M. Foss - Academia.edu (original) (raw)
Papers by M. Foss
Journal of Biomedical Materials Research Part A, 2011
We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalize... more We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalized with osteopontin (OPN) in a matrix of poly‐D,L‐lactic‐acid (PDLLA). In a canine endosseus 0.75‐mm gap implant model, we tested the osteointegrative impact of the OPN functionalized composite as an implant coating, and a non‐functionalized composite was used as reference control. During the four weeks of observation, the OPN functionalized composite coating significantly increased the formation of new bone in the porosities of the implant, but no differences were observed in the gap. The study provides evidence of its potential use either alone or in combination with other osteoconductive compounds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 94–101, 2011.
Medicine & Science in Sports & Exercise, 1981
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
ABSTRACT Background: Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destr... more ABSTRACT Background: Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic beta cells, which are responsible for insulin-producing. Type 2 diabetes (T2D) is a phenotypic and genetically heterogeneous chronic disease characterized by insulin resistance and deficient beta-cell function, being the most prevalent type of diabetes, accounts for 90% of all cases of diabetes. The standard definition of gestational diabetes mellitus (GDM) is the abnormal glucose metabolism diagnosed during pregnancy. Although these three types of diabetes are clinically well defined and T1D is the type more associated to the genetic background, little is known on the genetic contribution to T2D or GDM. Objectives: To compare/contrast the transcriptome profiling of peripheral blood mononuclear cells (PBMC) from patients presenting T1D, T2D or GDM by using the microarray technology allowing identifying the common or the exclusive differentially expressed genes, which characterize the three types of DM. Methods: One-color Agilent 4x44K whole functional genome microarray hybridizations of samples from T1D (n=19), T2D (n=20) or GDM (n=17) patients were quantified and data analyzed using bioinformatics pipeline included in the GeneSpring GX11 pack (Agilent). Cluster-TreeView algorithm was used to average hierarchical clustering of genes using Pearson uncentered metrics. Finally, DAVID functional analysis tool was used to analyze the functional clusters of interest. Results: Differentially expressed genes between patients of three types of diabetes were identified and classified according to: (i) association with biological regulation, immune response and insulin gene cluster (Venn diagram); (ii) DAVID functional clusters categories: T1D (INS, IGF2, HLA-G, HLA-E and GAD1), T2D (SOCS1, SOCS2, SOCS3, SOCS4, IGF2 and INS) and a third cluster identified by GOTERM_BP_FATIGO: response to corticosteroid stimulus and GO:0051384~response to glucocorticoid stimulus (GHR, TRH, FOS, CCND1 and HSD11B2). Conclusion: i) PBMC were adequate for the use as reporter cells to analyze the transcriptome profiling in DM, ii) although the three types of DM may present distinct etiopathogenic mechanisms, they exhibit shared modulated immune response and metabolism response genes, suggesting common pathways in the pathophysiology. Support: FAPESP, CNPq and CAPES (Brazil).
Human Immunology, 2014
Gestational diabetes mellitus (GDM) is the most common metabolic disorder observed during pregnan... more Gestational diabetes mellitus (GDM) is the most common metabolic disorder observed during pregnancy, and has been defined as an abnormal glucose metabolism first diagnosed during gestation. GDM women usually present postpartum diabetes, insulin resistance, metabolic syndrome, hypertension and dyslipidemia. Although few genetic markers have been described for GDM, approximately 10% of GDM patients present high probability of progression to type 1 diabetes (T1D). In a previous meta-analysis study, evaluating the transcript profiles of patients with the major types of diabetes, we reported that transcription profile of T1D patients was closer to GDM than to type 2 diabetes. Additionally, it has already been reported association of some HLA alleles with GDM, suggesting a possible immunological feature for GDM. In this study, we compared the transcription profiling of PBMCs of 18 GDM patients and 10 healthy pregnant women. Total RNA samples were hybridized to Agilent® 4 × 44 K oligo microarrays encompassing the whole human functional genome. Differentially expressed mRNAs were obtained by Rank Products analysis, which classifies transcripts according to their fold change values. The hierarchical clustering of mRNAs and samples were performed using the Cluster program, dendrograms and spatial representations of mRNAs were constructed using the TreeView software. A total of 731 differentially and significantly expressed mRNAs were observed when GDM patients were compared to controls. Molecular functions and biological pathways, as analyzed by the DAVID database, identified 130 biological processes and nine signaling pathways ( P
Molecular Biology Reports, 2013
We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diab... more We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.
