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1.
Contemp Clin Trials ; 36(2): 515-26, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24080100

RESUMEN

BACKGROUND: Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. PURPOSE: The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. METHODS: DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. CONCLUSION: Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada/análisis , Periodontitis/terapia , Glucemia/análisis , Protocolos Clínicos , Diabetes Mellitus Tipo 2/sangre , Humanos , Antisépticos Bucales/uso terapéutico , Periodontitis/sangre , Periodontitis/etiología , Índice de Severidad de la Enfermedad , Método Simple Ciego
2.
Eur J Gynaecol Oncol ; 33(4): 363-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23091891

RESUMEN

Obesity results in increased mortality from many forms of cancer. We looked at the levels of gene expression for TNFalpha, IL-6, IkappaB kinase (inhibitor of NF-kappaB), CD 68 (glycoprotein expressed on macrophages) and leptin in samples of adipose tissue from individuals with endometrial cancer versus patients with benign conditions. This is a prospective study which included patients of a gynecologic oncology group. A piece of omental tissue was harvested from them during surgery. RNA was purified from all samples. Relative amounts of RNA for IkappaB, TNFalpha, IL-6, CD68 and leptin were calculated. Pearson's correlation method was used to correlate RNA levels with BMI. Logistic regression method was used to compare gene expression for cancer and control groups. The total sample size was 56 (24 endometrial cancer and 32 controls). IkappaB, TNFalpha and IL-6 levels increased linearly with increasing BMI in the control group. There was no correlation of IkappaB, TNFalpha, IL-6 or CD-68 levels with cancer status of the patients. Leptin had a weak protective effect against endometrial cancer (odds ratio = 0.92). Obesity is associated with increased expression of certain inflammatory cytokines in the adipose tissue. However, increased levels of these inflammatory markers in the adipose tissue of the omentum are not associated with presence of endometrial cancer.


Asunto(s)
Tejido Adiposo/metabolismo , Citocinas/genética , Neoplasias Endometriales/etiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Citocinas/fisiología , Neoplasias Endometriales/inmunología , Femenino , Humanos , Leptina/sangre , Modelos Logísticos , Persona de Mediana Edad , FN-kappa B/fisiología , Obesidad/complicaciones , Estudios Prospectivos
3.
Diabetes Obes Metab ; 10(2): 151-8, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18190429

RESUMEN

AIM: Multidrug regimens in HIV disease are associated with an increased incidence of insulin resistance, by as much as 50%. Not only does insulin resistance predisposes subjects to diabetes but also it is associated with the metabolic syndrome and increased risk of cardiovascular disease. Previous studies suggest that chromium picolinate can improve insulin resistance in patients with type 2 diabetes. The objective was to study the efficacy and safety of chromium picolinate as a treatment of insulin resistance in subjects infected with HIV. METHODS: The ability of chromium picolinate (1000 mug/day) to improve insulin sensitivity, determined with a hyperinsulinaemic-euglycaemic insulin clamp, was determined in eight HIV-positive subjects on highly active antiretroviral therapy. RESULTS: The mean rate of glucose disposal during the clamp was 4.41 mg glucose/kg lean body mass (LBM)/min (range 2.67-5.50), which increased to 6.51 mg/kg LBM/min (range 3.19-12.78, p = .03), an increase of 25% after 8 weeks of treatment with chromium picolinate. There were no significant changes in blood parameters, HIV viral burden or CD4+ lymphocytes with chromium picolinate treatment. Two subjects experienced abnormalities of liver function during the study. Another subject experienced an elevation in blood urea nitrogen. CONCLUSIONS: The study shows that chromium picolinate therapy improves insulin resistance in some HIV-positive subjects, but with some concerns about safety in this population.


Asunto(s)
Resistencia a la Insulina/fisiología , Quelantes del Hierro/uso terapéutico , Ácidos Picolínicos/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Femenino , Técnica de Clampeo de la Glucosa/instrumentación , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Ácidos Picolínicos/administración & dosificación , Ácidos Picolínicos/efectos adversos , Proyectos Piloto , Resultado del Tratamiento
4.
Clin Sci (Lond) ; 101(6): 583-9, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11724643

RESUMEN

HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease.


