RESUMO
AIM: Calciprotein particles (CPPs), colloidal protein-mineral nanoparticles composed of solid-phase calcium phosphate and serum protein fetuin-A found in blood, are emerging as a novel component of chronic kidney disease-mineral and bone disorder (CKD-MBD). The relationship of CPPs with factors known to underlie the CKD-MBD pathophysiology is not well known.The aim of this study is to examine daily variations in CPPs as well as their association with mineral metabolism parameters in normal individuals and early-stage CKD patients. METHODS: Twenty subjects (10 healthy adults, 10 diabetic patients) were enrolled. Serum CPP Fetuin-A was measured and analyzed in relation to clinical parameters. RESULTS: Estimated glomerular filtration rates (eGFR) were 103 ± 11 and 75 ± 24 mL/min per 1.73 m2 in healthy adults and diabetic patients, respectively. Serum CPP Fetuin-A (g/L) were elevated at postprandial 2 h in diabetic patients. Furthermore, serum CPP Fetuin-A were inversely correlated with eGFR and serum 1,25-dihydroxyvitamin D3 and magnesium levels and were positively correlated with serum fibroblast growth factor-23. CONCLUSIONS: These findings indicated that serum CPP Fetuin-A were affected by food intake and may contribute to the pathophysiology of mineral metabolism in subjects with normal and moderately impaired renal function.
Assuntos
Fosfatos de Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Nefropatias Diabéticas/sangue , Insuficiência Renal Crônica/sangue , alfa-2-Glicoproteína-HS/análise , Adulto , Idoso , Biomarcadores/sangue , Calcitriol/sangue , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Estudos Transversais , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Ingestão de Alimentos , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ligação Proteica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologiaRESUMO
There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hormônios Peptídicos/sangue , Adulto , Idoso , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Glicemia/análise , Peptídeo C/sangue , HDL-Colesterol/sangue , Jejum , Feminino , Hemoglobinas Glicadas/análise , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
BACKGROUND: The aim of the study was to evaluate the correlation between angiopoietin-like protein 8 (ANGPTL8) and metabolic parameters in non-diabetic healthy humans. METHODS: We enrolled 30 healthy Japanese adults (25 men and five women). After 9 h of fasting, we collected blood samples and analyzed the ANGPTL8, lipoprotein lipase (LPL), plasma lipid and glucose metabolic parameters. In addition, we performed 75-g oral glucose tolerance test (OGTT) and measured adipokines (tumor necrosis factor-α, leptin and adiponectin). RESULTS: Median serum ANGPTL8 level was 224 (167 - 437) pg/mL, and serum ANGPTL8 level positively correlated with serum triglyceride level (r = 0.42, P = 0.021) and negatively correlated with LPL level (r = -0.44, P = 0.015). ANGPTL8 level showed no correlation with body mass index (BMI), waist-hip ratio, and homeostasis model assessment of insulin resistance (HOMA-IR) or with adipose tissue-derived adiponectin and leptin levels. Further, ANGPTL8 showed no association with glucose and insulin levels after 75-g OGTT. CONCLUSION: Serum ANGPTL8 level negatively correlated with LPL levels in healthy Japanese adults. Regulation of ANGPTL8 could be a promising therapeutic target for hypertriglyceridemia.
RESUMO
The present study was undertaken to clarify a role of interleukin-12p40 gene (IL-12B) polymorphism, located on chromosome 5q33-34 (IDDM 18), in Japanese subjects with Type 1 diabetes mellitus (T1DM) and autoimmune thyroid diseases (AITD). In 179 subjects with T1DM, 166 with AITD (128 with Graves' disease and 38 with Hashimoto's thyroiditis) and 115 healthy control subjects, the IL-12B 3'UTR A-C polymorphism was determined by PCR-RFLP method. In T1DM subjects, the genotype was also analyzed in relation to human leukocyte antigen (HLA)-DRB1-DQB1 haplotype status. There was a weak difference in the distribution of the genotype frequency between T1DM and control subjects, and the C allele frequency was higher in T1DM subjects (P<0.05). In 68 T1DM subjects without having high-risk HLA haplotypes to T1DM in this population, the genotype distribution and C allele frequency was significantly different from control subjects without high-risk HLA haplotypes (P<0.01), and from T1DM subjects with high-risk HLA haplotypes (n=111) (P<0.05). There was no difference in the genotype and allele frequencies between AITD and control subjects. In conclusion, the IL-12B 3'UTR A-C polymorphism did not seem to play a major role on genetic susceptibility to T1DM and AITD in Japanese, although the polymorphism conferred susceptibility in T1DM subjects without having high-risk HLA haplotypes. The IL-12B 3'UTR A-C polymorphism would be considered as a supplementary risk factor to T1DM in conjunction with HLA haplotypes.