Revista de Saúde Pública, 2005
OBJETIVO: Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes d... more OBJETIVO: Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes de lesões dermatológicas em pacientes diabéticos. Assim, o objetivo do estudo foi investigar a presença de lesões cutâneas, não referidas pelo paciente diabético e sua relação com o controle metabólico da doença. MÉTODOS: Foram examinados 403 pacientes, dos quais 31% eram diabéticos do tipo 1 e 69% do tipo 2. Em ambulatório de um hospital universitário, os pacientes foram atendidos por endocrinologista para a avaliação endócrino-metabólica e por dermatologista para a avaliação dermatológica. O grau de controle metabólico foi documentado em 136 pacientes por meio da dosagem de hemoglobina glicada. RESULTADOS: Houve predomínio de dermatofitoses (82,6%), seguido de grupo de dermatoses como acne e degeneração actínica (66,7%), piodermites (5%), tumores cutâneos (3%) e necrobiose lipoídica (1%). Entre as dermatoses mais comuns em diabéticos, foram confirmados com exame histológico: dois diagnó...
Medicina (Ribeirao Preto. Online), 2000
A associação entre diabetes mellitus do tipo I com os genes HLA de classe II está bem estabelecid... more A associação entre diabetes mellitus do tipo I com os genes HLA de classe II está bem estabelecida. Os genes podem ser diferentes de acordo com a etnia do grupo estudado. Neste estudo, foram tipificados os antígenos HLA de classe II em uma população brasileira de pacientes com diabetes do tipo I. Para tal, foram estudados 58 pacientes diabéticos e 102 indivíduos sadios, procedentes da mesma área geográfica e com etnia semelhante à dos pacientes. Os linfócitos B foram separados, utilizando-se lã de nylon. Os antígenos HLA foram tipificados por intermédio de um método de microlinfocitotoxicidade dependente de complemento. A análise estatística foi realizada pelo teste exato de Fisher bicaudal. As freqüências dos antígenos HLA-DR3 e HLA-DR4 e as combinações dos antígenos HLA-DR3 e DR4 estavam significantemente elevadas nos pacientes (P < 0,05). As freqüências dos antígenos HLA-DQ2 e HLA-DQ3 não foram significantemente diferentes daquelas observadas em controles, quando analisadas se...
Brazilian Journal of Medical and Biological Research, 2007
The objective of the present study was to evaluate the production of cytokines, interferon-γ (INF... more The objective of the present study was to evaluate the production of cytokines, interferon-γ (INF-γ) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-γ and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-γ levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-γ and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-γ and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.
Revista Brasileira de Ginecologia e Obstetrícia, 2003
Nutrition Research, 1993
... WITH TYPE II DIABETES RECEIVING A BRAZILIAN REGIONAL RICE AND BEAN DIETEmilia Addison1, Milto... more ... WITH TYPE II DIABETES RECEIVING A BRAZILIAN REGIONAL RICE AND BEAN DIETEmilia Addison1, Milton Cesar Foss2, Julieta ReQina Rebello ... been based on nitrogen balance studies (2-5). Most of theseinvestigations have been conducted on young healthy individuals ...
