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background Vitamin D deficiency in pregnancy has been associated with an increased risk of preeclampsia. However, the association between serum vitamin D and blood pressure in pregnant women has been scarcely evaluated, particularly in women with a high risk of developing hypertensive disorders of pregnancy. We sought to evaluate the association between serum 25-hydroxyvitamin D and blood pressure in pregnant women with gestational diabetes mellitus (GDM). methods A cohort of 184 pregnant women with GDM was followed during the third trimester of pregnancy and early puerperium. Blood pressure was recorded in all prenatal visits, and serum vitamin D was measured by chemiluminescence immunoassay. Pearson’s coefficients and multiple linear regressions were used to study predictors of blood pressure levels. results Women with vitamin D insufficiency (

Objectives: The aims of this study were to estimate the local rate of postpartum diabetes screening after gestational diabetes mellitus (GDM) pregnancies, and to identify clinical variables associated with retesting rates and with the persistence of decreased glucose tolerance. Subjects and methods: Prospective cohort of GDM women with prenatal delivery at a specialized center, from November 2009 to May 2012. All women were advised to schedule a 6 weeks postpartum 75-g oral glucose tolerance test (OGTT). Results: Of the 209 women included, 108 (51.7%) returned to be tested with fasting plasma glucose (n = 14), OGTT (n = 93) or random glucose (n = 1). Return was associated with lower parity rate (2 vs. 3, p < 0.001) and higher pregnancy 2-h OGTT (165 vs. 155 mg/dL, p = 0.034), but not with socio-demographic characteristics. Four women (3.7%) had diabetes, 22 (20.4%) had impaired fasting glucose or impaired glucose tolerance. Persistent hyperglycemia was associated with a positive family history of diabetes (relative risk - RR 2.41, p = 0.050), diagnostic 2-h OGTT in pregnancy (RR 1.01, p = 0.045), insulin use during pregnancy (RR 2.37, p = 0.014), and cesarean section (RR 2.61, p = 0.015). Conclusions: Even though postpartum abnormalities were frequent in GDM, rates of postpartum diabetes screening were undesirably low. As no specific clinical profile defines who will adhere to postpartum testing, it is essential to encourage all women to reevaluate their glucose status, particularly those with a family history of diabetes and more severe hyperglycemia. Arq Bras Endocrinol Metab. 2014;58(2):197-204 Objetivos: Os objetivos foram estimar a taxa de reavaliação de diabetes pós-parto em mulheres com diabetes melito gestacional (DMG) e identificar fatores associados ao retorno e à persistência das alterações glicêmicas. Sujeitos e métodos: Coorte prospectiva de mulheres com DMG atendidas em ambulatório de pré-natal especializado, de novembro de 2009 a maio de 2012. Todas foram orientadas a agendar o teste oral de tolerância à glicose (TOTG) a partir da sexta semana pós-parto. Resultados: Das 209 mulheres arroladas na gestação, 108 (51,7%) foram avaliadas após o parto: 14 com glicemia de jejum, 93 com o TOTG e uma com glicemia ao acaso. O retorno para reavaliação foi associado com menor paridade (2 vs. 3, p < 0,001) e com glicemia de 2-h mais elevada no TOTG diagnóstico (165 vs. 155 mg/dL, p = 0,034). Diabetes foi diagnosticado em quatro mulheres (3,7%) e pré-diabetes em 22 (20,4%). Análise multivariada evidenciou que a história familiar de diabetes (risco relativo – RR 2,41, p = 0,050), a glicemia de 2 horas no TOTG da gestação (RR 1,01, p = 0,045), o uso de insulina na gestação (RR 2,37, p = 0,014) e a taxa de cesariana (RR 2,61, p = 0,015) foram os fatores associados à persistência da hiperglicemia. Conclusões: O retorno para reavaliação foi baixo, embora as alterações glicêmicas tenham sido frequentes. Como não houve fatores que indiquem quais mulheres retornarão, estratégias para aumentar a adesão são necessárias, especialmente quando há história familiar ou o DMG foi mais grave. Arq Bras Endocrinol Metab. 2014;58(2):197-204

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation seems to correct the overdiagnosis of chronic kidney disease (CKD) provided by Modification of Diet in Renal Disease (MDRD) equation. However, this point has not been tested in some ethnic groups. This study investigated the performance of MDRD and CKD-EPI equations in South Brazilian individuals. Methods: This cross-sectional study included 354 individuals including healthy volunteers, diabetic and nondiabetic individuals with or without CKD. Glomerular filtration rate (GFR) was measured by the 51Cr-EDTA single- injection method (51Cr-GFR). Accuracy (P30), bias, and Bland-Altman agreement plots were evaluated. Results: In the group as a whole, 51Cr-GFR was 87 ± 37 (6-187), CKD-EPI eGFR, 82 ± 30 (6-152), and MDRD eGFR, 77 ± 28 (6-156) mL/min/1.73 m2 (p < 0.001 for all comparisons). Analyzing the subset of individuals with 51Cr-GFR < 60 mL/min/1.73 m2, P30 values were, respectively, 76% and 84% for MDRD and for CKD-EPI (p < 0.001) while for 51Cr-GFR ≥ 60 mL/min/1.73 m2, P30 values were 57.5% for both equations (p = 1.000). For MDRD and CKD-EPI, mean bias were negative for GFRs < 60 (–11 vs. –12, p = 0.221) and positive for values > 60 (16 vs. 9, p < 0.001). In multivariate analysis, absolute bias was unfavorably influenced by measured GFR > 60 (for MDRD) and being diabetic or younger (for CKD-EPI). Conclusions: CKD-EPI reduces GFR underestimation in individuals with GFRs > 60, but still presents a quite low accuracy at this GFR range. Moreover, it tends to overestimate GFR in subjects with GFRs < 60 mL/min/1.73 m2. CKD stages 1 and 2, diabetes and young age had a negative influence on the performance of the equations.

