RESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that has a poor prognosis in patients with advanced disease. Avelumab [anti-programmed death-ligand 1 (PD-L1)] became the first approved treatment for patients with metastatic MCC (mMCC), based on efficacy and safety data observed in the JAVELIN Merkel 200 trial. We report long-term overall survival (OS) data after >5 years of follow-up from the cohort of patients with mMCC whose disease had progressed after one or more prior lines of chemotherapy. PATIENTS AND METHODS: In Part A of the single-arm, open-label, phase II JAVELIN Merkel 200 trial, patients with mMCC that had progressed following one or more prior lines of chemotherapy received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term OS was analyzed. RESULTS: In total, 88 patients were treated with avelumab. At data cut-off (25 September 2020), median follow-up was 65.1 months (range 60.8-74.1 months). One patient (1.1%) remained on treatment, and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Median OS was 12.6 months [95% confidence interval (CI) 7.5-17.1 months], with a 5-year OS rate of 26% (95% CI 17% to 36%). In patients with PD-L1+ versus PD-L1- tumors, median OS was 12.9 months (95% CI 8.7-29.6 months) versus 7.3 months (95% CI 3.4-14.0 months), and the 5-year OS rate was 28% (95% CI 17% to 40%) versus 19% (95% CI 5% to 40%), respectively (HR 0.67; 95% CI 0.36-1.25). CONCLUSION: Avelumab monotherapy resulted in meaningful long-term OS in patients with mMCC whose disease had progressed following chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.
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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Células de Merkel/tratamiento farmacológico , Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/secundario , Estudios de Seguimiento , Humanos , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVE: It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end-products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study. MATERIAL AND METHODS: Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 µg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry. RESULTS: High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (≥ 500 µg/mL of LPS and ≥ 25 µg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high-glucose condition. CONCLUSIONS: A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs.
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Fibroblastos/metabolismo , Encía/metabolismo , Glucosa/farmacología , Productos Finales de Glicación Avanzada/farmacología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolisacáridos/farmacología , Porphyromonas gingivalis/metabolismo , Adulto , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/citología , Citometría de Flujo , Encía/citología , Humanos , Masculino , Adulto JovenRESUMEN
Cyclosporine-A (CsA) stimulates heme oxygenase-1 (HO-1) expression in the gingiva, but the regulation and the role of HO-1 in gingival overgrowth are not well-understood. HO-1 is regulated by several transcription factors, such as nuclear factor-κB (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf-2). The aim of this study was to examine the role of Nrf-2 in the regulation of CsA-stimulated HO-1 expression in human gingival fibroblasts. Nrf-2 siRNA (siNrf-2), NF-κB, kinase inhibitors, and sulforaphane (SFN) were used to examine the nuclear translocation of Nrf-2 and expression of HO-1 and transforming growth factor-ß1 (TGF-ß1) in cells. Treatment with siNrf-2, but not with an NF-κB inhibitor, reduced CsA-stimulated HO-1 mRNA expression. ERK inhibition significantly decreased CsA-stimulated Nrf-2 nuclear translocation and HO-1 mRNA expression. Pre-treatment with SFN showed that HO-1 plays a role in attenuating CsA-mediated TGF-ß1 expressions. These findings suggest that CsA-stimulated HO-1 expression is mediated through the activation of ERK, and that Nrf-2 plays a protective role against CsA-induced gingival fibrosis by modulating collagen turnover-related genes.
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Ciclosporina/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Sobrecrecimiento Gingival/metabolismo , Hemo-Oxigenasa 1/biosíntesis , Factor 2 Relacionado con NF-E2/fisiología , Transporte Activo de Núcleo Celular , Análisis de Varianza , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Fibroblastos/metabolismo , Técnicas de Inactivación de Genes , Encía/citología , Encía/metabolismo , Sobrecrecimiento Gingival/inducido químicamente , Hemo-Oxigenasa 1/genética , Humanos , Isotiocianatos , Sistema de Señalización de MAP Quinasas , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , FN-kappa B/metabolismo , ARN Interferente Pequeño , Estadísticas no Paramétricas , Sulfóxidos , Tiocianatos/farmacología , Factor de Crecimiento Transformador beta1/biosíntesis , Factor de Crecimiento Transformador beta1/genética , Regulación hacia ArribaRESUMEN
To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis.