Jornal Brasileiro de Patologia e Medicina Laboratorial, 2003
Recebido em 30/08/02 Aceito para publicação em 03/10/02 Análise dos critérios diagnósticos dos di... more Recebido em 30/08/02 Aceito para publicação em 03/10/02 Análise dos critérios diagnósticos dos distúrbios do metabolismo de glicose e variáveis associadas à resistência insulínica Diagnostic criteria of the glucose metabolism disorders and variables associated to insulin resistence
Jornal de Pediatria, 2001
Objective: to evaluate the frequency of diabetes mellitus and glucose intolerance in patients wit... more Objective: to evaluate the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis treated at the Pediatric Gastroenterology Service of HC-FMRP-USP. Methods: a cross-sectional analytical study was conducted on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP-USP. Oral glucose tolerance tests (OGTT) were performed, with simultaneous determination of glycemia and insulinemia. Areas under the curve were obtained for glycemia (G) and insulinemia (I) and the I/G ratio was calculated and correlated with the duration of clinical manifestation and pancreatic exocrine function. Results: five patients presented alterations: one was diabetic and four had glucose intolerance and/or hyperinsulinemia. There was a direct correlation between the area under the curve for insulinemia and the duration of mucoviscidosis. A significant inverse correlation was also observed between the area under the curve for insulinemia and I/G ratio, and number of enzyme capsules/kg/day. Conclusions: the frequency of alterations in glucose homeostasis observed in patients with mucoviscidosis was higher than in the population at large (20% of the total sample and 33% of the group of patients with glycemia and insulinemia on OGTT). Therefore, it is important that glucose tolerance tests be performed systematically in patients with mucoviscidosis so that metabolic abnormalities can be early detected, and proper treatment can be initiated.
It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the pre... more It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulindependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (GawNL) induced by aerosol administration of atropine sulfate. In all ofthe patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p<O.O5) in group D-2 (2.48 ± 0.12 s'4cPa' [mean±SEJ) than in group D-1 (2.11±0.10 s'-kPa'). Aerosol atropine caused a significant increase (p<0.001) in airway caliber in all three groups; however, the increase in GaW/VL was significantly lower in group D-2 (0.26±0.05 s"kPa 9 when compared with group D-1 (0.63±0.09 s'4cPa'; p<0.01)and group C(O.67±0.06 s'1cPa'; p<O.OOl). A weak but significant (p<O.02) ourrelation was observed between the increases in GaWIVL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared
Brazilian Journal of Medical and Biological Research, 2006
The increase in non-communicable chronic diseases of adults is due to demographic changes and cha... more The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with α = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.
Maturitas, 2008
Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans... more Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in young women (Group Y = 30.9 years, N = 7) and in women in late menopause (Group M = 64.7 years, N = 7) and their relationship to bone mineral density. Methods: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2 h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine as well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). Results: The aged patients presented lower femoral BMD (Y = 0.860 g/cm 2 vs. M = 0.690 g/cm 2 , p < 0.01), with four of them having a T score lower than −2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak = 236 pg/ml) than for subjects with osteoporosis (OM: peak = 134.4 pg/ml). Conclusions: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause.
Hormone and Metabolic Research, 2006
The present study was designed to determine the effects of metformin on the forearm glucose uptak... more The present study was designed to determine the effects of metformin on the forearm glucose uptake and blood flow after an oral glucose challenge. Eleven normal subjects, and ten non-obese type 2 diabetes patients without medication of anti-hyperglycemic drug and with medication of metformin for four weeks, were studied after an overnight fast (12-14 h) and 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique combined with indirect calorimetry. The forearm glucose uptake increased in diabetes patients taking metformin (63.5+/-9.1 VS. 39.1+/-5.3 mg/100 ml FA. 3 h). The increase of forearm glucose uptake was due to increase of blood flow. The glucose oxidation was greater in the group treated with metformin, compared to the same group without anti-hyperglycemic drug (19.3+/-2.6 VS. 7.7+/-2.6 mg/100 ml FA. 3 hrs). The free fatty acids were higher in diabetes patients, which normalized after taking metformin. In conclusion, it was found that in these participants metformin acts in insulin resistance; it increases glucose muscle uptake and blood flow. The enhancement of blood flow and lower free fatty acids, not described yet, could be direct effects of the drug or due to reduced glucose toxicity. These positive effects must be responsible for the improvement in vascular function.