In the bone marrow, hematopoietic stem cells (HSCs) lodge in specialized microenvironments that tightly control the proliferative state of HSCs to adapt to the varying needs for replenishment of blood cells while also preventing HSC exhaustion. All putative niche cells suggested thus far have a nonhematopoietic origin. Thus, it remains unclear how feedback from mature cells is conveyed to HSCs to adjust their proliferation. Here we show that megakaryocytes (MKs) can directly regulate HSC pool size in mice. Three-dimensional whole-mount imaging revealed that endogenous HSCs are frequently located adjacent to MKs in a nonrandom fashion. Selective in vivo depletion of MKs resulted in specific loss of HSC quiescence and led to a marked expansion of functional HSCs. Gene expression analyses revealed that MKs are the source of chemokine C-X-C motif ligand 4 (CXCL4, also named platelet factor 4 or PF4) in the bone marrow, and we found that CXCL4 regulates HSC cell cycle activity. CXCL4 injection into mice resulted in a reduced number of HSCs because of their increased quiescence. By contrast, Cxcl4(-/-) mice exhibited an increased number of HSCs and increased HSC proliferation. Combined use of whole-mount imaging and computational modeling was highly suggestive of a megakaryocytic niche capable of independently influencing HSC maintenance by regulating quiescence. These results indicate that a terminally differentiated cell type derived from HSCs contributes to the HSC niche, directly regulating HSC behavior.

Hematopoietic stem cell (HSC) aging is accompanied by an expansion of myeloid-biased HSCs with declined long-term self-renewal functions, contributing to the development of hematologic malignancies. Recent studies have suggested a role for the bone marrow microenvironment in HSC aging but the extrinsic molecular mechanisms driving their aging remain largely unknown. Mesenchymal stem cells (MSCs) form a critical component of the HSC niche, promoting HSC quiescence and balanced differentiation. Some MSC activity is found associated with arterioles, which are densely innervated by the sympathetic nervous system (SNS). We used tridimensional whole-mount bone marrow confocal immunofluorescence imaging of HSCs and vascular structures to investigate the effects of aging on the HSC microenvironment. Comparative bone marrow analyses of aged (20-24 months) C57BL/6 and Nestin-GFP transgenic mice (where GFP marks MSCs) with young (2 month-old) C57BL/6 mice, revealed significant reductions in sympathetic innervation (3-fold, p Disclosures Frenette: Pfizer: Consultancy; GSK: Research Funding; PHD Biosciences: Research Funding.

Hematopoietic stem cells (HSCs) possess the ability to maintain the entire population of blood cells throughout life and to replenish the hematopoietic system after transplantation into marrow-ablated recipients. In mammalian adults, HSCs predominantly reside in the bone marrow to generate and maintain all blood cell types. HSCs, however, retain their ability to migrate to ectopic niches via the bloodstream, and traffic back to the bone marrow microenvironment via in part the interactions of alpha4 integrins with Vascular Cell Adhesion Molecule-1 (Vcam1, also known as CD106), constitutively expressed by endothelial and stromal cells. In the course of studies to investigate the role of Vcam1 in the macrophage erythroblastic niche, we have found using Vcam1-floxed mice crossed with a Csf1r-iCre (hereafter Vcam1Δ/Δ) that Vcam1 and Cre, using this transgenic line, were expressed on Lineage− (Lin−) c-Kit+ Sca1+ CD48− CD150+ HSCs. Although Vcam1Δ/Δ mice show no significant steady-state hematopoietic defect, transplantation of Vcam1Δ/Δ bone marrow, both in competitive and non-competitive settings, failed to engraft irradiated wild-type recipients. Indeed, ~80% of animals transplanted with Vcam1Δ/Δcells died, and the few that survived failed to successfully engraft secondary recipient mice. Vcam1Δ/Δ HSC/progenitors homed to bone marrow as well as wild-type counterparts and showed no detectable change in apoptosis in the bone marrow. However, syngeneic Vcam1Δ/Δ HSC/progenitors were selectively cleared in vivo by bone marrow macrophages over 4 days. The in vivo Vcam1Δ/Δ HSC/progenitor clearance did not require irradiation-induced damage since in steady-state parabiosis (Vcam1Δ/Δ and wild-type co-joined pairs), Vcam1Δ/Δ HSCs did not engraft the partner after G-CSF-induced mobilization whereas wild-type HSCs engrafted the parabiont partner. In addition, in vitro incubation of bone marrow-derived macrophages with Lin− cells revealed rapid phagocytosis by macrophages of Vcam1Δ/Δ, but not wild-type, cells and phagocytosis was also induced when the integrin alpha4 beta1 (also known as VLA-4) was blocked in wild-type Lin− cells. Thus, these results suggest that Vcam1 expressed on HSCs serves as a novel don't-eat-me signal, controlling the migration in the bone marrow by a macrophage-enabled checkpoint. Since we found that Vcam1 is expressed at higher levels on acute myelogenous leukemia (AML) cells than on healthy HSCs, and high VCAM1 expression correlates with poor prognosis in human AML patients (Ley et. al. NEJM 2013), we examined whether Vcam1 expression by AML cell could affect leukemogenesis in vivo. To test this idea, we generated AML-Vcam1Δ/Δand AML-Control cells by transduction of bone marrow Lin− c-Kit+ Sca1+ cells with the pMSCV-MLL-AF9-GFP oncogene. Strikingly, FACS analysis of primary AML recipient bone marrow revealed a marked reduction (>99%) in the number and percentage of phenotypic Lin− IL7Rα− Sca1− MLL-AF9 GFP+ c-Kithigh CD34low FcγRII/IIIhigh leukemic stem cells in AML-Vcam1Δ/Δmice compared to control. These results were confirmed by imaging analyses, which showed a marked reduction in leukemic infiltration in AML-Vcam1Δ/Δmice compared to control. Kaplan-Meier survival analysis of secondary recipient mice receiving 20,000 GFP+ leukemic cells revealed a significantly greater survival of mice harboring AML-Vcam1Δ/Δ cells relative to AML-Control (P50% circulating AML-GFP+ cells) with a daily injection of saline, IgG control, anti-Vcam1 blocking antibody (100 μg/day), cytarabine (100 mg/kg), or a combination of anti-Vcam1/cytarabine for 5 days. Remarkably, this short treatment with anti-Vcam1 blocking antibody was able to preferentially and significantly reduce the frequency and absolute number of phenotypic bone marrow leukemic stem cells in vivo. In addition, our results suggest that using a blocking anti-Vcam1 antibody synergizes with cytarabine treatment to decrease leukemic burden in vivo. These studies lay the groundwork for the development of a new therapeutic strategy for eliminating leukemia stem cells by modulating the innate immune response. Disclosures Frenette: GSK: Research Funding; Pfizer: Consultancy; PHD Biosciences: Research Funding.

Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Endocrinol Unit, Postgrad Fellowship Program Endocrinol, Porto Alegre, RS, Brazil

OBJECTIVE To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 ± 9 years; diabetes duration 8.5 ± 7 years), 17 SKN (2 men, age 57 ± 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 μg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 μg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 ± 21.4 ml · min−1 · 1.73 m−2) and SKD patients (73.0 ± 21.5 ml · min−1 · 1.73 m−2) were similar but higher than the one-kidney GFR (GFR ÷ 2) of the age-, sex-, and BMI-matched normal individuals (50.5 ± 9.0 ml · min−1 · 1.73 m−2) and normoalbuminuric type 2 diabetic patients (54.0 ± 11.6 ml · min−1 · 1.73 m−2). CONCLUSIONS Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.

A 36 year old man with a large goiter was suspected of having iodide (I − ) transport defect based on low thyroidal and salivary gland radioiodide uptake. Thyroid surgery was performed, because thyroid cytology could not exclude a malignancy. Sequencing of the entire Na + /I − symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide (nt) 1163 with an adenine, resulting in a stop (TGA) at codon 272. This nonsense mutation produces a truncated NIS with undetectable I − transport activity when expressed into COS-7 cells. Genotyping confirmed that the propositus was homozygous for the mutation whereas his unaffected mother, son, and paternal aunt were heterozygous. This nt substitution was not detected in any of 50 normal individuals, ruling out a polymorphism. While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterogygote (C272X) is sufficient to maintain active thyroidal I − uptake and function.

Aim To evaluate the influence of age of onset and duration of diabetes on the positivity of glutamic acid decarboxylase antibody (GADA) in South-Brazilian type 1 diabetes mellitus (DM) patients. Methods GADA was evaluated in 92 patients with type 1 diabetes, in 147 gestational DM patients, and in 59 subjects with normal glucose tolerance. Results Type 1 patients with positive GADA ( N = 44, 48%) were older at the onset of diabetes (22 ± 9 versus 18 ± 10 y, P = 0.043) and had a shorter DM duration (12 ± 8 versus 19 ± 9 y, P < 0.001), as compared with negative GADA patients. A logistic regression with antibody positivity as the dependent variable and diabetes duration as the independent variable, showed that the shorter diabetes duration was related to the presence of the antibody with an odds ratio (OR) = 5.6; (CI 95% = 2.1–14.6); P < 0.001. Another model, with age at diagnosis as the independent variable, did not show any association with antibody positivity. However, analysing only men, a shorter DM duration (OR = 6.5; CI = 1.7–24.0; P = 0.006), and also a higher age at diagnosis (OR = 5.5; CI = 1.5–21.0; P = 0.01) were significantly related to the antibody positivity. The performance of GADA was similar in up to 15 y of duration of DM ( P = 0.78), but significantly diminished with higher duration ( P = 0.001). Conclusion GADA testing is a helpful tool in the diagnosis of type 1 DM starting in young adults and older individuals. Even though the positivity rate declines along the course of disease, it still provides useful information up to 15 y after the diabetes diagnosis.

Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60 mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5 h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0 ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02 ng/mg, and the lower limits of quantification were 0.08 and 0.06 ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1.

OBJECTIVE To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS A longitudinal study of 32 normoalbuminuric (AER < 20 μg/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml · min−1 x 1.73 m−2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months. RESULTS There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (−0.61 ml · min−1.month−1; P = 0.001) than in NF (−0, 18) and control subjects (−0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 μg/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria. CONCLUSIONS The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).

Blood cell production is maintained throughout life by hematopoietic stem cells (HSC), which reside in specific areas of the bone marrow (BM) referred to as niches. These niches regulate the self-renewal, proliferation, and migration of HSC and also integrate signals from the periphery to respond to the hematopoietic demand. In the last decade, several putative cellular components of the HSC niche have been identified. Here, we briefly review current knowledge on different putative niche cells and their regulation.

The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals.Cross-sectional study conducted in 123 adult southern Brazilians with GFR60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method.Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P0.001). The difference between Jaffe creatinine and enzymatic creatinine was10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results.Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.

The development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20 mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65 °C overnight (~16 h) in order to extract the drugs of the matrix. Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25-10.00 ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02 ng/mg, and the limits of quantification were 0.03 and 0.06 ng/mg for cocaine and morphine, respectively. The proposed GC-EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative.

Introdução: a inflamação em baixo grau tem sido implicada na patogênese da nefropatia diabética e o uso de anti-inflamatórios poderia ser potencialmente útil como terapêutica. Objetivo: o objetivo deste estudo foi analisar o efeito de baixas doses de aspirina sobre a excreção urinária de albumina (EUA) e taxa de filtração glomerular (TFG) de pacientes com diabete melito (DM) tipo 2 microalbuminúricos. Métodos: neste estudo randomizado, duplo-cego, cruzado, controlado com placebo, 18 pacientes DM tipo 2 microalbuminúricos (EUA = 30-300 mg/24 h) receberam aspirina (300 mg / dia) ou placebo idêntico por 8 semanas, com um período de washout de 6 semanas. Os pacientes tinham idade de 56±9 anos, duração diabetes de 16±7,5 anos, 11 (61%) eram do sexo feminino, e todos estavam usando 20 mg de enalapril/dia. A TFG foi medida pelo 51Cr-EDTA e a EUA por imunoturbidimetria. O cálculo do tamanho da amostra: 17 pacientes para detectar uma alteração de 30% na EUA (α=0,05 e β=0,20). Resultados: após 8 semanas, não houve diferenças significativas entre placebo e aspirina, respectivamente, em relação à EUA [57,7 (8,9-420,0) vs. 63 (8,2-272,0) mg/24 h;P=0,45] e TFG (108±34 vs. 111±47 ml/min/1,73 m2; P=0,90). O controle glicêmico manteve-se estável. Os níveis de proteína C reativa [2,72 (0,34-10,3) vs. 2,03 (0,25-10,3) mg/l; P=0,21] foram semelhantes após placebo e aspirina, respectivamente. Não houve efeito de período (P=0,41) ou carry-over (P=0,49). Conclusão: a inflamação de baixo grau descrita na patogênese da nefropatia diabética não responde a baixas doses de aspirina. Background: low-grade inflammation has been implicated in the pathogenesis of diabetic nephropathy, and anti-inflammatory drugs could be potentially useful as a therapeutic tool. The aim of this study was to analyze the effect of low-dose aspirin (300 mg/d) on urinary albumin excretion (UAE) and glomerular filtration rate (GFR) levels of microalbuminuric type 2 DM patients. Methods: in this randomized, double-blind, crossover, placebo-controlled study, 18 microalbuminuric (UAE=30-300 mg/24 h) type 2 DM patients received aspirin (300 mg/d) or identical placebo for 8 weeks, with a 6-week washout period. The patients were aged 56±9 years, had a diabetes duration of 16±7.5 years; 11 (61%) were female, and they were all using enalapril 10 mg bid. GFR was measured by 51Cr-EDTA single-injection method and UAE by immunoturbidimetry. The sample-size calculation showed that 17 patients were needed to detect a 30% change in UAE (α= 0.05 and β= 0.20). Results: after 8 weeks of treatment, there were no significant differences between placebo and aspirin, respectively, regarding UAE [57.7 (8.9-420.0) vs. 63 (8.2-272.0) mg/24 h; P=0.45] and GFR (108±34 vs. 111±47 ml/min/1.73 m2; P=0.90). Glycemic control was stable throughout the C-reactive protein levels [2.72 (0.34-10.3) vs. 2.03 (0.25-10.3) μg/l; P=0.21] were comparable after placebo and aspirin, respectively. There were no period (P=0.41) or carry-over effects (P=0.49). Conclusion: low-dose aspirin did not affect GFR and UAE levels of microalbuminuric type 2 DM. It seems that the putative low-grade inflammation of diabetic nephropathy does not respond to these low doses of the drug.