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Pueblo Asiatico/genética , Obesidad/genética , Caracteres Sexuales , Adulto , Índice de Masa Corporal , Mapeo Cromosómico , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Hawaii/epidemiología , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Oportunidad Relativa , Fenotipo , San Francisco/epidemiología , Factores Sexuales , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Subjects with the metabolic syndrome are accompanied by insulin resistance (IR). However, it is not clear how well the newly defined metabolic syndrome identifies IR specifically in hypertensive subjects. AIMS: The purpose of the study was to evaluate the performance of the metabolic syndrome, defined by the American Heart Association (AHA) and the International Diabetes Federation (IDF) definitions, in identifying IR in hypertension. METHODS: The analysis is a cross-sectional study. Totally, 228 hypertensive patients and 92 non-diabetic normotensive controls who received insulin suppressive tests for direct evaluation of their insulin sensitivity were included from the Stanford Asia and Pacific Program for Hypertension and IR. McNemar's tests were used to compare sensitivity and specificity of the AHA-defined with the IDF-defined metabolic syndrome in diagnosis of IR. RESULTS: The sensitivity of the metabolic syndrome for IR in hypertension was 89.7% and the specificity 45.9% by the AHA definition. Using the IDF definition, the sensitivity was 77.6%, and the specificity increased to 63.5%. The diagnostic power of individual components of the syndrome was also modest. The predictive discrimination of wider waist circumference was similar to that of the AHA-defined metabolic syndrome. CONCLUSIONS: Use of the metabolic syndrome by the AHA definition provided good sensitivity, but low specificity to diagnose IR in hypertension. The IDF definition improved in false-positive rate, but it was still not specific enough to identify IR in hypertension.
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Hipertensión/complicaciones , Resistencia a la Insulina/fisiología , Síndrome Metabólico/diagnóstico , Adulto , Estudios de Casos y Controles , Estudios Transversales , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Sensibilidad y Especificidad , Circunferencia de la CinturaRESUMEN
The droplet impingement into a cavity at micrometer-scale is one of important fluidic issues for microfabrications, e.g. the inkjet deposition process in the PLED display manufacturing. The related micro-fluidic behaviors in the deposition process should be carefully treated to ensure the desired quality of microfabrication. The droplets generally dispensing from an inkjet head, which contains an array of nozzles, have a volume in several picoliters, while each nozzle responds very quickly and jets the droplets into cavities on substrates with micrometer size. The nature of droplet impingement depends on the fluid properties, the initial state of droplet, the impact parameters and the surface characteristics. The commonly chosen non-dimensional numbers to describe this process are the Weber number, the Reynolds number, the Ohnesorge number, and the Bond number. This paper discusses the influences of fluid properties of a Newtonian fluid, such as surface tension and fluid viscosity, on micro-fluidic characteristics for a certain jetting speed in the deposition process via a numerical approach, which indicates the impingement process consists of four different phases. In the first phase, the droplet stretching outwards rapidly, where inertia force is dominated. In the second phase, the recoiling of droplet is observed, where surface tension becomes the most important force. In the third phase, the gravitational force pulls the droplet surface towards cavity walls. The fourth phase begins when the droplet surface touches cavity walls and ends when the droplet obtains a stable shape. If the fluid viscosity is relatively small, the droplet surface touches cavity walls in the second phase. A stable fluid layer would not form if the viscosity is relatively small.