Hormone and Metabolic Research, 1998
Phosphate is an active participant in energy metabolism, and its deficiency has been associated w... more Phosphate is an active participant in energy metabolism, and its deficiency has been associated with changes in insulin sensitivity and glucose tolerance. In the present study, we have investigated insulin secretion and glucose tolerance in individuals with moderate and acute phosphate deprivation and in patients with chronic hypophosphatemia. The individuals with dietary phosphate deprivation, evidenced by a significant reduction in phosphaturia from 232.3 +/- 37.1 to 56.8 +/- 23.9 mmol/24 hours, but with normal serum levels of inorganic phosphorus, presented circulating glucose and insulin levels similar to those of the pre-dietary period during the oral and intravenous glucose tolerance tests. In contrast, patients with chronic hypophosphatemia (inorganic phosphorus < 0.65 mmol/l) presented in hyperinsulinemia during the postabsorptive state and during the early and late phases of insulin secretion after the oral and intravenous glucose stimulus. The physiological response of a fall in serum phosphate after glucose administration observed in individuals with chronic hypophosphatemia was similar to that of normal individuals. The presence of hyperinsulinemia both basally and after glucose stimulation, with normal glycemia, in phosphate-depleted individuals suggests that this condition is associated with reduced insulin sensitivity. However, severe phosphate deprivation is necessary for the manifestation of this undesirable association. The deviation of phosphate to the intracellular medium occurring after glucose administration in hypophosphatemic individuals is similar to that of normal individuals and explains the occurrence of severe hypophosphatemia in malnourished hypophosphatemic individuals when submitted to parenteral refeeding.
Hormone and Metabolic Research, 1988
The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investig... more The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investigated in seven patients with untreated Cushing's disease, six patients with Addison's disease and four control subjects. Naloxone had no effects on ACTH hypersecretion or normal ACTH levels. These data confirm that naloxone cannot provide additional diagnostic or therapeutic approaches in ACTH hypersecretion syndromes, mainly in Cushing's disease. The mean percentage LH levels did not significantly change during low dose naloxone in controls or patients with Cushing's and Addison's diseases. This suggests that increased endogenous opioid peptides in these diseases may not modify the LH responses to low dose of naloxone. However, since three of five adults with Cushing's disease had increased LH levels during naloxone, further studies may be indicated.
Hormone and Metabolic Research, 1992
The present study was designed to determine forearm muscle glucose uptake and oxidation during th... more The present study was designed to determine forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge in patients with type A insulin resistance and acanthosis nigricans. Nine normal subjects and six acanthotic patients were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry in forearm. Two patients (1 and 6) with insulin resistance and acanthosis nigricans had impaired glucose tolerance. All other patients and normals revealed normal glucose tolerance during the tests. Decreased forearm muscle glucose uptake was observed in patients 1 and 6 compared to normal subjects (6.3 and 51.1 vs 127.7 +/- 10.1 mg/100 ml forearm.3 h, respectively). Decreased forearm muscle glucose oxidation was also observed in patient 1 as well as in patient 3 who showed normal glucose tolerance. Serum FFA levels were elevated in patient 1 but not in patient 3 and in the other acanthotic patients compared to the normal subjects. Serum insulin levels were significantly higher in acanthotic patients than in normals before and after glucose loading. The results of the present study revealed that two of six patients with type A insulin resistance and acanthosis nigricans who exhibited glucose intolerance also showed a decrease in peripheral muscle glucose uptake and nonoxidative glucose metabolism. Another patient (3) with normal glucose tolerance showed impaired muscle glucose oxidation but unaltered muscle glucose uptake and nonoxidative metabolism during the 3 hours of study.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Biomedical Materials Research Part A, 2011
We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalize... more We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalized with osteopontin (OPN) in a matrix of poly‐D,L‐lactic‐acid (PDLLA). In a canine endosseus 0.75‐mm gap implant model, we tested the osteointegrative impact of the OPN functionalized composite as an implant coating, and a non‐functionalized composite was used as reference control. During the four weeks of observation, the OPN functionalized composite coating significantly increased the formation of new bone in the porosities of the implant, but no differences were observed in the gap. The study provides evidence of its potential use either alone or in combination with other osteoconductive compounds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 94–101, 2011.