Assuntos
Cromossomos Humanos Par 3 , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA , Interleucina-12/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Idade de Início , Mapeamento Cromossômico , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Subunidade p40 da Interleucina-12 , JapãoRESUMO
BACKGROUND: Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis. In developed renal dysfunction, FGF23 levels increase to maintain the phosphate excretion capacity. However, in diabetic patients with early-stage renal impairment, the FGF23 elevation is not very sensitive. We hypothesized that urinary phosphate (U-P)/serum FGF23 ratio would theoretically be an index that reflects the number of nephrons (nephron index). In this study, we determined whether the nephron index would be associated with renal function and vascular diseases in diabetic patients. METHODS: In total, 142 patients with diabetes mellitus were enrolled. The nephron index was calculated using the following formula: U-P (mg/day)/ serum FGF23 (pg/ml). RESULTS: The mean age was 63 ± 11 years and eGFR levels were 79.5 ± 25.4 ml/min/1.73 m2, respectively. Thirty patients had a medical history of macroangiopathy. The Nephron index was significantly decreased in subjects with macroangiopathy compared with those without macroangiopathy. A multivariate analysis of risk factors for macroangiopathy revealed that duration of diabetes, eGFR, and nephron index were significantly associated with a higher frequency of arteriosclerotic disease. CONCLUSION: These findings suggest that a decrease in nephron index reflects early-stage renal impairment and is an independent risk factor of macroangiopathy in diabetic patients.
Assuntos
Aterosclerose/complicações , Fatores de Crescimento de Fibroblastos/sangue , Fosfatos/urina , Insuficiência Renal Crônica/complicações , Aterosclerose/sangue , Aterosclerose/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Previous studies have shown that glucose effectiveness and insulin sensitivity are acutely enhanced by exercise at various intensities. The aim of this study was to determine the effects of a single bout of exercise at intensities recommended by the American Diabetes Association (ADA) and the American College of Sports Medicine (ACSM) on glucose uptake-specific glucose effectiveness (S(G)(2)*) and insulin sensitivity (S(I)(2)*). S(G)(2)* and S(I)(2)* were estimated by a two-compartment minimal model. DESIGN: Six healthy men (age, 28.5 +/- 2.0 yr) performed a stable-labeled frequently sampled iv glucose tolerance test (FSIGT) under three separate conditions: without any prior exercise, and immediately after single 20-min bouts of cycle ergometer exercise at an intensity of 50% and 70% of maximal oxygen uptake (Vo(2max)). The exercise intensities were close to the lower and upper boundaries recommended by the ADA and ACSM. RESULTS: Glucose disappearance constant (K(G)), S(G)(2)*, and S(I)(2)* increased after exercise in an intensity-dependent manner. Increases in S(G)(2)* (+237.1 +/- 50.5%), S(I)(2)* (+225.6 +/- 51.9%), and K(G) (+151.7 +/- 16.5%) following exercise at 70% Vo(2max) were statistically significant (P < 0.05), whereas those at 50% Vo(2max) were not. CONCLUSIONS: In conclusion, a single bout of exercise acutely improves S(I)(2)* and S(G)(2)* in individuals with normal glucose tolerance in an intensity-dependent manner.