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Diseño Asistido por Computadora , Diseño de Equipo/métodos , Análisis de Falla de Equipo/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Microfluídica/instrumentación , Microfluídica/métodos , Modelos Teóricos , Simulación por Computador , Análisis de Falla de Equipo/métodos , Técnicas Analíticas Microfluídicas/métodos , Miniaturización/métodosRESUMEN
BACKGROUND: Prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation. It may reduce in diabetic patients to contribute to the platelet hyperaggregability and acceleration of atherosclerosis. While the major clinical manifestation of diabetes mellitus is increased blood levels of glucose, elevation of free fatty acids (FFA) levels in the circulation has also been reported. METHODS: Cultured rat aortic endothelial cells were treated with media containing high concentration of FFA (oleic acid 0.5 mM, palmitic acid 0.25 mM, linoleic acid 0.25 mM, stearic acid 0.06 mM, arachidonic acid 0.04 mM, total 1.1 mM, and the molar ratio of FFA/albumin < 2), glucose (22 mM) or both. Then the PGI2 release was studied by measuring 6-keto-PGF1alpha in the media. RESULTS: We found that high concentration of FFA increased the PGI2 production at basal (1.227 +/- 0.031 vs 0.762 +/- 0.028 ng/mg protein, n = 6, p = 0.002) and when stimulated by 0.5 unit/ml of thrombin (2.708 +/- 0.115 vs 1.337 +/- 0.225 ng/mg protein, n = 6, p = 0.002). Two-day treatment with high-glucose did not affect PGI2 production. However, in the presence of high-glucose, the enhancement by high FFA of thrombin stimulated PGI2 production disappeared (high-glucose 1.461 +/- 0.312 ng/mg, normal-glucose 2.708 +/- 0.115 ng/mg, n = 6, p = 0.002). CONCLUSIONS: The interaction between glucose and FFA can reduce PGI2 production in thrombin-stimulated state. Our findings further support their role in the pathogenesis of platelet hyperaggregability and acceleration of atherosclerosis in diabetes.
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Aorta/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Epoprostenol/biosíntesis , Ácidos Grasos no Esterificados/farmacología , Glucosa/farmacología , Trombina/farmacología , Animales , Aorta/metabolismo , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
A venom-specific cDNA encoding for a thrombin-like enzyme designated as mucrosobin has been cloned and sequenced from the cDNA library of the venomous gland of Trimeresurus mucrosquamatus. The full-length cDNA of mucrosobin was assembled by oligonucleotide screening and 5'-rapid amplification of cDNA ends. The amino acid sequence deduced from the cDNA consists of 257 amino acid residues with a putative signal peptide of 24 residues. It is highly homologous to the other thrombin-like enzymes (batroxobin, mucofirase, and calobin), suggesting that it is a serine proteinase with a conserved catalytic triad of His(41), Asp(84) and Ser(179) in the deduced form of mucrosobin protein. Northern blot analysis revealed that the mucrosobin gene encodes an mRNA of 1.5 kb and suggested a tissue-specific expression in the venomous gland. In an effort to study the biological property of mocrosobin, we have expressed the 28-kDa protein as inclusion bodies in Escherichia coli. For analyzing enzymatic activity, the inclusion bodies were solubilized and the recombinant protein was refolded with a two-step dialysis protocol. The refolded recombinant protein exhibited a specific beta-fibrinogenolytic activity. This study offers a possibility of using genetic engineering to acquire a functional snake venom protein with therapeutic potential.
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Venenos de Crotálidos/enzimología , Fibrinolíticos/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Escherichia coli/genética , Fibrinógeno/metabolismo , Fibrinolíticos/química , Cuerpos de Inclusión/metabolismo , Datos de Secuencia Molecular , Pliegue de Proteína , Estructura Terciaria de Proteína , Conejos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Análisis de Secuencia , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Solubilidad , Transcripción Genética , Trimeresurus/genéticaRESUMEN
An increase in circulating non-esterified fatty acids (NEFA) has been observed in patients with poorly controlled diabetes mellitus. To investigate whether fatty acids will affect the endothelin-1 (ET-1) receptor and thus contribute to the acceleration of atherosclerosis in diabetic patients, cultured rat aortic smooth muscle cells (SMC) were maintained in media containing higher (similar to those in diabetic patients) concentrations of oleic acid (OA) or linoleic acid (LA). The ET-1 binding and ET-1-stimulated thymidine uptake were then examined. We found that cells treated with OA (500 micromol/L) or LA (250 micromol/L) showed a significant increase in ET-1 receptor amount as demonstrated by Scatchard analysis (Bmax: 7.40 +/- 1.04 v 2.71 +/- 0.54 fmol/mg and 5.00 +/- 1.00 v 3.32 +/- 0.70 fmol/mg, respectively). No change in binding affinity was found. Moreover, both the basal and ET-1-stimulated thymidine uptake were enhanced by treatment with either LA (basal, 11,367 +/- 4,117 cpm/mg; LA, 13,933 +/- 4,003 cpm/mg; ET-1 (10(-8)), 16,931 +/- 4,412 cpm/mg; LA +/- ET-1 (10(-8)), 28,855 +/- 5,217 cpm/mg) or OA (basal, 4,912 +/- 1,193 cpm/mg, OA, 8,027 +/- 1,318 cpm/mg; ET-1 (10(-8)) 9,947 +/- 2,520 cpm/mg; OA + ET-1 (10(-8)), 16,761 +/- 1,740 cpm/mg). This enhancement in thymidine uptake was associated with an increase in cell number. Because ET-1 and its receptor are involved in atherogenesis, our findings suggested that increase in circulating NEFA may contribute to the acceleration of atherosclerosis in diabetic patients. Further studies to confirm its role in the vascular wall are warranted.