Medicine & Science in Sports & Exercise, 1981
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
ABSTRACT Background: Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destr... more ABSTRACT Background: Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic beta cells, which are responsible for insulin-producing. Type 2 diabetes (T2D) is a phenotypic and genetically heterogeneous chronic disease characterized by insulin resistance and deficient beta-cell function, being the most prevalent type of diabetes, accounts for 90% of all cases of diabetes. The standard definition of gestational diabetes mellitus (GDM) is the abnormal glucose metabolism diagnosed during pregnancy. Although these three types of diabetes are clinically well defined and T1D is the type more associated to the genetic background, little is known on the genetic contribution to T2D or GDM. Objectives: To compare/contrast the transcriptome profiling of peripheral blood mononuclear cells (PBMC) from patients presenting T1D, T2D or GDM by using the microarray technology allowing identifying the common or the exclusive differentially expressed genes, which characterize the three types of DM. Methods: One-color Agilent 4x44K whole functional genome microarray hybridizations of samples from T1D (n=19), T2D (n=20) or GDM (n=17) patients were quantified and data analyzed using bioinformatics pipeline included in the GeneSpring GX11 pack (Agilent). Cluster-TreeView algorithm was used to average hierarchical clustering of genes using Pearson uncentered metrics. Finally, DAVID functional analysis tool was used to analyze the functional clusters of interest. Results: Differentially expressed genes between patients of three types of diabetes were identified and classified according to: (i) association with biological regulation, immune response and insulin gene cluster (Venn diagram); (ii) DAVID functional clusters categories: T1D (INS, IGF2, HLA-G, HLA-E and GAD1), T2D (SOCS1, SOCS2, SOCS3, SOCS4, IGF2 and INS) and a third cluster identified by GOTERM_BP_FATIGO: response to corticosteroid stimulus and GO:0051384~response to glucocorticoid stimulus (GHR, TRH, FOS, CCND1 and HSD11B2). Conclusion: i) PBMC were adequate for the use as reporter cells to analyze the transcriptome profiling in DM, ii) although the three types of DM may present distinct etiopathogenic mechanisms, they exhibit shared modulated immune response and metabolism response genes, suggesting common pathways in the pathophysiology. Support: FAPESP, CNPq and CAPES (Brazil).
Human Immunology, 2014
Gestational diabetes mellitus (GDM) is the most common metabolic disorder observed during pregnan... more Gestational diabetes mellitus (GDM) is the most common metabolic disorder observed during pregnancy, and has been defined as an abnormal glucose metabolism first diagnosed during gestation. GDM women usually present postpartum diabetes, insulin resistance, metabolic syndrome, hypertension and dyslipidemia. Although few genetic markers have been described for GDM, approximately 10% of GDM patients present high probability of progression to type 1 diabetes (T1D). In a previous meta-analysis study, evaluating the transcript profiles of patients with the major types of diabetes, we reported that transcription profile of T1D patients was closer to GDM than to type 2 diabetes. Additionally, it has already been reported association of some HLA alleles with GDM, suggesting a possible immunological feature for GDM. In this study, we compared the transcription profiling of PBMCs of 18 GDM patients and 10 healthy pregnant women. Total RNA samples were hybridized to Agilent® 4 × 44 K oligo microarrays encompassing the whole human functional genome. Differentially expressed mRNAs were obtained by Rank Products analysis, which classifies transcripts according to their fold change values. The hierarchical clustering of mRNAs and samples were performed using the Cluster program, dendrograms and spatial representations of mRNAs were constructed using the TreeView software. A total of 731 differentially and significantly expressed mRNAs were observed when GDM patients were compared to controls. Molecular functions and biological pathways, as analyzed by the DAVID database, identified 130 biological processes and nine signaling pathways ( P
Molecular Biology Reports, 2013
We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diab... more We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.