Asunto(s)
Proteínas Sanguíneas/biosíntesis , Infecciones por VIH/sangre , Linfocitos/metabolismo , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Antropometría , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismo , Carga Viral
6.
J Acquir Immune Defic Syndr ; 25(4): 312-21, 2000 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11114831

RESUMEN

HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor-alpha (TNF-alpha) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p <.05) closely correlated with the reduced peripheral insulin sensitivity (p =. 0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p =.0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy.


Asunto(s)
Infecciones por VIH/complicaciones , Resistencia a la Insulina/fisiología , Lipodistrofia/complicaciones , Receptores del Factor de Necrosis Tumoral/sangre , Absorciometría de Fotón , Tejido Adiposo , Adulto , Composición Corporal , Ensayo de Inmunoadsorción Enzimática , Ácidos Grasos/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/análisis , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Masculino , ARN Viral/sangre , Radioinmunoensayo , Estadísticas no Paramétricas
7.
J Pediatr Endocrinol Metab ; 13 Suppl 2: 1023-9, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11086657

RESUMEN

Over the past several years, we have studied a variety of clinical conditions that are characterized by significant alterations in the GH/IGF system that might contribute to catabolism. Our studies have focused in detail on IGF-I and -II and the major IGFBPs in the circulation, IGFBP-3, -1, and -2; GH was also measured in some of these studies. In light of a recent study that has raised concerns about the use of GH in critically ill patients, we now review the changes in the GH/IGF axis during critical illness, the interaction between cytokines and the GH/IGF axis, and the safety and efficacy of GH therapy in critical illness. We conclude that it is premature to recommend interruption of GH therapy in patients with documented GH deficiency during periods of acute illness.


Asunto(s)
Enfermedad Crítica , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Animales , Humanos
8.
J Acquir Immune Defic Syndr ; 22(1): 49-55, 1999 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-10534146

RESUMEN

The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups. The serum concentrations of IGFBP-1 and IGFBP-2 were significantly higher in AIDS patients with wasting than in the other three groups (p < .05). In addition, there was a statistically significant positive correlation between the levels of IGFBP- 1 (p = .004) and IGFBP-2 (p = .03) and the stage of disease. Following GH administration, the serum concentrations of insulin and IGF-I were increased in all groups (p < .05). In addition, the increases in insulin levels correlated with stage of disease (p = .004). The responses of the IGFBPs were more variable. GH administration significantly increased the levels of IGFBP-3 in all groups except the patients with AIDS wasting, whereas the levels of IGFBP-1 were significantly decreased in controls and AIDS patients. These results demonstrate that there is a continuum of both elevations in the IGFBPs and altered metabolic responsiveness in patients infected with HIV that increases with the severity of the disease. These data also demonstrate that AIDS patients, who are free from secondary infection, respond to administration of GH by significantly increasing hepatic IGF-I production.


Asunto(s)
Hormona del Crecimiento/farmacología , Infecciones por VIH/fisiopatología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Hormona del Crecimiento/administración & dosificación , Síndrome de Emaciación por VIH/fisiopatología , Hormona de Crecimiento Humana , Humanos , Inyecciones , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Autoadministración , Pérdida de Peso
9.
J Clin Endocrinol Metab ; 83(9): 3050-5, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9745402

RESUMEN

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P < 0.001), and patients with AIDS and > 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , Huesos/metabolismo , Colágeno/biosíntesis , Seropositividad para VIH/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Albúmina Sérica/biosíntesis , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Femenino , Síndrome de Emaciación por VIH/tratamiento farmacológico , Humanos , Masculino , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Pérdida de Peso
10.
J Nutr ; 128(2 Suppl): 356S-359S, 1998 02.
Artículo en Inglés | MEDLINE | ID: mdl-9478024