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Endotelina-1/metabolismo , Ácido Linoleico/farmacología , Músculo Liso Vascular/efectos de los fármacos , Ácido Oléico/farmacología , Animales , Aorta/citología , Aorta/efectos de los fármacos , Aorta/metabolismo , Células Cultivadas , Ácidos Grasos no Esterificados/sangre , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Unión Proteica , Ratas , Ratas Sprague-DawleyRESUMEN
Previously, we reported that insulin-stimulated glucose uptake (ISGU) can be inhibited by endothelin (ET-1). However, the mechanism by which ET-1 impairs ISGU in adipocytes remains unclear. This study investigated the effects of ET-1 on insulin action in rat adipocytes in order to elucidate the molecular mechanism of action of ET-1 on ISGU. The results show that ISGU was increased fivefold after 3-h treatment with 1 nM insulin. Treatment with 100 nM ET-1 had no effect on basal glucose uptake. However, ET-1 inhibited approximately 25% of ISGU and 20% of insulin binding after 3-h treatment in the presence of 1 nM insulin. Expression of the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS-1) in adipocytes was not significantly affected by 1 nM insulin or by 100 nM ET-1, even after 3-h treatment. However, expressions of IRbeta and IRS-1 were dramatically decreased in a dose- and time-dependent manner when adipocytes were treated with both insulin and ET-1. Approximately 50% of IRbeta and 65% of IRS-1 expression levels were suppressed when adipocytes were simultaneously treated with both 1 nM insulin and 100 nM ET-1 for 3 h. These results suggest that the inhibitory effect of ET-1 on ISGU may be mediated via the insulin receptor and suppression of IRbeta/IRS-1 expression.
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Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Endotelina-1/administración & dosificación , Glucosa/metabolismo , Insulina/administración & dosificación , Fosfoproteínas/metabolismo , Receptor de Insulina/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Interacciones Farmacológicas , Técnicas In Vitro , Proteínas Sustrato del Receptor de Insulina , Cinética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: To investigate the insulin sensitivity in normotensive offspring of hypertensive parents. SUBJECTS: Fifteen young normotensive offspring of hypertensive parents were paired with 15 controls matched for age, sex and body mass index. METHODS: The insulin sensitivity was investigated by 75 g oral glucose tolerance test (OGTT) and modified insulin suppression test. A high-fat mixed meal was administered to observe the changes of TG levels. RESULTS: The plasma glucose and serum insulin responses to oral glucose challenge were comparable between both groups. High-fat mixed meal made no difference in the plasma glucose, serum triglyceride or insulin between the 2 groups. With the modified insulin suppression test, the steady-state plasma glucose levels (SSPG) were higher in the offspring of parents with essential hypertension (138+/-43 mg/dl) than in the control group (95+/-26 mg/dl). The diastolic blood pressure and heart rate of the offspring of hypertensive parents are also higher than the control group. CONCLUSIONS: Insulin resistance exists in young normotensive offspring of hypertensive parents, and the impairment of insulin-mediated glucose uptake in these subjects develop before any alteration of fasting and postprandial triglyceride.