In patients with Graves disease, unilateral or markedly asymmetric ocular manifestations should raise suspicion of other ocular disorders. In the present report, we describe a patient with Graves disease who presented with a 24-hour history of severe left-sided headache and fever. Cranial computed tomography revealed pansinusitis, and the patient was treated with antibiotics and discharged. He returned 24 hours later with worsening of the headache and left eye proptosis with retrobulbar pain, periorbital swelling, conjunctival redness, and chemosis. There was also external ophthalmoplegia on lateral, upward and downward gaze of the left eye. A diagnosis of Graves ophthalmopathy was made. Later, based on computed tomography of the orbit, which revealed frontal sinusitis and thrombosis of the left cavernous sinus, and on clinical and laboratory data, a diagnosis of thyroid storm with septic thrombosis of the cavernous sinus was made. To our knowledge, this is the first report of an association between a benign condition, sinusitis, and potentially lethal septic thrombosis of the cavernous sinus and thyroid storm. The presence of sinusitis in patients with Graves disease should alert physicians to the possibility of cavernous sinus thrombosis.

Several risk factors have been related to the development of diabetic nephropathy (DN) in type 2 diabetic patients, such as hyperglycemia, arterial hypertension, dyslipidemia, and smoking (1–5). Higher urinary albumin excretion rate (UAER) levels, even within the normal range, have been suggested to predict the development of DN in type 2 diabetic patients (1,2). Glomerular hyperfiltration has been investigated as a putative risk factor with conflicting results (6,7). The aim of this study was to analyze risk factors for micro- and macroalbuminuria in a cohort of 52 normoalbuminuric type 2 diabetic patients (UAER

O tratamento do diabetes gestacional é importante para evitar a morbimortalidade materno-fetal. O objetivo deste artigo é descrever o tratamento atualmente disponível para o manejo otimizado da hiperglicemia na gestação e sugerir um algoritmo de tratamento multidisciplinar. A terapia nutricional é a primeira opção de tratamento para as gestantes, e a prática de exercício físico leve a moderado deve ser estimulada na ausência de contraindicações obstétricas. O tratamento medicamentoso está recomendado quando os alvos glicêmicos não são atingidos ou na presença de crescimento fetal excessivo à ultrassonografia. O tratamento tradicional do diabetes gestacional é a insulinoterapia, embora mais recentemente a metformina venha sendo considerada uma opção segura e eficaz. A monitorização do tratamento é realizada com aferição da glicemia capilar e com avaliação da circunferência abdominal fetal por meio de ultrassonografia obstétrica a partir da 28ª semana de gestação. Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.

Serum creatinine measurement is a mainstay in the routine laboratory evaluation of renal function, despite of having several disadvantages. Cystatin C, on the other hand, suffers less influence of gender and muscle mass and has been proposed as a more sensitive marker for glomerular filtration rate. However, serum endogenous markers should not be used alone to assess glomerular filtration rate. Creatinine-based equations such as the modification of diet in renal disease (MDRD) and Cockcroft-Gault are widely used despite their limitations. A large number of cystatin C-based prediction equations were developed in recent years, in diverse populations, with different laboratory assays and methods. Several studies demonstrated that cystatin C-based equations are reliable markers of glomerular filtration rate and can be used for diagnosis, evaluation and follow-up of kidney disease. They are simpler than creatinine-based equations and have at least the same accuracy and precision for glomerular filtration rate estimation. In conclusion, diabetes mellitus, cystic fibrosis, kidney transplantation, HIV-infection, and cirrhosis are clinical situations where cystatin C-based equations can be useful. Extremes of age such as childhood and advanced age have also been evaluated with favorable results.

