Assuntos
Autoanticorpos , Doença Enxerto-Hospedeiro , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Idoso , Autoantígenos/imunologia , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Laminina/imunologia , Masculino , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/diagnóstico , Colágeno Tipo XVIIRESUMO
Bartter syndrome (BS) is a disorder with normotensive hypokalemic alkalosis and hyperreninemic hyperaldosteronemia. BS affects infants or early childhood. Patients with BS type 3 harbor mutation in CLCNKB, Cl channel Kb. Gitelman syndrome (GS) is a disorder in childhood, with mutation in SLC12A3. Isolated adrenocorticotropin deficiency (IAD) causes secondary adrenal insufficiency. Neither elderly cases, nor cases with IAD were previously reported in BS. A 72-year-old man was admitted with acute adrenal crisis. He had been treated for IAD for 19 years. He had no trouble during perinatal period, delivery, and growth. After the recovery from adrenal crisis, laboratory tests revealed hypokalemia; 3.0 mEq/L (normal: 3.5-4.5), impaired renal function: eGFR; 37.6 mL/min/1.73 m2, normomagnesemia; 2.1 mg/dL (1.7-2.3), hyperreninemia; 59.4 ng/mL/h (0.2-2.7), hyperaldosteronemia; 23.5 ng/dL (3.0-15.9), and normal urinary ratio of calcium/creatinine. In diuretic tests, he showed a fine response to furosemide, and a mild response to thiazide. In genetic tests, no mutation of SLC12A3 was found and homozygous mutation: c.1830 G > A in CLCNKB was shown. Thus he was diagnosed as BS type 3. Current case presented with unusual features as BS type 3, 1) his late and mild clinical manifestation suggested GS rather than BS, 2) laboratory data and diuretics tests did not show typical features as BS, and 3) IAD and chronic renal failure altered electrolyte metabolism. In conclusion, current case implies that BS type 3 should be considered even in elderly cases with normotensive hypokalemia, and highlights importance of endocrinological and genetic examinations.
Assuntos
Hormônio Adrenocorticotrópico/deficiência , Síndrome de Bartter/complicações , Doenças do Sistema Endócrino/complicações , Doenças Genéticas Inatas/complicações , Hipoglicemia/complicações , Idoso , Síndrome de Bartter/diagnóstico , Síndrome de Gitelman/diagnóstico , Humanos , Hipopotassemia/diagnóstico , MasculinoRESUMO
OBJECTIVE: Ghrelin is a stomach-derived hormone. Acylation of ghrelin has been essential for its biological activities such as stimulating appetite. On the other hand, the function of des-acyl ghrelin (Des-G) has not been fully elucidated. The aim of the present study is to examine the anti-apoptotic effect of Des-G on endothelial cells. MATERIALS/METHODS: After human retinal microvascular endothelial cells (RMECs) were pretreated with or without 100nmol/L Des-G, apoptosis was induced with 0.1mmol/L hydrogen peroxide (H2O2). For pharmacological inhibition of surtuin 1 (SIRT1) catalytic activity, the cells were treated with 10µmol/L Ex-527. Inhibition of SIRT1 with siRNA was also performed. The quantitative estimation of DNA fragmentation was used as a marker of apoptosis. Furthermore, total SIRT activity in nuclear extracts, mRNA and protein levels of SIRT1, manganese superoxide dismutase (MnSOD) and catalase were determined. RESULTS: Des-G pretreatment protected RMECs from oxidative stress-induced apoptosis and increased SIRTs deacetylase activity in nuclear extracts. On the other hand, both pharmacological and siRNA mediated inhibition of SIRT1 attenuated the anti-apoptotic effect of Des-G. Moreover, Des-G increased mRNA and protein levels of SIRT1 and antioxidant enzymes such as MnSOD and CAT, which are downstream targets of SIRT1. Although the treatment of Ex-527 did not alter mRNA expression levels of SIRT1, it decreased mRNA expression levels of antioxidant enzymes in the cells with Des-G pretreatment. CONCLUSIONS: Our results suggest that SIRT1 signaling pathway contributes to protective effect of Des-G against oxidative stress-induced apoptosis.