RESUMEN

This paper examines the role of hormones in the normal responses of muscle protein synthesis to nutrient intake and the use of hormones to improve the effects of nutritional therapies in patients with protein-wasting conditions. In growing rats, the increase in muscle protein synthesis after feeding seems to be mediated by the rise in plasma insulin and also by an enhanced sensitivity of the muscle to insulin brought about by the amino acid leucine. In adult rats, however, the responsiveness of muscle to both feeding and insulin is much reduced, suggesting that changes in protein degradation play an important role in the response to feeding. Similarly, in adult humans, muscle protein synthesis is not affected by insulin, but is stimulated by insulin-like growth factor (IGF)-I and growth hormone (GH). The effect of GH treatment has been studied in a number of different groups of patients suffering from protein wasting, and improvements in nitrogen balance and lean body mass have been reported. In a study of patients with acquired immunodeficiency syndrome (AIDS), however, GH treatment for 2 wk caused a fall in muscle protein synthesis in the patients with wasting, despite an increase in healthy controls, suggesting that the responsiveness of muscle to the hormone may be altered by the stage of the disease.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Infecciones por VIH/metabolismo , Hormonas/fisiología , Proteínas Musculares/metabolismo , Fenómenos Fisiológicos de la Nutrición/fisiología , Animales , Infecciones por VIH/clasificación , Infecciones por VIH/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Insulina/fisiología , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/farmacología , Metilhistidinas/orina , Ratones , Proteínas Musculares/efectos de los fármacos
11.
Endocrinology ; 138(10): 4153-9, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9322924

RESUMEN

Tumor necrosis factor-alpha (TNF-alpha) induces cachexia and is postulated to be responsible for muscle wasting in several pathophysiological conditions. The purpose of the present study was to investigate whether exposure of human myoblasts to TNF-alpha could directly inhibit the ability of serum or insulin-like growth factor I (IGF-I) to stimulate protein synthesis as assessed by the incorporation of [3H]phenylalanine into protein. Serum and IGF-I stimulated protein synthesis dose dependently. Half-maximal stimulation of protein synthesis occurred at 05% serum and 8 ng/ml of IGF-I, respectively. TNF-alpha inhibited IGF-I-stimulated protein synthesis in a dose-dependent manner. Additionally, as little as 2 ng/ml of TNF-alpha impaired the ability of IGF-I to stimulate protein synthesis by 33% and, at a dose of 100 ng/ml, TNF-alpha completely prevented the increase in protein synthesis induced by either serum or a maximally stimulating dose of IGF-I. Inhibition of protein synthesis was independent of whether TNF-alpha and growth factors were added to cells simultaneously or if the cells were pretreated with growth factors. Exposure ofmyoblasts to TNF-alpha for 10 min completely inhibited serum-induced stimulation of protein synthesis. TNF-alpha inhibited protein synthesis up to 48 h after addition of the cytokine. TNF-alpha also inhibited serum-stimulated protein synthesis in human myoblasts that were differentiated into myotubes. In contrast, exposure of myoblasts to TNF-alpha had no effect on IGF-I binding and failed to alter the ability of either IGF-I or serum to stimulate [3H]thymidine uptake. These data indicate that transient exposure of myoblasts or myotubes to TNF-alpha inhibits protein synthesis. Thus, the anabolic actions of IGF-I on muscle protein synthesis may be impaired during catabolic conditions in which TNF-alpha is over expressed.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina/farmacología , Proteínas Musculares/biosíntesis , Músculo Esquelético/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Células Cultivadas , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Fenilalanina/metabolismo , Timidina/metabolismo , Tritio
12.
J Clin Invest ; 100(8): 2125-32, 1997 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-9329979

RESUMEN

This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.