Revista de Saúde Pública, 2005
OBJETIVO: Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes d... more OBJETIVO: Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes de lesões dermatológicas em pacientes diabéticos. Assim, o objetivo do estudo foi investigar a presença de lesões cutâneas, não referidas pelo paciente diabético e sua relação com o controle metabólico da doença. MÉTODOS: Foram examinados 403 pacientes, dos quais 31% eram diabéticos do tipo 1 e 69% do tipo 2. Em ambulatório de um hospital universitário, os pacientes foram atendidos por endocrinologista para a avaliação endócrino-metabólica e por dermatologista para a avaliação dermatológica. O grau de controle metabólico foi documentado em 136 pacientes por meio da dosagem de hemoglobina glicada. RESULTADOS: Houve predomínio de dermatofitoses (82,6%), seguido de grupo de dermatoses como acne e degeneração actínica (66,7%), piodermites (5%), tumores cutâneos (3%) e necrobiose lipoídica (1%). Entre as dermatoses mais comuns em diabéticos, foram confirmados com exame histológico: dois diagnó...
Medicina (Ribeirao Preto. Online), 2000
A associação entre diabetes mellitus do tipo I com os genes HLA de classe II está bem estabelecid... more A associação entre diabetes mellitus do tipo I com os genes HLA de classe II está bem estabelecida. Os genes podem ser diferentes de acordo com a etnia do grupo estudado. Neste estudo, foram tipificados os antígenos HLA de classe II em uma população brasileira de pacientes com diabetes do tipo I. Para tal, foram estudados 58 pacientes diabéticos e 102 indivíduos sadios, procedentes da mesma área geográfica e com etnia semelhante à dos pacientes. Os linfócitos B foram separados, utilizando-se lã de nylon. Os antígenos HLA foram tipificados por intermédio de um método de microlinfocitotoxicidade dependente de complemento. A análise estatística foi realizada pelo teste exato de Fisher bicaudal. As freqüências dos antígenos HLA-DR3 e HLA-DR4 e as combinações dos antígenos HLA-DR3 e DR4 estavam significantemente elevadas nos pacientes (P < 0,05). As freqüências dos antígenos HLA-DQ2 e HLA-DQ3 não foram significantemente diferentes daquelas observadas em controles, quando analisadas se...
Brazilian Journal of Medical and Biological Research, 2007
The objective of the present study was to evaluate the production of cytokines, interferon-γ (INF... more The objective of the present study was to evaluate the production of cytokines, interferon-γ (INF-γ) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-γ and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-γ levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-γ and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-γ and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.
Revista Brasileira de Ginecologia e Obstetrícia, 2003
Nutrition Research, 1993
... WITH TYPE II DIABETES RECEIVING A BRAZILIAN REGIONAL RICE AND BEAN DIETEmilia Addison1, Milto... more ... WITH TYPE II DIABETES RECEIVING A BRAZILIAN REGIONAL RICE AND BEAN DIETEmilia Addison1, Milton Cesar Foss2, Julieta ReQina Rebello ... been based on nitrogen balance studies (2-5). Most of theseinvestigations have been conducted on young healthy individuals ...