A nefropatia diabética (ND) é uma complicação crônica grave do diabetes melito (DM); é a principal causa de insuficiência renal terminal. A ND é classificada em 3 estágios conforme a excreção urinária de albumina (EUA): normoalbuminúria (EUA 174 mg/l). Da fase de microalbuminúria pode ocorrer regressão para normoalbuminúria (30% casos) ou progressão para a macroalbuminúria, quando ocorre maior risco de evo- lução para a doença renal crônica (DRC) terminal. O diagnóstico da ND é realizado através da medida da albumina na urina e pela avaliação da taxa de filtração glomerular (TFG). Recomenda-se a medida da albumina em amostra isolada de urina (primeira da manhã ou amostra casual), podendo-se medir o índice albumina-creatinina ou a concentração de albumina. Valores elevados de albuminúria devem ser confirmados em pelo menos 2 de 3 coletas de urina, em um intervalo de 3 a 6 meses. Na impossibilidade da medida da albuminúria, a medida de proteínas totais (proteinúria @430 mg/l em amostra ou >500 mg/24 h), pode ser utilizada para diagnóstico de fases mais avançadas de ND. Em pacientes com DM tipo 2 o rastre- amento deve iniciar ao diagnóstico de DM, e nos pacientes com DM tipo 1 deve ser após os 10 anos de idade; logo após o início da puberdade; ou quando a duração do DM for >5 anos. Se negativo repetir anualmente; e, se positivo, recomenda-se a monitoração mais frequente da albumina urinária A estimativa da TFG é realizada através de fórmulas que empregam a creatinina sérica, ajustadas para idade, gênero e etnia. São recomendadas as equações do estudo Modification of Diet in Renal Disease (MDRD) e Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Deve ser levado em conta que, em pacientes com DM, essas equações tendem a subestimar a TFG. A ND deve ser identificada o mais precocemente pos- sível e para isto tanto os profissionais de saúde como os pacientes com DM devem ser enfaticamente conscientizados. Diabetic nephropathy (DN) is an important chronic complication of diabetes mellitus (DM) and is the leading cause of end- staage renal disease. DN is classified into stages according to the urinary albumin excretion (UAE): normoalbuminuria (UAE 174 mg/l. From microalbuminuria there might be regression to normoalbuminuria (30% cases) or progression to macroalbuminuria, in which case there is higher risk of progression to advanced chronic kidney disease (CKD). DN has a high cardiovascular morbidity and mortality rate that is possibly more significant than the progression to terminal CKD. DN diagnosis is established by the measurement of albumin in the urine and assessment of glomerular filtration rate (GFR). The measurement of albumin in an isolated urine sample (first morning urine or random sample) is recommended, with the possibility of measuring albumin-creatinine ratio or albumin concentration. High levels of albuminuria should be confirmed by at least 2 out of 3 urine samples within a time interval of 3 to 6 months. If albuminuria cannot be measured, total protein level (proteinuria @ 430 mg/l in a sample or > 500 mg/24 h) can be used to diagnose advanced stages of DN. In patients with type 2 DM, screening should start upon diagnosis of DM, and in patients with type 1 DM, it should be started after the patient turns 10 years old; soon after the onset of puberty; or when the duration of DM is >5 years In case of negative results, screening should be repeated annually and, if the result is posi- tive, more frequent monitoring of urinary albumin is recommended. GFR estimation is calculated using formulas that employ serum creatinine adjusted for age, gender, and ethnicity. Modification of Diet in Renal Disease (MDRD) study and CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration) equations are the recommended. In patients with DM, this equation shows a tendency to underestimate GFR. In conclusion, DN should be identified as early as possible and with that purpose both health professionals and patients with DM should be educated on that issue.

A infecção do pé é uma importante causa de morbidade em pacientes com diabetes melito, sendo responsável pela maioria dos casos de amputação não traumática de membros inferiores. A ulceração, secundária principalmente à neuropatia diabética, deformidade e trauma, é o principal fator de risco para infecção. Prevenção e identificação precoce dessas alterações, com tratamento apropriado, constituem ferramentas essenciais para diminuir a morbidade relacionada. Neste artigo, relatamos o caso de um paciente com diabetes melito tipo 2 e infecção de pé diabético, com predominância de componente neuropático, e descrevemos o protocolo assistencial recomendado pelo Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre (HCPA). Infection of the foot is a major cause of morbity in patients with diabetes mellitus and is responsible for most cases of nontraumatic amputation of lower limbs. The ulceration, mainly secondary to diabetic neuropathy, deformity and trauma, is the main risk factor for infection. Prevention and early identification of these changes, along with its appropriate treatment are essential tasks to reduce morbidity related. We report a case of a patient with type 2 diabetes mellitus and infection of diabetic foot, mainly presenting neuropathy, and describe the protocol of care recommended by the Endocrinology Unit of the Hospital de Clínicas de Porto Alegre (HCPA).

Paciente do sexo feminino, 23 anos, cor preta, apresenta o diagnóstico de diabetes melito (DM) do tipo 1 desde os 7 anos de idade, com controle glicêmico persistentemente inadequado e inúmeras internações por cetoacidose diabética. Cursa com múltiplas complicações microvasculares relacionadas à doença, com diagnóstico de amaurose bilateral há 2 anos, secundária à retinopatia diabética, síndrome nefrótica e insuficiência renal crônica dialítica, gastroparesia diabética e síndrome de Mauriac (baixa estatura, atraso puberal, hepatomegalia e fácies cushingóide). Iniciou progressivamente com importante limitação dos movimentos das mãos, complicação também relacionada ao DM.

Introdução: O diabetes é complicação clínica frequente na gestação e sua prevalência vem aumentando nos últimos anos. Objetivo: Analisar a frequência dos tipos de diabetes na gestação, as características clínicas das gestantes e alguns desfechos materno-fetais, em pré-natal de alto risco. Método: Estudo retrospectivo de revisão dos prontuários eletrônicos de mulheres com diabetes e gestação atendidas no período de janeiro 2009 a junho 2010 no Hospital de Clínicas de Porto Alegre (HCPA). Resultados: Nesse período, 173 gestantes foram atendidas no ambulatório de gestação e diabetes, no total de 1459 consultas. O diabetes gestacional ocorreu em 84% das gestantes, 8% apresentaram diabetes tipo 2, 6%, diabetes tipo 1 e 2%, outros tipos. As mulheres com diabetes gestacional apresentaram HbA1c inferior às demais. A maioria das pacientes iniciou o pré-natal após o primeiro trimestre. A taxa geral de cesariana foi de 56%, tendo sido mais frequente no diabetes tipo 1. O recém-nascido foi considerado pequeno para a idade gestacional em 9% dos casos, e grande em 13%, sem diferença entre os tipos de diabetes. Nas mulheres com diabetes gestacional, o peso do recém-nascido correlacionou-se positivamente com o índice de massa corporal, glicemia de jejum ao diagnóstico e HbA1c da mãe. Conclusão: O diabetes associado à gestação é motivo frequente de atendimento no pré-natal especializado do HCPA, sendo a maioria diabetes gestacional. Nesses casos, obesidade e pior controle glicêmico associaram-se com o peso fetal aumentado. As gestantes chegam tardiamente ao centro de tratamento, com controle metabólico aquém do recomendado. Background: Gestational diabetes is a common complication of pregnancy and its prevalence has increased in the last years. Aim: To describe the frequency of different types of diabetes, maternal clinical characteristics, and pregnancy outcomes in pregnant diabetic women who received prenatal care at a high-risk prenatal center. Method: Review of medical records of pregnant diabetic women who received prenatal care between January 2009 and June 2010 at Hospital de Clínicas de Porto Alegre (HCPA). Results: In this period, 173 pregnant diabetic women received prenatal care; 1,459 medical visits were made. Gestational diabetes was diagnosed in 84% of the women, 8% had type 2 diabetes, 6% had type 1 diabetes, and 2% had other types of diabetes. Women with gestational diabetes had lower HbA1c than the other diabetic groups. Most patients started the prenatal care after the first quarter. The global frequency of cesarean section was 56% but it was more frequent among type 1 diabetics. Newborns were small for gestational age in 9% of the cases and large for gestational age in 13%, without significant differences between different types of diabetes. In gestational diabetic women, birth weight was associated with mother’s body mass index, fasting glycemia at diagnosis, and HbA1c. Conclusion: Diabetes associated with pregnancy is a frequent reason for prenatal care at HCPA; gestational diabetes is the most frequent type of diabetes and, in these women, maternal obesity and worst glycemic control adversely influenced fetal birth weight. Patients arrive with a suboptimal glycemic control and start their treatment with undesirable delay.