Asunto(s)
Síndrome de Emaciación por VIH/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Proteínas Musculares/biosíntesis , Músculo Esquelético/metabolismo , Adulto , Metabolismo Basal , Progresión de la Enfermedad , Resistencia a Medicamentos , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Metilhistidinas/orina , Contracción Muscular/fisiología , Músculo Esquelético/efectos de los fármacos , Miofibrillas/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Carga Viral , Aumento de Peso/efectos de los fármacos
13.
Endocrine ; 7(1): 81-5, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9449038

RESUMEN

Over the last several years, the authors have studied the relationship of insulin-like growth factors (IGFs) and the insulin-like growth factor binding proteins (IGFBPs) in the circulation in a number of clinical settings. Patterns have emerged that seem to be characteristic of various conditions. In aging, there are marked decreases in IGF-I and -II, normal levels of IGFBP-3, and marked increases in IGFBP-1 in serum. Using ligand blotting and an IGFBP-3 proteolysis assay, BP-3 is intact. Based on native gel electrophoresis, IGFBP-1 is in its most highly phosphorylated state in those elders who have high IGFBP-1 levels. This pattern is slightly different in catabolic conditions such as AIDS (wasting in adults; failure to thrive in children), uncontrolled diabetes mellitus, trauma, and severe burns. In these conditions, serum levels of IGF-I and -II are markedly diminished, IGFBP-3 levels are also decreased, and IGFBP-1 levels are markedly increased. In addition, there is increased proteolysis of IGFBP-3 (AIDS failure to thrive, uncontrolled diabetes mellitus) and disruption of the ternary complex with decreased levels of ALS (AIDS wasting and burns). IGFBP-1 is in its most highly phosphorylated state in all catabolic conditions studied. Thus, the alterations in the circulating levels of IGFs and the changes in the physical state of the IGFBPs may lead to decreased anabolic activity and be a part of the mechanism of increased catabolism and wasting.


Asunto(s)
Anciano Frágil , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Debilitante/sangre
14.
Am J Physiol ; 273(1 Pt 2): R371-8, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9249574

RESUMEN

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.


Asunto(s)
Hormona de Crecimiento Humana/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lipopolisacáridos/farmacología , Adolescente , Adulto , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Endotoxinas/administración & dosificación , Endotoxinas/farmacología , Escherichia coli , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Insulina/sangre , Recuento de Leucocitos/efectos de los fármacos , Lipopolisacáridos/administración & dosificación , Masculino , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Factores de Tiempo , Resistencia Vascular/efectos de los fármacos
15.
J Clin Endocrinol Metab ; 81(12): 4379-84, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8954045

RESUMEN

A small portion of circulating insulin-like growth factor I (IGF-I) is detected in the free or readily dissociable state, which is thought to be the metabolically active form. The amount of free/dissociable IGF-I in serum is dependent on a complex interplay between the production rate and the concentrations of IGF-I and IGF-binding proteins (IGFBPs). IGF availability is also influenced by posttranslational changes in IGFBPs that affect the affinity of IGFBPs for IGF-I. In the present study, we examined whether a short term fast (approximately 12 h) alters the serum concentration of free/dissociable IGF-I, and whether these changes are associated with alterations in IGFBP-1 and the proteolysis status of IGFBP-3. Circulating free/dissociable IGF-I concentrations, as assessed by a two-site immunoradiometric assay, did not differ between fasting and 4 h after a morning meal (1.48 +/- 0.07 vs. 1.50 +/- 0.07 microgram/L, respectively). Likewise, free/dissociable IGF-I levels measured by RIA after separation by centrifugal ultrafiltration were not different between the two groups (1.43 +/- 0.14 vs. 1.38 +/- 0.18 microgram/L, respectively). IGF-I bioactivity, as measured by thymidine incorporation by fibroblasts, did not differ in fasting and 4-h postprandial sera. There was no difference in IGFBP-3 and total acid-ethanol-extractable IGF-I concentrations in serum from fasted and fed subjects. In contrast, the concentration of IGFBP-1 in the serum was increased approximately 5-fold in the fasted state compared to fed values. IGFBP-1 existed in a highly phosphorylated form under fasting conditions. There was no change in IGFBP-3 proteolysis assessed either in vivo or in vitro between the fasting and fed states. The results indicate that a physiologically relevant short term overnight fast does not alter the circulating levels of free/dissociable IGF-I despite a marked elevation in IGFBP-1.