Jornal Brasileiro de Patologia e Medicina Laboratorial, 2003
Recebido em 30/08/02 Aceito para publicação em 03/10/02 Análise dos critérios diagnósticos dos di... more Recebido em 30/08/02 Aceito para publicação em 03/10/02 Análise dos critérios diagnósticos dos distúrbios do metabolismo de glicose e variáveis associadas à resistência insulínica Diagnostic criteria of the glucose metabolism disorders and variables associated to insulin resistence
Jornal de Pediatria, 2001
Objective: to evaluate the frequency of diabetes mellitus and glucose intolerance in patients wit... more Objective: to evaluate the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis treated at the Pediatric Gastroenterology Service of HC-FMRP-USP. Methods: a cross-sectional analytical study was conducted on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP-USP. Oral glucose tolerance tests (OGTT) were performed, with simultaneous determination of glycemia and insulinemia. Areas under the curve were obtained for glycemia (G) and insulinemia (I) and the I/G ratio was calculated and correlated with the duration of clinical manifestation and pancreatic exocrine function. Results: five patients presented alterations: one was diabetic and four had glucose intolerance and/or hyperinsulinemia. There was a direct correlation between the area under the curve for insulinemia and the duration of mucoviscidosis. A significant inverse correlation was also observed between the area under the curve for insulinemia and I/G ratio, and number of enzyme capsules/kg/day. Conclusions: the frequency of alterations in glucose homeostasis observed in patients with mucoviscidosis was higher than in the population at large (20% of the total sample and 33% of the group of patients with glycemia and insulinemia on OGTT). Therefore, it is important that glucose tolerance tests be performed systematically in patients with mucoviscidosis so that metabolic abnormalities can be early detected, and proper treatment can be initiated.
It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the pre... more It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulindependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (GawNL) induced by aerosol administration of atropine sulfate. In all ofthe patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p<O.O5) in group D-2 (2.48 ± 0.12 s'4cPa' [mean±SEJ) than in group D-1 (2.11±0.10 s'-kPa'). Aerosol atropine caused a significant increase (p<0.001) in airway caliber in all three groups; however, the increase in GaW/VL was significantly lower in group D-2 (0.26±0.05 s"kPa 9 when compared with group D-1 (0.63±0.09 s'4cPa'; p<0.01)and group C(O.67±0.06 s'1cPa'; p<O.OOl). A weak but significant (p<O.02) ourrelation was observed between the increases in GaWIVL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared
Brazilian Journal of Medical and Biological Research, 2006
The increase in non-communicable chronic diseases of adults is due to demographic changes and cha... more The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with α = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.
Maturitas, 2008
Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans... more Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in young women (Group Y = 30.9 years, N = 7) and in women in late menopause (Group M = 64.7 years, N = 7) and their relationship to bone mineral density. Methods: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2 h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine as well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). Results: The aged patients presented lower femoral BMD (Y = 0.860 g/cm 2 vs. M = 0.690 g/cm 2 , p < 0.01), with four of them having a T score lower than −2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak = 236 pg/ml) than for subjects with osteoporosis (OM: peak = 134.4 pg/ml). Conclusions: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause.
Hormone and Metabolic Research, 2006
The present study was designed to determine the effects of metformin on the forearm glucose uptak... more The present study was designed to determine the effects of metformin on the forearm glucose uptake and blood flow after an oral glucose challenge. Eleven normal subjects, and ten non-obese type 2 diabetes patients without medication of anti-hyperglycemic drug and with medication of metformin for four weeks, were studied after an overnight fast (12-14 h) and 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique combined with indirect calorimetry. The forearm glucose uptake increased in diabetes patients taking metformin (63.5+/-9.1 VS. 39.1+/-5.3 mg/100 ml FA. 3 h). The increase of forearm glucose uptake was due to increase of blood flow. The glucose oxidation was greater in the group treated with metformin, compared to the same group without anti-hyperglycemic drug (19.3+/-2.6 VS. 7.7+/-2.6 mg/100 ml FA. 3 hrs). The free fatty acids were higher in diabetes patients, which normalized after taking metformin. In conclusion, it was found that in these participants metformin acts in insulin resistance; it increases glucose muscle uptake and blood flow. The enhancement of blood flow and lower free fatty acids, not described yet, could be direct effects of the drug or due to reduced glucose toxicity. These positive effects must be responsible for the improvement in vascular function.
