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1.
J Endocrinol Invest ; 40(1): 49-54, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27507082

RESUMO

PURPOSE: The aim of the present study was to evaluate the role of hypothyroidism as a cause of hyponatremia in a clinical model of iatrogenic acute hypothyroidism due to thyroid hormone withdrawal prior to ablative radioactive iodine (RAI) therapy after total thyroidectomy. METHODS: The study group consisted of 101 differentiated thyroid cancer (DTC) patients (77 women and 24 men). Plasma concentration of thyroid-stimulating hormone ([TSH]) and sodium ([Na+]) was evaluated before total thyroidectomy (pre[TSH] and pre[Na+]) and on the day of RAI therapy (post[TSH] and post[Na+]). RESULTS: The frequency of hypothyroidism-associated hyponatremia was 4 % (4/101). Pre[Na+] was significantly higher than post[Na+] (140.7 ± 1.6 vs 138.7 ± 2.3 mEq/L, p = 0.012). Moreover, a linear correlation was identified between pre[Na+] and post[Na+]. CONCLUSIONS: Iatrogenic acute hypothyroidism-related hyponatremia is uncommon. However, because of the significant reduction of [Na+] in the transition from euthyroidism to iatrogenic hypothyroidism, the value of pre[Na+] should be viewed as a parameter to be considered. Since it acts as an independent risk factor for the development of hyponatremia, patients with a pre[Na+] close to the lower limit of normal range may deserve a closer monitoring of [Na+].


Assuntos
Hiponatremia/radioterapia , Hipotireoidismo/radioterapia , Radioisótopos do Iodo/uso terapêutico , Complicações Pós-Operatórias/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Doença Aguda , Feminino , Humanos , Hiponatremia/etiologia , Hipotireoidismo/etiologia , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações
2.
Clin Biochem ; 49(1-2): 85-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26232286

RESUMO

OBJECTIVES: The recent guideline for the evaluation and management of Chronic Kidney Disease recommends assessing GFR employing equations based on serum creatinine; despite this, creatinine clearance 24-hour urine collection is used routinely in many settings. In this study we compared the classification assessed from CrCl (creatinine clearance 24h urine collection) and e-GFR calculated with CKD-EPI or MDRD formulas. DESIGN AND METHODS: In this retrospective study we analyze consecutive laboratory data: creatinine clearance 24h urine collection, serum creatinine and demographic data such as sex and age from 15,777 patients >18 years of age collected from 2011 to 2013 in our laboratory at Careggi Hospital. The results were then compared to the estimated GFR calculated with the equations according to the recent treatment guidelines. Consecutive and retrospective laboratory data (creatinine clearance 24h urine collection, serum creatinine and, demographic data such as sex and age) from 15,777 patients >18 years of age seen at Careggi Hospital were collected. RESULTS: Comparison between e-GFR calculated with CKD-EPI or MDRD formulas and GFR according CrCl determinations and bias [95% CI] were 11.34 [-47,4/70.1] and 11.4 [-50.2/73] respectively. The concordance for 18/65 years aged group when compared with e-GFR classification between MDRD vs CKDEPI, MDRD vs CrCl and CKD-EPI vs CrCl were 0.78, 0.34, and 0.41 respectively, while in the 65/110years aged group the concordance Kappas were 0.84, 0.38, and 0.36 respectively. CONCLUSIONS: The use of CrCl provides a different classification than the estimation of GFR using a prediction equation. The CrCl is unreliable when it is necessary to identify CKD subjects with decrease of GFR of 5ml/min/1.73m(2)/year.


Assuntos
Creatinina/urina , Falência Renal Crônica/classificação , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/urina , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
J Clin Endocrinol Metab ; 93(3): 876-80, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18089696

RESUMO

OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.