Asunto(s)
Ayuno , Factor I del Crecimiento Similar a la Insulina/análisis , Adulto , Glucemia/análisis , Femenino , Humanos , Hidrocortisona/sangre , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Masculino , Fosforilación
16.
J Intellect Disabil Res ; 40 ( Pt 6): 509-17, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9004111

RESUMEN

We have found that some children with Down's syndrome (DS) have growth retardation secondary to growth hormone (GH) deficiency. To test the hypothesis that hypothalamic dysfunction is the primary cause for GH deficiency and growth retardation, hypothalamic-pituitary responses of serum GH concentrations to levodopa and clonidine as well as pituitary responses in serum GH concentrations to growth-hormone-releasing hormone (GHRH) were analysed in 14 prepubertal children with DS. Levodopa and clonidine were given, and blood was drawn for determining serum GH levels. Seven prepubertal control children had both levodopa and clonidine tests done. The delta serum GH during levodopa was 5.7 +/- 6.3 ng ml-1 in DS and 13.1 +/- 9.8 ng ml-1 in controls. The delta serum GH during clonidine administration was 3.0 +/- 3.2 ng ml-1 in DS and 17.3 +/- 5.6 ng ml-1 in controls. Children with DS had a significantly lower response to levodopa and clonidine, compared with controls by the Mann-Whitney U-test (P < 0.03 and P < 0.009, respectively). Growth-hormone-releasing hormone was given at 1 microgram kg-1 i.v. bolus and bloods for GH were drawn at-15, 0, 15, 30, 60, 90 and 120 min in 14 subjects with DS and 24 normal controls, both groups prepubertal. The mean delta serum GH concentration in DS was 53.6 +/- 38.3 ng ml-1, and it was 35.6 +/- 25.1 ng ml-1 in controls with P < 0.23 non-significant by the Mann-Whitney U-test. These results indicate that levodopa and clonidine (drugs stimulating hypothalamic GHRH release and secondary pituitary GH release in normal individuals) do not stimulate GH release in DS. Furthermore, normal GH response to GHRH in DS indicates normal pituitary function (normal somatotroph response to GHRH) and supports hypothalamic dysfunction in DS.


Asunto(s)
Síndrome de Down/fisiopatología , Enanismo Hipofisario/fisiopatología , Hormona de Crecimiento Humana/deficiencia , Enfermedades Hipotalámicas/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Antropometría , Preescolar , Clonidina , Síndrome de Down/diagnóstico , Enanismo Hipofisario/diagnóstico , Femenino , Hormona Liberadora de Hormona del Crecimiento , Hormona de Crecimiento Humana/sangre , Humanos , Enfermedades Hipotalámicas/diagnóstico , Lactante , Levodopa , Masculino , Valores de Referencia
17.
Biochem Biophys Res Commun ; 228(2): 611-5, 1996 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-8920958

RESUMEN

TNF alpha and IL-1 beta have previously been shown to increase the IGFBP-1 concentration in plasma and liver under in vivo conditions. The present study demonstrates that another inflammatory cytokine, IL-6, also elevates a 30- to 32-kDa IGF binding protein in the plasma of mice. Moreover, IL-6 produced dose- and time-dependent increases in IGFBP-1 production by HepG2 cells. The maximal IL-6-induced increase in IGFBP-1 was comparable to that observed with dexamethasone, and this increase was attenuated by diltiazem or dantrolene, both of which are known to reduce the cytosolic Ca2+ concentration. Finally, incubation of HepG2 cells with TNF alpha or IL-1 beta also increased IGFBP-1 in a dose-dependent manner. These results demonstrate that IGFBP-1 production is mediated directly by proinflammatory cytokines and suggest that this mechanism may be important for the upregulation of IGFBP-1 seen in catabolic conditions associated with overexpression of these cytokines.