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Presión Sanguínea , Hipertensión/genética , Insulina/sangre , Adulto , Glucemia/metabolismo , Composición Corporal , Constitución Corporal , Diástole , Grasas de la Dieta , Femenino , Prueba de Tolerancia a la Glucosa , Frecuencia Cardíaca , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Núcleo Familiar , Valores de Referencia , Triglicéridos/sangreRESUMEN
AIMS: To evaluate the effects of simvastatin on serum lipids and insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia. METHODS: A double-blind, randomized, placebo-controlled and two-period crossover study. After a 2-month run-in, 19 eligible Type 2 diabetic patients with hypercholesterolaemia were randomized to receive either simvastatin or placebo for 3 months, exchanging their treatment thereafter for another 3 months. Blood samples were taken in month 0 and at monthly intervals to measure serum lipids and indices of glycaemic control. An euglycaemic insulin clamp was performed in months 0, 3 and 6 to assess change of insulin sensitivity. The amount of glucose infused during 90-120 min of the clamp (M), and the mean values of serum insulin during 90-120 min (I) were measured. The M and M/I ratio were used to represent the in vivo insulin sensitivity of the subject. RESULTS: Simvastatin significantly reduced serum total cholesterol (TC) by 23+/-18% and low density lipoprotein-cholesterol (LDL-C) by 30+/-26%. It did not alter glycaemic control. The M-values and M/I ratios were similar in both groups in each period and no drug effect on insulin sensitivity could be identified. CONCLUSIONS: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.
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Anticolesterolemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Hipercolesterolemia/tratamiento farmacológico , Insulina/farmacología , Simvastatina/uso terapéutico , Adulto , Anciano , Anticolesterolemiantes/efectos adversos , Glucemia/metabolismo , Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipercolesterolemia/etiología , Masculino , Persona de Mediana Edad , Placebos , Simvastatina/efectos adversosRESUMEN
We report the case of a 17-year-old adolescent boy with polyostotic fibrous dysplasia and hypersecretion of growth hormone (GH). The fasting serum GH, insulin-like growth factor-I (IGF-I), alkaline phosphatase activity and osteocalcin levels were all elevated. The GH secretion was stimulated by thyrotropin-releasing hormone and was not suppressed by an oral glucose test. Magnetic resonance imaging of the sella turcica showed no abnormal findings. The patient was treated with octreotide, 100 micrograms subcutaneous injection three times a day for two weeks to observe the effects of octreotide on growth hormone secretion. GH and IGF-I secretions were suppressed by octreotide therapy, while alkaline phosphatase activity and osteocalcin secretion were partially suppressed. We suggest that the high bone turnover states in this patient may be attributed to both hypersecretion of growth hormone and the polyostotic fibrous dysplasia itself.
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Displasia Fibrosa Poliostótica/tratamiento farmacológico , Hormona de Crecimiento Humana/metabolismo , Octreótido/uso terapéutico , Adolescente , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Osteocalcina/sangreRESUMEN
BACKGROUND: The aim of this study was to evaluate the clinical response and patient acceptance of a prefilled, disposable insulin pen injector (Novolet, Novo-Nordisk, Bagsvaerd, Denmark) for treating insulin-dependent diabetic patients. METHODS: After a run-in period of six weeks, 19 patients participated in an open, randomized, controlled, crossover study with two 12-week periods using insulin pens or conventional syringes. Clinical responses were assessed every 12 weeks, including glycosylated hemoglobin (HbA1c), seven-point blood glucose profiles and hypoglycemic reactions. At the end of the trial, patients completed questionnaires about their acceptance of the insulin delivery device. RESULTS: Neither of the regimens rendered significant changes in HbA1c, blood glucose profiles or hypoglycemic episodes. Most of the study subjects reported that the prefilled, disposable devices were convenient and easy to use, and many of them wished to continue using the device for insulin delivery. CONCLUSIONS: The clinical response was the same for both treatment regimens, but most subjects preferred the prefilled disposable pen injector for insulin delivery because it was more convenient for daily use.