Assuntos
Apoptose , Endotélio Vascular/citologia , Grelina/fisiologia , Microvasos/citologia , Estresse Oxidativo , Transdução de Sinais , Sirtuína 1/metabolismo , Western Blotting , Catalase/metabolismo , Células Cultivadas , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Humanos , Microvasos/enzimologia , Microvasos/metabolismo , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Vasos Retinianos/citologia , Vasos Retinianos/enzimologia , Vasos Retinianos/metabolismo , Sirtuína 1/genética , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a new clinical entity that affects various organs with increased IgG4 positive plasmacytes and progressive fibrosis. While IgG4-RDs in association with Hashimoto's thyroiditis or Riedel's thyroiditis have been reported, the relationship between IgG4-RD and Graves' disease (GD) is yet unknown. To elucidate the relation of GD to IgG4-RD, serum IgG4 levels and their clinical implications in patients with GD were investigated. METHODS: In this prospective study, serum IgG4 levels were measured in 109 patients with GD and classified into two groups according to the comprehensive diagnostic criteria of IgG4-RD previously established: (i) GD with elevated-IgG4 levels (≥ 135 mg/dL), and (ii) GD with nonelevated IgG4 (<135 mg/dL). RESULTS: Seven out of 109 patients with GD (6.4%) had elevated serum IgG4 levels [mean ± standard deviation (range): 175.0 ± 44.5 (136-266) mg/dL] and elevated ratios of IgG4/IgG [12.7 ± 4.5% (7.6%-21.2%)]. The remaining patients with GD had serum IgG4 levels and IgG4/IgG ratios of 39.6 ± 27.6 (3-132) mg/dL and 3.2 ± 2.2% (0.3%-11.5%), respectively. Ages in the elevated IgG4 group were significantly higher than those of the nonelevated IgG4 group: 54.7 ± 6.2 versus 43.4 ± 15.4 years, respectively. Ultrasound examinations revealed that the elevated IgG4 group had significantly increased hypoechogenic areas in the thyroid in comparison to the nonelevated IgG4 group (low echo scoring: 1.66 ± 0.81 vs. 0.61 ± 0.89, respectively). In the correlation analysis, TSAb (rs=0.385, n=42) titers were significantly correlated with se rum IgG4 levels, while they were not significantly different between the two groups. In the elevated IgG4 group, symptoms were controllable with a small dose of antithyroidal drug (ATD; n=4), a combination treatment with ATD and L-T4 (n=1), or L-T4 administration only one year after the first visit (n=2). CONCLUSIONS: A small portion of GD patients harbored elevated serum IgG4 levels. They were older, had increased hypoechoic areas in the thyroid, and appeared to be responsive or prone to be hypothyroid after ATD treatment. Thus, the present study suggests the presence of a novel subtype of GD. Measuring serum IgG4 levels may help to distinguish this new entity and provide potential therapeutic options for GD.
Assuntos
Doença de Graves/imunologia , Imunoglobulina G/sangue , Adolescente , Adulto , Idoso , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/classificação , Doença de Graves/tratamento farmacológico , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tiroxina/uso terapêutico , Adulto JovemRESUMO
A 72-year-old man presented with bilateral eyelid swelling and redness. An orbital CT scan showed bilateral proptosis, extraocular muscle enlargement and swollen lacrimal glands, mimicking thyroid-associated orbitopathy (TAO) with Hashimoto's thyroiditis (HT). During the patient's clinical course, spontaneous remission of lung consolidation (35 × 26 mm) was seen. A diagnosis of IgG4-related disease (IgG4-RD) was made based on an elevated serum IgG4 level (1,020 mg/dL; normal, 4-108), predominance of IgG4-positive plasma cells (IgG4/IgG: 35/70 in HPF) in the lacrimal glands and typical features of Mikulicz's disease. This report provides a novel description of this unusual disease entity among HT, TAO and IgG4-RD.
Assuntos
Doenças dos Anexos/imunologia , Oftalmopatias/imunologia , Imunoglobulina G/sangue , Doenças dos Anexos/diagnóstico , Idoso , Diagnóstico Diferencial , Oftalmopatias/diagnóstico , Feminino , Oftalmopatia de Graves/diagnóstico , Doença de Hashimoto/diagnóstico , Humanos , Imunoglobulina G/metabolismo , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/patologia , Masculino , Doença de Mikulicz/diagnósticoRESUMO
Edwardsiella tarda, a member of the Enterobacteriaceae family, is found in freshwater and marine environments. Extraintestinal infections of Edwardsiella tarda have been rarely reported. We describe a 70-year-old Japanese woman suffering from autoimmune hemolytic anemia, with liver abscess caused by Edwardsiella tarda. She had a history of cholecystectomy for gallbladder stone 10 years prior to this admission. She was successfully treated with percutaneous transhepatic abscess aspiration and meropenem. This is the first report of liver abscess caused by Edwardsiella tarda in Japan.