Assuntos
Exercício Físico , Glucose/metabolismo , Proteínas Quinases Ativadas por AMP , Adulto , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4 , Humanos , Masculino , Proteínas de Transporte de Monossacarídeos/metabolismo , Complexos Multienzimáticos/metabolismo , Proteínas Musculares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
For examining the effects of moderate exercise training on peripheral glucose effectiveness (S(g)(2)*), insulin sensitivity (S(i)(2)*), and endogenous glucose production (EGP), seven men and one woman (24.8 +/- 1.8 years) participated in cycle ergometer training at lactate threshold intensity for 60 min/day, 5 days/week for 12 weeks. Stable-labeled frequently sampled intravenous glucose tolerance tests were performed before and 16 h and 1 week after the last training session. S(g)(2)* (pre 0.71 +/- 0.03 x 10(-2), 16 h 0.85 +/- 0.02 x 10(-2) dl. kg(-1). min(-1)) and S(i)(2)* (pre 12.6 +/- 2.6 x 10(-4), 16 h 19.7 +/- 3.3 x 10(-4) dl. kg(-1). min(-1). [ micro U/ml](-1)), analyzed using the two-compartment minimal model, were significantly elevated 16 h after the last training session. The elevated S(g)(2)* remained higher despite the cessation of exercise training for 1 week (1.00 +/- 0.03 x 10(-2) dl. kg(-1). min(-1)). EGP was suppressed within 20 min after glucose bolus, and the suppression of EGP was followed by their overshoot. The time course of EGP during the intravenous glucose tolerance test remained similar after the training period. In conclusion, moderate exercise training at lactate threshold improves not only peripheral insulin sensitivity but also peripheral glucose effectiveness with no change in the effect of glucose and/or insulin to suppress EGP in healthy humans.
Assuntos
Glucose/metabolismo , Insulina/farmacologia , Aptidão Física/fisiologia , Adulto , Glicemia/metabolismo , Peso Corporal , Ácidos Graxos não Esterificados/sangue , Feminino , Gluconeogênese , Teste de Tolerância a Glucose , Humanos , Lactatos/metabolismo , Masculino , Modelos Biológicos , Valores de ReferênciaRESUMO
In order to develop an intracisternal penicillin rat model of epilepsy, eleven anesthetized male Wistar rats were studied. 5 underwent intracisternal injection of penicillin (doses 150,000-300,000 units) in the prone position, and another 5 underwent intraperitoneal penicillin injection; one died following intracisternal injection, prior to further study. Time between penicillin injection and seizure induction (determined by electroencephalography) was recorded. Each animal had a tracheostomy, and was mechanically ventilated and carefully monitored for adverse effects. Seizures were noted in an average of 13:42 minutes following penicillin injection (range 4:30-23:20) for the intracisternally (IC) injected group. Both episodic and continuous seizure activity was seen, and a dose-dependent effect was seen (quicker-onset, more continuous seizures with higher doses, in the IC group). Onset was significantly faster in the IC than for the intraperitoneally injected group (all >1 hour for the latter group in our study). 96 total separate seizure episodes were seen, ranging from 3 to 540 seconds. Epileptic activity could be seen in all IC-injected rats lasting over 1 hour into the study. The intracisternal penicillin injection rat model appears to provide a quick-onset, reliable method of inducing seizure activity in the rat model while leaving the cranial vault intact.
Assuntos
Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Penicilinas , Animais , Injeções Intraperitoneais , Masculino , Ratos , Ratos WistarRESUMO
Electroconvulsive therapy (ECT) effect upon seizure cessation was studied in five male Wistar rats using a penicillin intracisternal injection model (which did not damage the cranial vault). Animals were observed both clinically and electrographically for seizure development. ECT was applied at varying times following onset of seizure, at varying parameters (frequency, pulsewidth, and duration). ECT affected EEG seizure pattern in several different stimulation parameter-dependent ways: (1) modulation to different pattern; (2) increased interictal time; and (3) seizure cessation. Stimulation with higher, sustained current (50 mA) led to changes in seizure amplitude; stimulation at pulses of current led to seizure frequency dimunition, and at certain characteristic pulses "capture" was seen as the EEG activity mimicked the ECT-inducing stimulation pattern. Interictal time was usually increased by sustained, continuous (rather than pulsatile) stimulation. Seizure activity was completely stopped in several instances using parameters of 800 pulses at a frequency of 200 Hz, with 2.56 ms pulsewidth and 50 mA of current (in consecutive iterations for one specimen). No ECT-related adverse effects were noted. Analogous to the heart, pacing or defibrillating the brain using external scalp electrodes may have a role in the control of otherwise intractable seizures.