O diabetes melito tipo 2 (DM2) decorre de alteração na ação e secreção de insulina. A longo prazo, a elevação da glicemia promove dano microvascular, neuropatia e dano macrovascular, com consequente aumento da morbi-mortalidade destes pacientes. Nas últimas décadas, diversos ensaios clínicos clássicos demonstraram que intervenções terapêuticas específicas para corrigir a hiperglicemia e hipertensão arterial são capazes de prevenir ou retardar o avanço das complicações crônicas. Neste sentido, tratamento efetivo e da forma mais precoce possível deve ser oferecido a todos os pacientes com DM2. Fármacos antiobesidade e agentes orais, como a metformina, sulfonilureias, glinidas, tiazolidinedionas, inibidores da alfa-glicosidase, e os mais recentes fármacos incretinomiméticos e amilinomiméticos são apresentados nessa revisão, nos aspectos de mecanismos de ação, efeitos colaterais e contraindicações. Type 2 diabetes mellitus (DM2) is caused by changes in the action and secretion of insulin. In the long term, increased glucose levels promote microvascular damage, neuropathy, and macrovascular damage, leading to higher morbidity and mortality in these patients. In recent decades, several clinical trials have demonstrated that specific therapeutic interventions to correct hyperglycemia and hypertension are able to prevent or delay the advance of chronic complications. In this sense, effective and early treatment should be offered to all patients with DM2. Antiobesity drugs and oral agents, such as metformin, sulfonylureas, glinides, thiazolidinediones, alpha-glucosidase inhibitors, and the most recent drugs (incretin mimetics and amilin mimetics) are analyzed in the present review with regard to their mechanisms of action, side effects, and contraindications.

O tratamento do diabetes gestacional é importante para evitar a morbimortalidade materno- -fetal. O objetivo deste artigo é descrever o tratamento atualmente disponível para o manejo otimizado da hiperglicemia na gestação e sugerir um algoritmo de tratamento multidisciplinar. A terapia nutricional é a primeira opção de tratamento para as gestantes, e a prática de exercício físico leve a moderado deve ser estimulada na ausência de contraindicações obstétricas. O tratamento medicamentoso está recomendado quando os alvos glicêmicos não são atingidos ou na presença de crescimento fetal excessivo à ultrassonografia. O tratamento tradicional do diabetes gestacional é a insulinoterapia, embora mais recentemente a metformina venha sendo considerada uma opção segura e eficaz. A monitorização do tratamento é realizada com aferição da glicemia capilar e com avaliação da circunferência abdominal fetal por meio de ultrassonografia obstétrica a partir da 28a semana de gestação. Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.

O diabetes é caracterizado pelo aumento do nível de açúcar (glicose) no sangue (glicose maior do que 126 mg/dl). A glicose é a principal fonte de energia para as células do corpo, mas para poder ser utilizada é preciso a ação da insulina produzida pelo pâncreas. Quando o pâncreas não consegue produzir insulina suficiente ou essa insulina não funciona bem, a glicose no sangue aumenta causando o diabetes. No Brasil, aproximadamente 7% das pessoas tem diabetes. Os principais sintomas são aumento da sede, urinar grande quantidade várias vezes ao dia, fraqueza, emagrecimento, visão embaçada. No entanto, muitas pessoas não têm nenhum sintoma e podem nem saber que tem diabetes.

Paciente de 71 anos com diagnóstico de diabete melito tipo 2 desde os 63 anos, hipertenso, ex-tabagista e portador de doença arterial periférica, realizou cirurgia de revascularização fêmoro-poplítea em membro inferior direito aos 41 anos. Portador de nefropatia diabética clínica e retinopatia diabética proliferativa avançada. Apresentou lesão necrótica, sem secreção purulenta, em pequena área do primeiro pododáctilo do pé direito, a qual evoluiu lentamente de tamanho até envolver completamente o pododáctilo, sem relação com lesão traumática local (Figura). Durante a investigação evidenciou-se estenose de 50% do enxerto vascular do paciente, com pulsos pedioso e tibial posterior impalpáveis. Foi realizada amputação supracondiliana do membro inferior direito.

Esse volume da Revista HCPA aborda diversos aspectos relevantes do diabetes melito (DM). Os artigos apresentam o papel da HbA1c no diagnóstico, a descrição de tipos secundários de DM e do diabetes gestacional e as recomendações de prevenção e tratamento de algumas complicações crônicas, especialmente da nefropatia diabética e do pé diabético. Aborda também estratégias de tratamento que partem do manejo da hipertensão arterial e da hiperglicemia até a perspectiva próxima futura do transplante de ilhotas pancreáticas.

Objective— To evaluate the frequency and correlates of glomerular hyperfiltration in NIDDM patients without overt proteinuria. Research Design and Methods— A cross-sectional study was conducted. Seventy-one consecutive NIDDM patients attending an outpatient clinic, with Albustix-tested negative urine and a 24-h AER Results— GFR above the upper limit of the normal range for age-matched control subjects (137.1 ml·min−1 · 1.73 m2) was present in 15 of 71 (21%) NIDDM patients. Subjects with normal and hyperfiltration did not differ in terms of age, sex distribution, BMI, duration of NIDDM, BP, AER, or frequency of long-term complications. Plasma glucose was significantly higher in subjects with hyperfiltration (mean [range]: 12.8 [4.3–18.7] vs. 8.7 [2.6–17.5] mM). HbA1c failed to reach statistical significance, although it tended to be higher in the group with hyperfiltration (10.4 [6.7–13.9] vs. 9.4 [4.2–16.5]%, P = 0.10). Age (rS −0.37, P = 0.002), FPG (rS 0.45, P < 0.0005), total cholesterol (rS −0.31, P = 0.008), and glycosuria (rS 0.40, P = 0.001) correlated significantly with GFR. In a stepwise multiple regression analysis, FPG, age, and total cholesterol emerged as significant correlates of the dependent variable GFR. Conclusions— Hyperfiltration occurred in 21% of NIDDM patients without overt proteinuria. FPG and age significant correlates of the GFR in these patients. Cholesterol is significantly (although only modestly) correlated with the GFR.

Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.

International audience; Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, thetrophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra-embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst-derived stem cells and invivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development.

CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha signalling is responsible for the aberrant P-cadherin overexpression and for its role in inducing breast cancer cell invasion and migration. However, the mechanism by which ER-signalling inhibition leads to P-cadherin expression is still unknown. The aim of this study was to explore the molecular mechanism linking the ERalpha-signalling and P-cadherin-regulated expression in breast cancer cell lines. This study showed that ICI 182,780 is able to increase CDH3 promoter activity, inducing high levels of the active chromatin mark H3 lysine 4 dimethylation. We also observed, for the first time, that the transcription factor C/EBPbeta is able to up-regulate CDH3 promoter activity in breast cancer cells. Moreover, we showed that the expression of P-cadherin and C/EBPbeta are highly associated in human breast carcinomas and linked with a worse prognosis of breast cancer patients. This study demonstrates the existence of an epigenetic regulation by which ICI 182,780 up-regulates P-cadherin expression in MCF-7/AZ breast cancer cells through chromatin remodelling at CDH3 promoter, bringing forward the growing evidence that ERalpha signalling-abrogation by anti-oestrogens is able to induce the expression of ERalpha-repressed genes which, in the appropriate cell biology context, may contribute to a breast cancer cell invasion phenotype.CDH3 GenBank accession no. NT_010498.

A associação de hipertensão arterial sistêmica (HAS) e diabetes melito (DM) é bastante comum, acometendo mais de 60% dos pacientes com DM tipo 2. Os benefícios do tratamento da HAS nesses pacientes são bem definidos, entretanto há controvérsia em relação ao alvo de pressão a ser atingido nesses pacientes com o tratamento. O esquema terapêutico a ser utilizado deve levar em consideração não só o efeito dos medicamentos sobre a pressão arterial, mas também seus efeitos em mortalidade e complicações do DM. Na maior parte das recomendações nacionais e internacionais, os inibidores da enzima conversora da angiotensina são considerados drogas de primeira linha no tratamento desses pacientes, devido a seu efeito benéfico sobre a albuminúria, mas se discute o uso de diuréticos tiazídicos como terapia inicial, da mesma maneira que na população sem DM. Nessa revisão abordaremos as evidências em relação aos benefícios do tratamento da HAS em pacientes com DM, o alvo de pressão a ser atingido com esse tratamento e as vantagens e riscos do uso das diferentes classes de anti-hipertensivos nessa população. The association of hypertension and diabetes mellitus (DM) is quite common, affecting more than 60% of patients with type 2 DM. The benefits of treating hypertension in these patients are well defined, though there is controversy regarding the target pressure to be achieved in these patients. The regimen to be used should take into consideration not only the effect of medication on blood pressure, but also its effects on mortality and DM complications. In most national and international guidelines, angiotensin-converting enzyme inhibitors are considered first-line drugs in the treatment of these patients because of their beneficial effect on albuminuria, but the use of thiazide diuretics as initial therapy is controversial both in diabetic and non-diabetic populations. In the present review of the literature we discuss the evidence regarding the benefits of treating hypertension in diabetic patients, the target pressure to be achieved with this treatment, and the benefits and risks of using different classes of antihypertensive drugs in this population.

Introdução: Diferenças nos métodos de medida da creatinina sérica podem determinar amplas variações na taxa de filtração glomerular (TFG) estimada com fórmulas. Para a padronização da medida da creatinina, deve ser usado método calibrado rastreável para medida de referência com ID-MS (isotope dilution mass spectrometry). Objetivo: Avaliar a TFG estimada com a equação MDRD (Modification of Diet in Renal Disease) original (MDRDo, creatinina método não calibrado) e a equação MDRD re-expressa (MDRDr, método calibrado por ID-MS), comparando-as com a TFG medida pelo 51Cr-EDTA (método padrão) em indivíduos normais. Métodos: Foram avaliados 101 indivíduos, com idade média de 38±12 anos, sendo 45 homens. A TFG foi medida pela técnica de injeção única do 51Cr-EDTA (TFG 51Cr-EDTA) e estimada pelas equações MDRDo: 186xcreatinina sérica-1,154 x idade-0,203 x 0,742 (se mulher) x 1,210 (se negro) e MDRDr, substituindo-se o valor 186 por 175 na equação. A creatinina sérica foi medida pelo método de Jaffe não calibrado e transformada em calibrado com a fórmula: y=1,07x-0,249, obtida previamente por regressão. A concordância entre os métodos foi avaliada através da análise de Bland&Altman. Resultados: Os valores médios para as TFG 51Cr-EDTA, MDRDr e MDRDo foram de 105±18, 102±21 e 84±13 ml/min/1,73 m², respectivamente. Acurácia (percentual de casos de TFG estimada que não desviam em mais de 15% do valor medido) foi maior com o uso da MDRDr em relação à MDRDo (57% vs. 35%, P=0,002). O viés (diferença entre TFG medida e estimada) para 51Cr-EDTA e MDRDr foi de 3±23 ml/min/1,73 m². Para 51Cr-EDTA e MDRDo o viés foi significativamente maior, sendo de 21±18 ml/min/1,73 m². No entanto, a precisão, avaliada como desvio padrão do viés indicou elevada dispersão nos dois casos. Conclusão: O uso da equação re-expressa do MDRD, empregando a creatinina calibrada, produz uma estimativa mais acurada da TFG do que a equação original do MDRD. No entanto, devido à falta de precisão, ambas ainda são insatisfatórias para estimar a TFG. Background: Differences in methods of measurement of serum creatinine may provide wide variations in glomerular filtration rate (GFR) estimated with formulas. To standardize the measurement of creatinine, calibrated methods should be used, traceable to the reference ID-MS (isotope dilution mass spectrometry) method. Aim: To evaluate the performance of GFRs estimated with the original Modification of Diet in Renal Disease study equation (MDRDo; non-calibrated creatinine method) and with the re-expressed MDRD equation (MDRDr; ID-MS creatinine), comparing them with the GFR measured by 51Cr-EDTA (standard method ) in normal adults. Methods: 101 subjects, aged 38±12 years, 45 (45%) men were evaluated. GFR was measured by single-injection 51Cr- EDTA (GFR 51Cr-EDTA) technique and estimated by the following equations - MDRDo: 186 x serum creatinine-1. 154 x age-0. 203 x 0.742 (if female) x 1.210 (if black), and MDRDr, replacing the value 186 by 175 in the equation. Serum creatinine was measured by a non-calibrated Jaffe’s method and transformed into calibrated with the formula: y=1.07x-0.249, previously obtained by regression. The agreement between methods was assessed by the Bland&Altman analyses. Results: The mean GFR 51Cr-EDTA, MDRDr and MDRDo were 105±18, 102±21 and 84±13 ml/min/1, 73 m2, respectively. There was no agreement between 51Cr-EDTA and MDRDo GFR (P