Assuntos
Edwardsiella tarda , Infecções por Enterobacteriaceae/complicações , Infecções por Enterobacteriaceae/diagnóstico , Abscesso Hepático/diagnóstico , Abscesso Hepático/etiologia , Idoso , Feminino , HumanosRESUMO
OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Mitocondriais/genética , Condução Nervosa/genética , Polimorfismo Genético , Alelos , Animais , Neuropatias Diabéticas/fisiopatologia , Feminino , Gânglios Espinais/metabolismo , Predisposição Genética para Doença , Genótipo , Humanos , Canais Iônicos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Ratos , Ratos Long-Evans , Análise de Regressão , Proteína Desacopladora 2RESUMO
Oxidative stress has been implicated in pancreatic beta-cell damage, insulin resistance and vascular function in diabetic patients and the dysfunction of antioxidant enzymes may be associated with the pathogenesis of diabetes. Extracellular superoxide dismutase (EC-SOD) is found in the extracellular matrix of tissues and the major scavenger of superoxide radical. To investigate the role of genetic variability for the pathogenesis of type 2 diabetes, we scanned the protein coding exon and flanking introns of EC-SOD gene for mutation in Japanese type 2 diabetic patients. We identified two missense mutations, Ala40Thr (GCG-->ACG) and Arg213Gly (CGG-->GGG), and a silent mutation, Leu53Leu (CTG-->TTG). For one of these variants, the Ala40Thr polymorphism, the frequency of Thr allele and the number of subjects with Thr allele (Ala/Thr+Thr/Thr) were higher in type 2 diabetic patients (n=205) than those in non-diabetic subjects (n=220) (33.2% versus 24.1%, p=0.003 and 55.6% versus 42.7%, p=0.008, respectively). The patients with Thr allele also showed earlier age at diagnosis of diabetes (42.2+/-7.8 years versus 44.4+/-6.9 years, p=0.037) and higher prevalence of hypertension (53.5% versus 38.5%, p=0.032) than those without the allele. Insulin sensitivity, furthermore, was evaluated in 71 type 2 diabetic patients with short insulin tolerance test (SITT). The patients with Thr allele showed lower insulin sensitivity (Kitt value of SITT) than those without the allele (1.78+/-0.78%/min versus 2.33+/-1.02%/min, p=0.012), although no significant differences in other clinical and biochemical characteristics were observed between two groups. These results suggest that the genetic variant of EC-SOD gene is associated with insulin resistance and the susceptibility to type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Substituição de Aminoácidos , Sequência de Bases , Primers do DNA , Feminino , Predisposição Genética para Doença , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Reação em Cadeia da PolimeraseRESUMO
Common uncoupling protein 2 (UCP2) promoter polymorphism -866G/A is reported to be associated with its expression in adipose tissue and the risk of obesity in Caucasians. On the other hand, several studies suggested that UCP2 expression in beta-cells is an important determinant of insulin secretion. In the Japanese population, morbid obesity is very rare, and insulin secretion capacity is relatively low as compared with Caucasians. Because UCP2 would link to insulin secretion and obesity, it might explain this ethnic difference. Here, we report that the UCP2 promoter with the A allele showed higher promoter activity in the INS-1 beta-cell line. The frequency of the A allele is higher in our Japanese study than that in Caucasians. Type 2 diabetic patients with the A allele need insulin therapy earlier and showed higher frequency of insulin treatment. Moreover glucose-induced early insulin secretion is significantly lower in patients with the A allele. However, there was no difference in allele frequency between obese and lean type 2 diabetic patients. In conclusion, UCP2 promoter polymorphism -866G/A does not affect obesity in Japanese type 2 diabetic patients but affects its transcription in beta-cells and modulates glucose-induced insulin secretion and eventually insulin requirement in Japanese type 2 diabetic patients. Higher A allele frequency in the Japanese population might partly explain the ethnic difference of insulin secretion capacity.