Assuntos
Modelos Animais de Doenças , Eletroconvulsoterapia , Convulsões/terapia , Idade de Início , Animais , Masculino , Penicilinas , Ratos , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
A 73-year-old woman was admitted due to weight loss and generalized malaise. The basal levels of all the anterior pituitary hormones, except for prolactin, were reduced. However, they were all elevated in response to exogenous hypothalamic hormones. After starting hydrocortisone replacement, the patient had polyuria of >5,000 mL/day. T1-weighted MRI depicted a low signal of an oval mass in the sella turcica and an iso-intense signal of another mass at the pituitary stalk. These findings indicate a hypothalamic type of hypopituitarism and masked central diabetes insipidus which possibly derived from the atypical occupation of Rathke's cleft cyst at the pituitary stalk.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cistos do Sistema Nervoso Central/patologia , Diabetes Insípido Neurogênico/patologia , Hidrocortisona/uso terapêutico , Hipopituitarismo/patologia , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/patologia , Idoso , Cistos do Sistema Nervoso Central/complicações , Diabetes Insípido Neurogênico/etiologia , Feminino , Humanos , Hipopituitarismo/etiologia , Neoplasias Hipofisárias/complicaçõesRESUMO
The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.
Assuntos
Apoptose , Isquemia Encefálica/terapia , Encéfalo/patologia , Oxigenoterapia Hiperbárica , Oxigênio/metabolismo , Animais , Encéfalo/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Caspases/metabolismo , Corantes/metabolismo , Fragmentação do DNA , Modelos Animais de Doenças , Marcação In Situ das Extremidades Cortadas , Infarto da Artéria Cerebral Média , Masculino , Testes Neuropsicológicos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sais de Tetrazólio/metabolismoRESUMO
OBJECTIVE: Hyponatremia occurs not infrequently in hypopituitarism. Arginine vasopressin (AVP)-induced impaired water excretion is found in patients with hypopituitarism and experimental models of glucocorticoid deficiency. DESIGN: The present study was undertaken to determine whether augmented release of AVP is involved in the development of hyponatremia in elderly subjects with secondary adrenal insufficiency. METHODS: Forty patients with ACTH-deficient, secondary adrenal insufficiency were examined. They were divided into three groups according to the age at which diagnosis was ascertained (group A <20 Years, group B 20-64 Years, and group C>or=65 Years). RESULTS: Hyponatremia was more manifest in the elderly group than in the other two groups, serum sodium (Na) levels being 124.7 mmol/l in the elderly group, a value significantly less than 141.5 and 133.5 mmol/l in groups A and B. Plasma AVP levels seemed likely to be high compared with the respective hypo-osmolality in plasma in the elderly group, as plasma AVP levels were 1.7 pmol/l despite a mean plasma osmolality of 259 mmol/kg. Such an alteration was less clear in group B and was not found in group A. Therefore, elevation of plasma AVP was apparent in the elderly patients. Hydrocortisone replacement promptly normalized serum Na levels from 125 to 142 mmol/l (P<0.01) and reduced plasma AVP levels from 1.7 to 0.9 pmol/l (P<0.05), which were comparable to the respective plasma osmolality in the elderly patients. CONCLUSION: These results indicate that non-suppressible release of AVP is crucially involved in the impaired water excretion and hyponatremia seen in elderly patients with secondary adrenal insufficiency compared with the younger patients, and that exaggerated release of AVP becomes manifest as the subjects grow older.