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inyecciones/instrumentación , Insulina/administración & dosificación , Aceptación de la Atención de Salud , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The Sensorex (Metertech, Taipei, Taiwan), an electrochemical blood glucose meter, is designed for self-monitoring of blood glucose (BG) concentrations in capillary blood through the use of an electrochemical test strip. The intra-assay coefficients of variation of Sensorex were 5.2, 5.4, and 4.7% at BG levels of 46, 154 and 302 mg/dl respectively. The BG concentrations tested by Sensorex were correlated well with those by YSI method (r approximately/= 0.85, P < 0.0001). The intraclass correlation coefficients (rI) between the results obtained by Sensorex and YSI were 0.84 in capillary blood and 0.69 in venous whole blood, which indicated good agreement between both methods. The Sensorex was evaluated by error grid analysis and revealed 'acceptance' results. In field test, the Sensorex results obtained by lay users were in concordance with those by trained technicians (rI = 0.87). Our data show that the Sensorex glucometer is reliable and easy to use. We also demonstrate a practical clinical approach for the evaluation of a novel SMBG system.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Diabetes Mellitus/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Automonitorización de la Glucosa Sanguínea/métodos , Capilares , Electroquímica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiras Reactivas , Análisis de Regresión , Reproducibilidad de los Resultados , VenasRESUMEN
The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults. The patients were randomized into a double-blind, placebo-controlled study of human recombinant GH replacement therapy for 6 months (period 1), followed by an open phase of GH for another 6 months (period 2). Anthropometric variables, body fat composition (fat %), and biochemical parameters were measured during the trial. Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test. The modified insulin suppression test was performed both in the morning (AM) and in the afternoon (PM) to further evaluate the PM-AM steady-state plasma glucose (SSPG) pattern. We found that the GH-deficient adults had more body fat and were insulin resistant. Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight. Besides, we demonstrated, for the first time, the GH replacement for 6 months did not alter the insulin sensitivity, but replacement for a longer period (12 months) normalized not only the AM SSPG level but also the PM-AM SSPG pattern. We also found a positive correlation between SSPG (regardless of AM vs. PM) and fat % and total body fat mass. In conclusion, normalization of insulin sensitivity in GH-deficient adults after replacement of GH may be related to the reduction of total body fat.
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Tejido Adiposo/patología , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Resistencia a la Insulina , Adulto , Glucemia/análisis , Composición Corporal/efectos de los fármacos , Ritmo Circadiano , Método Doble Ciego , Femenino , Homeostasis , Humanos , Masculino , Valores de ReferenciaRESUMEN
Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Hiperlipidemias/complicaciones , Hipertrigliceridemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Pirazinas/uso terapéutico , Adulto , Anciano , Apolipoproteína A-I/análisis , Apolipoproteína A-I/efectos de los fármacos , Apolipoproteínas B/análisis , Apolipoproteínas B/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hiperlipidemias/sangre , Hipertrigliceridemia/sangre , Insulina/fisiología , Lipoproteínas HDL/análisis , Lipoproteínas HDL/efectos de los fármacos , Lipoproteínas LDL/análisis , Lipoproteínas LDL/efectos de los fármacos , Masculino , Persona de Mediana Edad , Triglicéridos/análisis , Triglicéridos/sangreRESUMEN
BACKGROUND: Lovastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in the treatment of hypercholesterolemia. It is also applied to dyslipidemia in patients with diabetes mellitus. The influence of lovastatin on insulin sensitivity was evaluated in twelve Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolemia. METHODS: This double-blind, randomized, placebo-controlled, and two-period cross-over experiment enrolled 12 patients. After a run-in period of two months, the patients were randomized into 2 groups to receive either lovastatin (20 mg once daily) or placebo treatment. Eight weeks later, two groups of patients exchanged their treatment for another 8 weeks. Blood samples were collected at the end of the run-in period and at 4-week intervals during the study to observe serum lipid profiles. A modified insulin suppression test was made to assess insulin sensitivity three times: at the end of run-in period, in week 8 and week 16, respectively. Wilcoxon signed rank test was used for analysis of statistical significance of the difference between lovastatin and placebo treatments. RESULTS: As compared with the placebo, lovastatin reduced serum total cholesterol (TC) levels significantly. Serum total triglyceride (TG) concentrations decreased slightly by lovastatin. The ratio of TC to high density lipoprotein-cholesterol (HDL-C) also decreased significantly in lovastatin period. No difference was found in serum apolipoprotein A1 levels. A significant reduction of serum apolipoprotein B concentrations was also noted in lovastatin period. No difference in glycemic indices and insulin sensitivity was observed in the base-line, placebo or lovastatin periods. CONCLUSIONS: The results demonstrated that lovastatin significantly lowered the serum TC levels without perturbation of insulin sensitivity in hypercholesterolemic NIDDM patients.