Assuntos
Diabetes Gestacional/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , Gravidez
5.
J Endocrinol Invest ; 30(11): 925-30, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18250613

RESUMO

BACKGROUND: The adoption of the International Diabetes Federation (IDF) criteria for metabolic syndrome (MS), in comparison with the National Cholesterol Educational Program (NCEP) criteria, produces different changes in estimates of prevalence in diverse populations. Few data are available in Caucasian non-diabetic subjects. PATIENTS AND METHODS: The prevalence of NCEP- and IDF-defined MS was assessed in a sample of 2,945 individuals, aged 55.2+/-11.5 yr, enrolled in a screening program for diabetes. Association of different definitions of MS with glucose intolerance (120-min glucose 7.8 mmol/l after a 75 g-oral glucose load) and hyperuricemia (>0.38 mmol/l) was also assessed. RESULTS: The prevalence of MS was 16.6% and 29.7% with NCEP and IDF definitions, respectively. The prevalence of NCEP-defined MS was higher than IDF-MS through all age ranges; among those aged >60 yr, the prevalence of IDF-MS reached 52.8% (vs 33.1% for NCEP-MS). Both NCEP- and IDF-MS were associated with glucose intolerance and hyperuricemia. Individuals fulfilling IDF, but not NCEP criteria for MS, showed a prevalence of glucose intolerance (22.7%) significantly (p<0.05) lower than those fulfilling NCEP criteria only (31.6%) or both sets of criteria (31.8%). CONCLUSION: In Caucasian subjects without known diabetes, IDF criteria produce a relevant increase in estimates of prevalence of MS, particularly in older subjects, when compared with NCEP criteria. NCEP-MS seems to be more effective than IDF-MS in the identification of glucose intolerant subjects.


Assuntos
Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Programas Nacionais de Saúde , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diagnóstico Diferencial , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Itália/epidemiologia , Masculino , Programas de Rastreamento , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Prevalência , Relação Cintura-Quadril
6.
Diabetologia ; 48(6): 1168-72, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15864535

RESUMO

AIMS/HYPOTHESES: Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP-IV) activity in endothelial cells in vitro. The present study was designed to assess the effect of high glucose on circulating DPP-IV activity in patients with type 1 and type 2 diabetes. METHODS: Plasma DPP-IV activity was measured in 29 patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects. We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA1c > 8.5% and in plasma from matched groups of 31 newly diagnosed diabetic subjects with HbA1c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample of 66 type 2 diabetic patients, a longitudinal study was also performed to evaluate variations in DPP-IV activity and HbA1c over 3 months. RESULTS: DPP-IV activity in type 1 diabetic patients was not significantly different from that in control subjects; however, a significant correlation between DPP-IV and HbA1c was observed in diabetic subjects (r = 0.47; p < 0.01). Type 2 diabetic patients with HbA1c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean+/-SD 27.7+/-7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT (22.1+/-6.0 and 18.8+/-8.8 U/l, respectively). Variations in DPP-IV activity over 3 months in type 2 diabetic patients showed a significant positive correlation with variations in HbA1c (r = 0.26; p < 0.05). CONCLUSIONS/INTERPRETATION: Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type 1 and type 2 diabetes. This phenomenon could contribute to the reduction in circulating active glucagon-like peptide-1 and to the consequent postprandial hyperglycaemia in type 2 diabetic patients with poor metabolic control.


Assuntos
Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/sangue , Hiperglicemia/metabolismo , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hiperglicemia/sangue , Estudos Longitudinais , Masculino , Valores de Referência , Análise de Regressão
7.
J Med Genet ; 42(3): 214-20, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15744034