Assuntos
Insuficiência Adrenal/complicações , Insuficiência Adrenal/metabolismo , Envelhecimento/metabolismo , Arginina Vasopressina/metabolismo , Hiponatremia/etiologia , Adolescente , Insuficiência Adrenal/tratamento farmacológico , Hormônio Adrenocorticotrópico/deficiência , Adulto , Idoso , Hormônios/sangue , Humanos , Hidrocortisona/uso terapêuticoRESUMO
Insulin-sensitizing thiazolidinediones (TZDs) decrease inflammatory markers such as high-sensitive C-reactive protein (hsCRP) in sera in addition to their hypoglycemic effects. However, factors associated with the decrease in serum hsCRP concentrations are unclear. In the present study, an effect of troglitazone on serum hsCRP levels was investigated and compared with its effect on glycemia. A total of 34 subjects with type 2 diabetes (17 men and 17 women, aged 54+/-2 years and body mass index (BMI) 26.7+/-0.6 kg/m(2), mean+/-S.E.) were studied. Nineteen out of the 34 subjects was treated with troglitazone 400mg daily for 12 weeks. The remaining 15 subjects were treated with metformin 750 mg daily as a control group. Baseline hsCRP levels were comparable between the two groups, and those were positively associated with fasting insulin levels. After treatment, glycemic control assessed by HbA1c and fasting glucose levels improved in both groups, whereas insulin sensitivity index estimated by homeostasis model assessment (HOMA-R) decreased only in the troglitazone-treated group. Serum levels of hsCRP significantly decreased from 916+/-210 ng/ml to 569+/-123 ng/ml (P<0.05) in the troglitazone-treated group, whereas the levels remained unchanged in the metformin-treated group (from 1087+/-248 ng/ml to 1152+/-301 ng/ml). In the troglitazone-treated group, there was no difference in the absolute and percent change in serum hsCRP levels between responders, who displayed the decrease in HbA1c greater than 0.6% (n=12), and the remaining non-responders (n=7). The decrease in serum hsCRP concentrations was negatively related to baseline levels of serum hsCRP and insulin and HOMA-R. In conclusion, troglitazone, but not metformin, reduced serum hsCRP levels in type 2 diabetic patients. The decrease in serum hsCRP concentrations by troglitazone was associated with the pretreatment levels of hsCRP and insulin resistance, but independent of the changes in glycemia.
Assuntos
Glicemia/análise , Proteína C-Reativa/metabolismo , Cromanos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Tiazolidinedionas/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fatores de Tempo , TroglitazonaRESUMO
OBJECT: Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm. METHODS: An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2-treated, and Src inhibitor damnacanthal-treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal. CONCLUSIONS: The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.
Assuntos
Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/enzimologia , Vasoespasmo Intracraniano/etiologia , Quinases da Família src/metabolismo , Animais , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Western Blotting , Angiografia Cerebral , Modelos Animais de Doenças , Cães , Feminino , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de Tempo , Vasoespasmo Intracraniano/tratamento farmacológico , Quinases da Família src/antagonistas & inibidoresRESUMO
RhoA, a member of the Rho small G protein family, mediates multiple intracellular signaling pathways, and is highly expressed in renal cortex. RhoA translocation is associated with RhoA activation. This study was undertaken to examine the relation of translocation of RhoA in the renal cortex with diabetic renal injury in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups and were studied at 8 weeks after STZ-injection (55 mg/kg, i.v). We found that the kidney weight and urinary protein excretion were significantly increased in diabetic rats. Diabetic glomerulopathy was confirmed by mesangial matrix expanding and glomerular basement membrane thickening. The ratio of membrane-bound RhoA verses cytosolic RhoA is 1.8 fold higher (p < 0.01) in diabetic group, indicating an enhanced RhoA translocation. There was no significant difference in total RhoA protein expression and RhoA mRNA expression between diabetic and control groups. These data suggest that RhoA translocation might be involved in diabetic renal injury.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Córtex Renal/metabolismo , Transporte Proteico/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Peso Corporal , Fracionamento Celular , Córtex Renal/citologia , Córtex Renal/patologia , Masculino , Tamanho do Órgão , Proteinúria/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína rhoA de Ligação ao GTP/genéticaRESUMO
Thiazide diuretics are known to produce severe hyponatremia as well as hypokalemia. The present study demonstrated severe hyponatremia in three hypertensive patients who had received combination therapy consisting of an angiotensin II receptor blocker (ARB) and thiazide. The serum sodium (Na) levels in all three cases were markedly reduced to below 116 mmol/L, and the patients exhibited augmented urinary excretion of Na with a reduced circulatory blood volume. After withdrawing the ARB and thiazide treatment, the serum Na levels normalized within one to two weeks. Combination therapy with ARBs and thiazide may cause hyponatremia in elderly patients.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Hipertensão/tratamento farmacológico , Hiponatremia/induzido quimicamente , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Humanos , Hipertensão/fisiopatologia , Hiponatremia/sangue , Masculino , Índice de Gravidade de Doença , Sódio/sangue , Sódio/urina , Inibidores de Simportadores de Cloreto de Sódio/uso terapêuticoRESUMO
A 78-year-old man with abdominal pain was diagnosed with a rupture of a gastric artery aneurysm. The serum Na level promptly decreased from 135 to 110 mmol/L within several days. Brain magnetic resonance angiography revealed severe vasoconstriction of the cerebral basilar artery and anterior cerebral artery. There was neither dehydration nor edema. The plasma arginine vasopressin level was 3.3 pg/mL, despite hypoosmolality. These findings indicated a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) derived from severe vasoconstriction of the cerebral arteries. The administration of 7.5 mg of tolvaptan rapidly increased the serum Na level from 123 to 138 mmol/L within the first 24 hours, thereafter continuously maintaining a normal level. Treatment with tolvaptan corrected the patient's dilutional hyponatremia.
