serum osteocalcin level (r = -0.43, p < 0.05). The correlation between the Mean daily steroid dose and serum ICTP was also significant (r = 0.41, p < 0.05). Our data suggest that the progressive increase in bone resorption during the immediate post-BMT period is related to both steroid dose and the increase in bone marrow IL-6, which is a potent stimulator of bone resorption in vivo.
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Transplante de Medula Óssea/efeitos adversos , Remodelação Óssea/fisiologia , Citocinas/fisiologia , Osteoporose/etiologia , Adulto , Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Interleucina-6/sangue , Interleucina-6/fisiologia , Masculino , Osteoporose/fisiopatologia , Prednisolona/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
BACKGROUND: It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. RESULTS: In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. CONCLUSION: These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina , Tetrazóis/farmacologia , Vasodilatadores/farmacologia , Animais , Animais Recém-Nascidos , Cilostazol , Diabetes Mellitus Tipo 2/induzido quimicamente , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Masculino , Probabilidade , Ratos , Ratos Wistar , Valores de Referência , Sensibilidade e Especificidade , EstreptozocinaRESUMO
Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.
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Arginina Vasopressina/metabolismo , Hipernatremia/etiologia , Neoplasias Hipotalâmicas/metabolismo , Sede , Adulto , Humanos , Masculino , Concentração OsmolarRESUMO
Autoimmune diseases can be transmitted and eliminated by bone marrow transplantation (BMT). There have been several cases of autoimmune thyroid disease (AITD) occurring after BMT, but AITD remission has been rarely reported. We present four cases in which the remission or transfer of AITD occurred after an allogeneic BMT. Two patients with severe aplastic anemia (SAA) showed evidence of remission of Hashimoto's thyroiditis which they had before allogeneic BMT. One patient with SAA, which developed during treatment with propylthiouracil for Graves' disease, underwent allogeneic BMT and showed evidence of Graves' disease remission following BMT. In one patient, new AITD occurred after an allogeneic BMT from an HLA-matched sibling who already had AITD. These cases support the evidence that the immune system is newly reconstituted after BMT, and severe autoimmune disease can be an indication for BMT. To fully understand the real changes in autoimmune status after BMT, long-term prospective studies are necessary.
Assuntos
Doenças Autoimunes/terapia , Transplante de Medula Óssea/efeitos adversos , Doenças da Glândula Tireoide/terapia , Adolescente , Adulto , Anemia Aplástica/terapia , Doenças Autoimunes/etiologia , Feminino , Doença de Graves/terapia , Histocompatibilidade , Humanos , Masculino , Doenças da Glândula Tireoide/etiologia , Tireoidite Autoimune/etiologia , Tireoidite Autoimune/terapia , Transplante Homólogo/imunologiaRESUMO
Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.
Assuntos
Transplante de Medula Óssea , Osso e Ossos/metabolismo , Minerais/metabolismo , Adolescente , Adulto , Biomarcadores , Densidade Óssea , Feminino , Doenças Hematológicas/metabolismo , Doenças Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The aim of this study was to compare the shaping ability of three ProFile rotary instrumentation techniques and a conventional step-back method in simulated root canals. Prevalence of canal aberrations, change in working length, and preparation time were measured. A total of 48 composite images were made from pre- and postcanal scanned images using Corel Photopaint 8.0 and then the amount of coronal substance the instruments removed was also calculated two-dimensionally on digitized images with the Brain C software to compare the enlarging efficiency. There were no significant differences between the three rotary groups in preparation time, change in working length, and the incidence of aberrations (p > 0.05). The amount of coronal substance the instruments removed in the ProFile .04 taper group was significantly smaller than the other three groups (p < 0.05).
Assuntos
Carbono , Cavidade Pulpar/anatomia & histologia , Modelos Anatômicos , Preparo de Canal Radicular/instrumentação , Distribuição de Qui-Quadrado , Corantes , Ligas Dentárias , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador/métodos , Incidência , Teste de Materiais , Níquel , Prevalência , Pulpectomia/instrumentação , Resinas Sintéticas , Preparo de Canal Radicular/métodos , Rotação , Software , Aço Inoxidável , Estatísticas não Paramétricas , Propriedades de Superfície , Fatores de Tempo , Titânio , Coroa do DenteRESUMO
BACKGROUND: To compare the 1997 American Diabetes Association (ADA) criteria with the 1985 World Health Organization (WHO) criteria in categorization of the diabetes diagnostic status of Koreans and to define clinical characteristics of subjects diagnosed differently by the two criteria. METHODS: In 810 Korean subjects, we analyzed blood glucose and insulin response during 75 g oral glucose tolerance test (OGTT). According to current WHO criteria, the cutoff values of FPG which distinguish normal and IGT from diabetes were determined. Then the subjects were categorized according to both WHO and ADA criteria. The clinical characteristics of the subjects with different diagnostic categories by the two criteria were defined. RESULTS: The FPG cut point distinguishing diabetes from IGT was 117 mg/dl, and from normal was 110 mg/dl. The overall agreement between the ADA criteria and the WHO criteria was moderate, as reflected in the kappa of 0.45. 141 of subjects categorized diabetes by WHO criteria were not diagnosed with ADA criteria. These discordant subjects were older in age and showed blunted early insulin response than concordant normal subjects. CONCLUSION: These results suggest that mild diabetes by the WHO criteria, especially in the elderly, would not be diagnosed as diabetes by the ADA FPG criteria only. Thus, in a group at high risk for developing diabetes or in a relatively older age group, we should continue using the OGTT.