Asunto(s)
Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/biosíntesis , Interleucina-6/farmacología , Animales , Línea Celular , Dantroleno/farmacología , Diltiazem/farmacología , Relación Dosis-Respuesta a Droga , Endotoxinas/farmacología , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Cinética , Masculino , Ratones , Proteínas Recombinantes/farmacología , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/farmacología
18.
J Clin Endocrinol Metab ; 81(8): 2957-62, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8768858

RESUMEN

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.


Asunto(s)
Insuficiencia de Crecimiento/etiología , Seropositividad para VIH/complicaciones , Seropositividad para VIH/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Péptido Hidrolasas/metabolismo , Western Blotting , Niño , Preescolar , Electroforesis en Gel de Poliacrilamida , Humanos , Lactante , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/química , Factor I del Crecimiento Similar a la Insulina/metabolismo
19.
J Clin Endocrinol Metab ; 81(7): 2474-80, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8675563

RESUMEN

The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake of IGF-I by the leg in burn patients that may serve to counteract the catabolic state.


Asunto(s)
Quemaduras/sangre , Homeostasis , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adolescente , Adulto , Arterias , Niño , Carbohidratos de la Dieta/administración & dosificación , Nutrición Enteral , Femenino , Humanos , Ensayo Inmunorradiométrico , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Pierna/irrigación sanguínea , Masculino , Venas
20.
Clin Endocrinol (Oxf) ; 44(5): 501-14, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8762726

RESUMEN

OBJECTIVE: The aim of this investigation was to characterize the GH-IGF axis of patients with AIDS associated wasting. A special emphasis was placed on determining whether IGF binding proteins (IGFBPs) of patients who have lost more than 10% of their ideal body mass are structurally different from the IGFBPs of patients with no weight loss. DESIGN AND PATIENTS: A cross-sectional study of 11 AIDS patients was performed to determine whether the IGF system is abnormal in AIDS patients with wasting. Seven additional AIDS patients were followed longitudinally to determine whether AIDS patients experience long-term changes to their IGF system. MEASUREMENTS: Serum levels of GH and IGF-I were measured by radioimmunoassay, IGF-II was measured by radioreceptor assay, and IGFBP-1 was measured by an enzyme linked immunoassay. IGFBP-3 and IGFBP-3 protease activity were measured by ligand blotting and a BP-3 protease assay, respectively. IGFBP-3 ternary complex formation and IGFBP-1 phosphovariants were analysed by non-denaturing PAGE. RESULTS: AIDS patients who had lost more than 10% of their ideal body mass demonstrated a 55% reduction in serum IGF-I (81 vs 179 micrograms/l) and a 70% reduction in IGF-II (226 vs 776 micrograms/l), compared to healthy HIV negative subjects. IGF-I levels were depressed, in some patients, despite high serum levels of GH. AIDS patients who had lost more than 10% of their ideal body mass had low levels of IGFBP-3 and a reduced ability to form the IGFBP-3 ternary complex. The IGFBP-3 ternary complex could be restored only upon addition of pure IGFBP-3 and acid labile subunit to serum. Serum IGFBP-1 was increased more than threefold compared to control subjects (90 vs 24 micrograms/l). IGFBP-1 was present as a free phosphoprotein in AIDS patients with low levels of IGF-I and in a bound form when serum IGF-I levels were normal. Changes in the GH-IGF axis were sustained for up to 25 months in AIDS patients with wasting. CONCLUSIONS: AIDS wasting is associated with a GH resistant state that results in low levels of serum IGF-I, IGF-II and IGFBP-3, elevated levels of phosphorylated IGFBP-1, and a reduced ability to form the IGFBP-3 ternary complex.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/sangre , Emaciación/sangre , Hormona del Crecimiento/sangre , Somatomedinas/metabolismo , Estudios Transversales , Electroforesis en Gel de Poliacrilamida , Emaciación/virología , Endopeptidasas/sangre , Femenino , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Estudios Longitudinales , Masculino , Fosforilación , Unión Proteica , Ensayo de Unión Radioligante
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