RESUMO

BACKGROUND: Skeletal muscle disorders associated with mutations of lamin A/C gene include autosomal Emery-Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B. The pathogenic mechanism underlying these diseases is unknown. Recent data suggest an impairment of signalling mechanisms as a possible cause of muscle malfunction. A molecular complex in muscle cells formed by lamin A/C, emerin, and nuclear actin has been identified. The stability of this protein complex appears to be related to phosphorylation mechanisms. OBJECTIVE: To analyse lamin A/C phosphorylation in control and laminopathic muscle cells. METHODS: Lamin A/C N-terminal phosphorylation was determined in cultured mouse myoblasts using a specific antibody. Insulin treatment of serum starved myoblast cultures was carried out to evaluate involvement of insulin signalling in the phosphorylation pathway. Screening of four Emery-Dreifuss and one limb girdle muscular dystrophy 1B cases was undertaken to investigate lamin A/C phosphorylation in both cultured myoblasts and mature muscle fibres. RESULTS: Phosphorylation of lamin A was observed during myoblast differentiation or proliferation, along with reduced lamin A/C phosphorylation in quiescent myoblasts. Lamin A N-terminus phosphorylation was induced by an insulin stimulus, which conversely did not affect lamin C phosphorylation. Lamin A/C was also hyperphosphorylated in mature muscle, mostly in regenerating fibres. Lamin A/C phosphorylation was strikingly reduced in laminopathic myoblasts and muscle fibres, while it was preserved in interstitial fibroblasts. CONCLUSIONS: Altered lamin A/C interplay with a muscle specific phosphorylation partner might be involved in the pathogenic mechanism of Emery-Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B.


Assuntos
Lamina Tipo A/metabolismo , Distrofia Muscular de Emery-Dreifuss/metabolismo , Mioblastos/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Diferenciação Celular , Linhagem Celular , Humanos , Insulina/metabolismo , Lamina Tipo A/genética , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular de Emery-Dreifuss/genética , Fosforilação , Transdução de Sinais
8.
Diabetes Nutr Metab ; 17(6): 336-42, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15887627

RESUMO

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Glucagon/sangue , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Obesidade/sangue , Obesidade/complicações , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Adulto , Idoso , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Jejum , Feminino , Peptídeo 1 Semelhante ao Glucagon , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade
9.
Eur J Histochem ; 47(1): 3-16, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12685553

RESUMO

The present review summarizes recent cytochemical findings on the functional organization of the nuclear domains, with a particular emphasis on the relation between nuclear envelope-associated proteins and chromatin. Mutations in two nuclear envelope-associated proteins, emerin and lamin A/C cause the Emery-Dreifuss muscular dystrophy; the cellular pathology associated with the disease and the functional role of emerin and lamin A/C in muscle cells are not well established. On the other hand, a large body of evidence indicates that nuclear envelope-associated proteins are involved in tissue-specific gene regulation. Moreover, chromatin remodeling complexes trigger gene expression by utilizing the nuclear matrix-associated actin, which is known to interact with both emerin and lamin A/C. It is thus conceivable that altered expression of these nuclear envelope-associated proteins can account for an impairment of gene expression mainly during cell differentiation as suggested by recent experimental findings on the involvement of emerin in myogenesis. The possibility that Emery-Deifuss muscular dystrophy pathogenesis could involve alteration of the signaling pathway is considered.


Assuntos
Imuno-Histoquímica , Distrofia Muscular de Emery-Dreifuss/metabolismo , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Membrana Nuclear/metabolismo , Expressão Gênica , Humanos , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Distrofia Muscular de Emery-Dreifuss/genética , Membrana Nuclear/genética , Proteínas Nucleares , Transdução de Sinais , Timopoietinas/genética , Timopoietinas/metabolismo
10.
Acta Diabetol ; 40(4): 181-6, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14740278

RESUMO

The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG > or =7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA1C is effective in the screening of IGT; although combined FPG and HbA1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/diagnóstico , Jejum , Intolerância à Glucose/diagnóstico , Hemoglobinas Glicadas/análise , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , França/epidemiologia , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Obesidade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Caracteres Sexuais
11.
Neuromuscul Disord ; 12(9): 815-23, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12398831

RESUMO

Elucidation of the pathophysiology of Emery-Dreifuss muscular dystrophy, caused by mutations in emerin or lamin A/C, will require deciphering the role of these proteins in the functional organization of the nuclear envelope. This review focuses on nuclear envelope related mechanisms that modulate chromatin arrangement and control of gene transcription, both potential targets of the disease process in Emery-Dreifuss muscular dystrophy. Interactions of these proteins with chromatin- and nuclear matrix-associated proteins are now of particular interest, since chromatin alterations occur in cells in Emery-Dreifuss muscular dystrophy. Both emerin and lamin A/C interact with nuclear actin, a component of the chromatin remodeling complex associated with the nuclear matrix, suggesting that either chromatin arrangement, or gene transcription, or both, might be impaired in the disease.