Hormone and Metabolic Research, 1998
Phosphate is an active participant in energy metabolism, and its deficiency has been associated w... more Phosphate is an active participant in energy metabolism, and its deficiency has been associated with changes in insulin sensitivity and glucose tolerance. In the present study, we have investigated insulin secretion and glucose tolerance in individuals with moderate and acute phosphate deprivation and in patients with chronic hypophosphatemia. The individuals with dietary phosphate deprivation, evidenced by a significant reduction in phosphaturia from 232.3 +/- 37.1 to 56.8 +/- 23.9 mmol/24 hours, but with normal serum levels of inorganic phosphorus, presented circulating glucose and insulin levels similar to those of the pre-dietary period during the oral and intravenous glucose tolerance tests. In contrast, patients with chronic hypophosphatemia (inorganic phosphorus < 0.65 mmol/l) presented in hyperinsulinemia during the postabsorptive state and during the early and late phases of insulin secretion after the oral and intravenous glucose stimulus. The physiological response of a fall in serum phosphate after glucose administration observed in individuals with chronic hypophosphatemia was similar to that of normal individuals. The presence of hyperinsulinemia both basally and after glucose stimulation, with normal glycemia, in phosphate-depleted individuals suggests that this condition is associated with reduced insulin sensitivity. However, severe phosphate deprivation is necessary for the manifestation of this undesirable association. The deviation of phosphate to the intracellular medium occurring after glucose administration in hypophosphatemic individuals is similar to that of normal individuals and explains the occurrence of severe hypophosphatemia in malnourished hypophosphatemic individuals when submitted to parenteral refeeding.
Hormone and Metabolic Research, 1988
The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investig... more The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investigated in seven patients with untreated Cushing's disease, six patients with Addison's disease and four control subjects. Naloxone had no effects on ACTH hypersecretion or normal ACTH levels. These data confirm that naloxone cannot provide additional diagnostic or therapeutic approaches in ACTH hypersecretion syndromes, mainly in Cushing's disease. The mean percentage LH levels did not significantly change during low dose naloxone in controls or patients with Cushing's and Addison's diseases. This suggests that increased endogenous opioid peptides in these diseases may not modify the LH responses to low dose of naloxone. However, since three of five adults with Cushing's disease had increased LH levels during naloxone, further studies may be indicated.
Hormone and Metabolic Research, 1992
The present study was designed to determine forearm muscle glucose uptake and oxidation during th... more The present study was designed to determine forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge in patients with type A insulin resistance and acanthosis nigricans. Nine normal subjects and six acanthotic patients were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry in forearm. Two patients (1 and 6) with insulin resistance and acanthosis nigricans had impaired glucose tolerance. All other patients and normals revealed normal glucose tolerance during the tests. Decreased forearm muscle glucose uptake was observed in patients 1 and 6 compared to normal subjects (6.3 and 51.1 vs 127.7 +/- 10.1 mg/100 ml forearm.3 h, respectively). Decreased forearm muscle glucose oxidation was also observed in patient 1 as well as in patient 3 who showed normal glucose tolerance. Serum FFA levels were elevated in patient 1 but not in patient 3 and in the other acanthotic patients compared to the normal subjects. Serum insulin levels were significantly higher in acanthotic patients than in normals before and after glucose loading. The results of the present study revealed that two of six patients with type A insulin resistance and acanthosis nigricans who exhibited glucose intolerance also showed a decrease in peripheral muscle glucose uptake and nonoxidative glucose metabolism. Another patient (3) with normal glucose tolerance showed impaired muscle glucose oxidation but unaltered muscle glucose uptake and nonoxidative metabolism during the 3 hours of study.(ABSTRACT TRUNCATED AT 250 WORDS)