Assuntos
Aneurisma/complicações , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Benzazepinas/uso terapêutico , Hiponatremia/tratamento farmacológico , Hiponatremia/etiologia , Síndrome de Secreção Inadequada de HAD/complicações , Dor Abdominal , Idoso , Arginina Vasopressina , Encéfalo/irrigação sanguínea , Humanos , Síndrome de Secreção Inadequada de HAD/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Concentração Osmolar , Estômago/irrigação sanguínea , TolvaptanRESUMO
Aim of this study was to formulate an index for glucose effectiveness (Sg), SgIo, based on 3-point (0, 30 and 120 min) 75 g oral glucose tolerance test (OGTT). The equation for SgI(O) was developed in the Chikuma cohort (n = 502). Firstly, post-loading plasma glucose without insulin action and Sg (PPG-without insulin and Sg) was calculated as follows: fasting plasma glucose (mg/dl) + [0.75 × 75,000]/[0.19 × BW(kg) × 10]. Secondly, 'PPG-without insulin/with Sg' was obtained from inverse correlation between log(10)DI(O) and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DI(O) denotes oral disposition index, a product of the Matsuda Index and δIRI(0-30)/δPG(0-30). Thirdly, expected 2hPG (2hPG(E)) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPG(E) (2hPG/2hPG(E)) was determined as an adjustment factor. Lastly, SgI(O) ([mg/dl]/min) was calculated as [PPG-without insulin and Sg]-[PPG-without insulin / with Sg] x [(2hPG) / 2hPG(E)]. SgI(O) was validated against Sg obtained by frequently sampled intravenous glucose tolerance test in the Jichi cohort (n = 205). Also, the accuracy of prediction of Sg by SgIo was tested by the Bland-Altman plot. SgI(O) was 3.61 ± 0.73, 3.17 ± 0.74 and 2.15 ± 0.60 in subjects with normal glucose tolerance (NGT), non-diabetic hyperglycemia and diabetes, respectively, in the Chikuma cohort. In the Jichi cohort, SgI(O) was significantly correlated with Sg in the entire group (r = 0.322, P < 0.001) and in subjects with NGT (r = 0.286, P < 0.001), and SgIo accurately predicted Sg. In conclusion, SgI(O) could be a simple, quantitative index for Sg.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Teste de Tolerância a Glucose/métodos , Glucose/metabolismo , Adulto , Idoso , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose/normas , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Glucose dynamics measured in ambulatory settings are fluid in nature and exhibit substantial complexity. We recently showed that a long-range negative correlation of glucose dynamics, which is considered to reflect blood glucose controllability over a substantial period, is absent in patients with diabetes mellitus. This was demonstrated using detrended fluctuation analysis (DFA), a modified random-walk analysis method for the detection of long-range correlations. In the present study, we further assessed the relationships between the established clinical indices of glycemic or insulinogenic control of hemoglobin A(1c) (HbA(1c)), glycated albumin (GA), 1,5-anhydroglucitol, and urine C-peptide immunoreactivity and the recently proposed DFA-based indices obtained from continuous glucose monitoring in 104 Japanese diabetic patients. Significant correlations between the following parameters were observed: (1) HbA(1c) and the long-range scaling exponent α(2) (r = 0.236, P < .05), (2) GA and α(2) (r = 0.254, P < .05), (3) GA and the short-range scaling exponent α(1) (r = 0.233, P < .05), and (4) urine C-peptide immunoreactivity and the mean glucose fluctuations (r = -0.294, P < .01). Therefore, we concluded that increases in the long-range DFA scaling exponent, which are indicative of the lack of a long-range negative correlation in glucose dynamics, reflected abnormalities in average glycemic control as clinically determined using HbA(1c) and GA parameters.