Assuntos
Núcleo Celular/fisiologia , Cromatina/genética , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Animais , Núcleo Celular/metabolismo , Expressão Gênica , Humanos , Proteínas de Membrana/genética , Distrofia Muscular de Emery-Dreifuss/genética , Distrofia Muscular de Emery-Dreifuss/metabolismo , Membrana Nuclear/metabolismo , Membrana Nuclear/fisiologia , Matriz Nuclear/metabolismo , Matriz Nuclear/fisiologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transcrição Gênica , Cromossomo X
12.
Minerva Chir ; 57(1): 59-62, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11832860

RESUMO

BACKGROUND: Procalcitonin (PCT) is a new marker for severe infection that is supposed to have a useful role in the early detection of bacterial infection in the perioperative period. AIM OF THE STUDY: to test the hypothesis that PCT is useful as an early marker of postoperative infectious complications. METHODS: Thirty-three patients were submitted to major abdominal interventions that comprehend an intestinal resection (mean age: 49.9+/-19.3 years; 19 males, 14 females). PCT was tested at 4 times: T1=preoperative; T2=6 hours after starting interventions; T3=24 hours after; T4=48 hours after. STATISTICAL: "t"-Student test and Pearson correlation. RESULTS: In the postoperative course 11 patients had infectious complications that were: 3 wound infections, 2 positive haemocolture, 1 pneumonia, 3 deep abdominal infections, 2 anastomotic dehiscences. In these patients only the 24 hours PCT assay at T3 was higher than in the other patients that had not complications (microgram/ml 4.74+/-3.8 vs 1.22+/-0.8; p<0.0001). The cut off value of 1 ng/ml has a sensibility of 70% and a specificity of 81%. CONCLUSIONS: PCT detection appear to be an important aid for early diagnosis of postoperative infectious complications when it is used with the other indexes.


Assuntos
Infecções Bacterianas/sangue , Calcitonina/sangue , Complicações Pós-Operatórias/sangue , Precursores de Proteínas/sangue , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo
13.
FEBS Lett ; 509(3): 423-9, 2001 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-11749967

RESUMO

Emerin is a nuclear membrane-anchored protein which is absent or mutated in patients affected by Emery-Dreifuss muscular dystrophy. In this study, we induced apoptosis in cultured mouse myoblasts to evaluate emerin fate during the nuclear destabilization involved in programmed cell death. Emerin proteolysis was observed in myocytes during the apoptotic process. Myoblast apoptosis and emerin degradation were associated with chromatin compaction and detachment from the nuclear lamina, as detected by electron microscopy. In vivo specific inhibition of caspase 3 or caspase 6 activity completely abolished emerin proteolysis. These results show that the process of programmed cell death in muscle cells leads to emerin proteolysis, which appears to be related to caspase 6 activation and to cleavage of other nuclear envelope proteins, that share sequence homologies or functional features with emerin.


Assuntos
Caspases/metabolismo , Proteínas de Membrana/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estaurosporina/farmacologia , Timopoietinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Inibidores de Caspase , Linhagem Celular , Meios de Cultura Livres de Soro , Cinética , Camundongos , Microscopia Eletrônica , Microscopia de Fluorescência , Músculos/enzimologia , Músculos/ultraestrutura , Proteínas Nucleares , Fatores de Tempo
14.
Matrix Biol ; 20(7): 475-86, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11691587