Metástases de neoplasias para hipófise são incomuns e ocorrem em até 1% dos tumores de hipófise. Apresentamos o caso de um homem de 74 anos de idade com progressiva deterioração visual nos 30 dias que antecederam seu atendimento. Ele negava cefaleia ou poliúria e queixava- se de constipação intestinal. O paciente havia sido submetido à nefrectomia radical para carcinoma de células renais cinco anos antes, seguida de quimioterapia e radioterapia por metástases pulmonares e parotídea. Ao exame oftalmológico, apresentava paralisia do nervo abducente esquerdo e hemianopsia bitemporal. A ressonância magnética demonstrou uma massa selar com extensão suprasselar comprimindo o quiasma óptico. Na avaliação endocrinológica apresentava insuficiência adrenal e gonadal centrais. O paciente foi submetido à ressecção transesfenoidal da lesão que, ao exame anatomopatológico, se revelou como carcinoma de células renais. Esse caso demonstra que a presença de lesões metastáticas na hipófise pode mimetizar sinais e sintomas de macroadenoma não funcionante e que o diabetes insípido central, comum nas lesões metastáticas para hipófise, pode estar ausente. Metastatic tumors involving the pituitary gland are an uncommon finding and occur in up to 1% of all pituitary tumor resections. A 74-year-old man had progressive vision deterioration, over the 30 days prior to consultation. He did not complain of headache or polyuria, but referred to intestinal constipation. Five years ago, he underwent a right radical nephrectomy for renal cell carcinoma, followed by chemotherapy and radiotherapy for lung and parotid metastases. On ophthalmologic examination, there was a left abducens nerve palsy and bitemporal hemianopia. Magnetic resonance imaging demonstrated a sellar mass with suprasellar cistern extension compressing the optic chiasm. Endocrinological evaluation revealed central adrenal and gonadal insufficiencies. The patient underwent a transsphenoidal tumor resection that revealed renal cell carcinoma. This case illustrates that metastatic pituitary lesions can mimic typical symptoms and signs of pituitary macroadenoma. Furthermore, clinical diabetes insipidus, a common finding of pituitary metastases, can be absent.

Chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (GFR)

Objetivo. A prevalência das complicações crônicas do Diabetes mellitus (DM) é maior nos negros. A razão para esse achado é desconhecida. O objetivo desse estudo é analisar os fatores de risco para doença micro e macrovascular em pacientes com DM tipo 2 de acordo com a etnia. Métodos. Foi realizado estudo transversal avaliando 780 pacientes. Todos pacientes realizaram avaliação clinico/ laboratorial. A etnia foi autoreferida em branca (n = 585) ou negra (n = 195). Resultados. Os pacientes negros apresentaram níveis menores de triglicerídeos [115 (35-892) vs. 152 (34-1236) mg/dl; P

A hemocromatose é uma desordem caracterizada por armazenamento alterado de ferro. A forma adquirida da doença pode ser ocasionada por sobrecarga de ferro, alcoolismo, infecção pelo vírus da hepatite C, hepatite não-alcoólica e doença hepática crônica. A forma hereditária pode ser causada por diferentes mutações, sendo a C282Y e a H63D as mais freqüentes. A hemocromatose é uma patologia que pode acometer diferentes órgãos, entre eles: coração, articulações, fígado, hipotálamo, hipófise, gônadas e pâncreas. O objetivo deste estudo foi relatar um caso de hemocromatose e revisar a literatura, com especial atenção para a associação de hemocromatose e diabetes melito. Paciente 53 anos, masculino apresentou-se ao clínico geral com artralgias metacarpofalangeanas, tornozelos, joelhos, coxofemoral direita, lombar e cervical e queixas de astenia e emagrecimento. Entre 3 irmãos, um deles tinha diagnóstico de Hemocromatose Hereditária, com PCR demonstrando homozigose para C282Y. Trazia exames: TGO 128 U/L, TGP 231 U/L, fosfatase alcalina 258 U/L; ecografia abdominal com hepatomegalia e baço no limite superior da normalidade. Biópsia hepática demonstrou alargamento fibroso portal com hemossiderose intensa. Foi feito também o diagnóstico de diabetes melito A pesquisa da mutação confirmou a mesma mutação familiar: homozigose para C282Y, Hemochromatosis is a disorder characterized by iron storage amended. The acquired form of the disease can be caused by iron overload, alcoholism, infection by C virus hepatitis, non-alcoholic hepatitis and chronic liver disease. The hereditary form can be caused by different mutations, being the C282Y and H63D the most frequent, 83% of cases are homozigotous for C282Y and 4% are compound heterozygous (C282Y/H63D). Hemochromatosis is a condition that can affect several organs, including: heart, joints, liver, hypothalamus, pituitary, pancreas and gonads. The aim of this study was to report a case of hemochromatosis and review the literature, with special attention to the association of hemochromatosis and diabetes mellitus. Patient 53 years, male presented to the doctor with arthralgia metacarpophalangeal, ankles, knees, coxofemoral right, and cervical and lumbar, complaints of fatigue and weight loss. Between 3 brothers, one of them had a diagnosis of hereditary hemochromatosis, with PCR demonstrating homozygous for C282Y. Labs: GOT 128 U/L, ALT 231 U/L, alkaline phosphatase 258 U/L, abdominal ultrasound with hepatomegaly and spleen at the upper limit of normal. Liver biopsy demonstrated portal fibrosis extension with hemosiderosis intense. It also made the diagnosis of diabetes mellitus. The research confirmed the same mutation of the changing family: homozygous for C282Y