RESUMO

Fibronectin is one of the main components of the extracellular matrix and associates with a variety of other matrix molecules including collagens. We demonstrate that the absence of secreted type VI collagen in cultured primary fibroblasts affects the arrangement of fibronectin in the extracellular matrix. We observed a fine network of collagen VI filaments and fibronectin fibrils in the extracellular matrix of normal murine and human fibroblasts. The two microfibrillar systems did not colocalize, but were interconnected at some discrete sites which could be revealed by immunoelectron microscopy. Direct interaction between collagen VI and fibronectin was also demonstrated by far western assay. When primary fibroblasts from Col6a1 null mutant mice were cultured, collagen VI was not detected in the extracellular matrix and a different pattern of fibronectin organization was observed, with fibrils running parallel to the long axis of the cells. Similarly, an abnormal fibronectin deposition was observed in fibroblasts from a patient affected by Bethlem myopathy, where collagen VI secretion was drastically reduced. The same pattern was also observed in normal fibroblasts after in vivo perturbation of collagen VI-fibronectin interaction with the 3C4 anti-collagen VI monoclonal antibody. Competition experiments with soluble peptides indicated that the organization of fibronectin in the extracellular matrix was impaired by added soluble collagen VI, but not by its triple helical (pepsin-resistant) fragments. These results indicate that collagen VI mediates the three-dimensional organization of fibronectin in the extracellular matrix of cultured fibroblasts.


Assuntos
Colágeno Tipo VI/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células Cultivadas , Colágeno Tipo VI/genética , Fibroblastos/citologia , Humanos , Camundongos , Camundongos Knockout , Camundongos Nus
15.
Clin Chem Lab Med ; 39(9): 801-5, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11601676

RESUMO

Pregnancy-induced hypertensive disorders (PIHD) are common complications of pregnancy and are associated with increased maternal and fetal morbidity. In this study, artificial neural networks (aNN) and multivariate logistic regression (MLR) were applied to a set of clinical and laboratory data (urea, creatinine, uric acid, total proteins, hematocrit, iron and ferritin) collected at 16 and 20 weeks of gestation. The efficacy of the two approaches in predicting the development of PIHD in 303 consecutive normotensive pregnant women at high risk of pre-eclampsia and intrauterine fetal growth retardation was then compared. The aNN were trained with a randomly selected set of 187 patient records and evaluated on the remainder (n=116). MLR analysis was done with the same 116 patients. The performance of each model was assessed using receiver operator characteristic (ROC) curves. Pregnancies had a normal physiological course in 227 cases, whereas 76 (25.1%) women developed PIHD during the third trimester. The best aNN at 20 weeks yielded an area under the ROC curve of 0.952, the sensitivity of 86.2%, the specificity of 95.4%, the positive predictive value of 86.2% and the negative predictive value of 95.5% for PIHD. The corresponding values for the MLR at 20 weeks were 0.962, 79.3%, 97.7%, 92% and 93.4%, respectively. The computer-aided integrated use of these conventional tests seems to provide a useful means for and early prediction of PIHD development.


Assuntos
Hipertensão/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Aborto Habitual , Adolescente , Adulto , Área Sob a Curva , Feminino , Morte Fetal , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Estudos Longitudinais , Pessoa de Meia-Idade , Redes Neurais de Computação , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Gravidez , Curva ROC , Fatores de Risco
16.
Muscle Nerve ; 24(6): 826-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11360268

RESUMO

Electron microscopy study of muscle biopsies from patients with autosomal-dominant Emery-Dreifuss muscular dystrophy revealed nuclear alterations in about 10% of the preserved muscle fibers. The major findings consisted of peripheral heterochromatin loss or detachment from the nuclear envelope, and of interchromatin texture alterations. These abnormalities are similar to those reported in an animal model of the disease and to those found in the X-linked form of Emery-Dreifuss muscular dystrophy. These results suggest that an abnormal ultrastructural arrangement of the nuclear periphery is a common feature in the known forms of Emery-Dreifuss muscular dystrophy, and that several proteins of the nuclear scaffold are necessary in muscle cells to maintain the nuclear structural/functional integrity and a normal muscle cell metabolism.


Assuntos
Núcleo Celular/patologia , Músculo Esquelético/patologia , Distrofia Muscular de Emery-Dreifuss/genética , Distrofia Muscular de Emery-Dreifuss/patologia , Adulto , Substituição de Aminoácidos , Biópsia , Núcleo Celular/ultraestrutura , Criança , Feminino , Heterocromatina/patologia , Heterocromatina/ultraestrutura , Humanos , Laminas , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/ultraestrutura , Proteínas Nucleares/genética , Cromossomo X
17.
Diabetes Care ; 24(3): 489-94, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11289473

RESUMO

OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS: A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7-36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS: Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.


Assuntos
Leptina/sangue , Metformina/uso terapêutico , Obesidade/sangue , Obesidade/tratamento farmacológico , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Adolescente , Adulto , Glicemia/metabolismo , Glucagon , Peptídeo 1 Semelhante ao Glucagon , Peptídeos Semelhantes ao Glucagon , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade
18.
Ital Heart J ; 2(3): 222-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11305534

RESUMO

BACKGROUND: The role of cardiac troponin I (cTnI) is well established in acute myocardial ischemia. However, its role in myocardial contusion remains to be clarified. Since transesophageal echocardiography (TEE) appears, at present, to be the best method for the diagnosis of myocardial contusion, the aim of this study was to measure the concentration of cTnI in patients with blunt chest trauma studied using TEE. METHODS: Thirty-two patients (27 males, 5 females, mean age 44+/-20 years), admitted to the Trauma Center of our Institution with clinical and/or radiological signs of acute blunt chest trauma, underwent biplane TEE within 24 hours of injury; serial blood samples were taken to measure cTnI levels (normal values < 0.4 ng/ml), using fluorimetric enzyme immunoassay. RESULTS: Abnormal levels of cTnI were found in 17 patients (53%): 7 patients had levels of cTnI between 0.4 and 1 ng/ml, whereas 10 patients had levels > 1 ng/ml. Segmental wall motion abnormalities consistent with myocardial contusion could be identified by echocardiography in 6/10 patients with cTnI levels > 1 ng/ml (60%) but in no patients with normal cTnI levels or with titers between 0.4 and 1 ng/ml; mean cTnI levels showed a significant difference between the two groups of patients with and without echocardiographic signs of myocardial contusion (2.6+/-1.6 vs 0.6+/-1.4 ng/ml, p < 0.001). CONCLUSIONS: Abnormal titers of cTnI suggesting myocardial contusion may be found in more than half of patients with blunt chest trauma; however, myocardial injury can be detected by TEE only for cTnI levels > 1 ng/ml; cTnI concentrations ranging between 0.4 and 1 ng/ml might be indicative of myocardial microlesions, not detectable by echocardiography, even if TEE is used; cTnI assay could therefore be suggested as a screening test before performing TEE after blunt chest trauma.


Assuntos
Ecocardiografia Transesofagiana/métodos , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/diagnóstico por imagem , Troponina I/análise , Ferimentos não Penetrantes/sangue , Ferimentos não Penetrantes/diagnóstico por imagem , Adulto , Biomarcadores/análise , Feminino , Humanos , Escala de Gravidade do Ferimento , Itália , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Sensibilidade e Especificidade , Centros de Traumatologia
20.
Diabet Med ; 17(10): 713-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11110504

RESUMO

AIMS: To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus. METHODS: Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7-36)amide and GLP-1(7-37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp. RESULTS: GLP-1(7-36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7-53.2) vs. 128.7(100-172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)amide and GLP-1(7-37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7-36)amide at 30, 60, and 90 min, and GLP-1(7-37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load. DISCUSSION: Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus/sangue , Glucagon/sangue , Leptina/sangue , Obesidade/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Peptídeo 1 Semelhante ao Glucagon , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Hiperinsulinismo , Insulina/administração & dosagem , Insulina/sangue , Insulina/farmacologia , Masculino , Pessoa de Meia-Idade
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