Use of Sensors in the Treatment and Follow-up of Patients with Diabetes Mellitus

Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable.

Hábitos y estilos de vida modificables en niños con sobrepeso y obesidad.

INTRODUCTION In the prevention for being overweight and for obesity, much attention is given to the influence of dietary factors, making the joint evaluation with other modifiable factors necessary. OBJECTIVES The aim of this project is to study the association between modifiable factors (physical activity, sedentary lifestyle, and dietary habits) with the prevalence of being overweight or obese in the youth population. METHODS Cross-Sectional study of 1283 school children between the ages of 3 and 16 years old, with measurements of the MBI, dietary habits, physical activity, sedentary lifestyle and family history of being overweight. Physical activity measured in MET was classified according to Pate criteria. RESULTS 22.4% of the boys and 32.9% of the girls were overweight. The presence of a BMI>25 in parents multiplied by 2.4 the risk of being overweight in children (OR CI 95% 1.5-3.7). 63.6% of overweight boys meet physical activity recommendations compared with 52.2% of girls, although in their case, it was greater than the average (45%). Sedentary time was 141 minutes for men and 128 minutes for women, with more sedentary behaviors associated with being overweight, especially in girls over 12 years of age (66.7%). Consuming cereal (OR 0.8) and having five meals per day (OR 0.5) act as protective factors. CONCLUSIONS In subjects with overweight, the levels of physical activity are close to those recommended levels, so which the values of a sedentary lifestyle together with dietary habits (if the parents have overweight) acquire a new relevance in intervention strategies of this problem.

Decrease in beta-Cell Proliferation Precedes Apoptosis during Diabetes Development in Bio-Breeding/Worcester Rat: Beneficial Role of Exendin-4

In autoimmune type 1 diabetes mellitus, proinflammatory cytokine-mediated apoptosis of beta-cells has been considered to be the first event directly responsible for beta-cell mass reduction. In the Bio-Breeding (BB) rat, an in vivo model used in the study of autoimmune diabetes, beta-cell apoptosis is observed from 9 wk of age and takes place after an insulitis period that begins at an earlier age. Previous studies by our group have shown an antiproliferative effect of proinflammatory cytokines on cultured beta-cells in Wistar rats, an effect that was partially reversed by Exendin-4, an analogue of glucagon-like peptide-1. In the current study, the changes in beta-cell apoptosis and proliferation during insulitis stage were also determined in pancreatic tissue sections in normal and thymectomized BB rats, as well as in Wistar rats of 5, 7, 9, and 11 wk of age. Although stable beta-cell proliferation in Wistar and thymectomized BB rats was observed along the course of the study, a decrease in beta-cell proliferation and beta-cell mass from the age of 5 wk, and prior to the commencement of apoptosis, was noted in BB rats. Exendin-4, in combination with anti-interferon-gamma antibody, induced a near-total recovery of beta-cell proliferation during the initial stages of insulitis. This highlights the importance of early intervention and, as well, the possibilities of new therapeutic approaches in preventing autoimmune diabetes by acting, initially, in the insulitis stage and, subsequently, on beta-cell regeneration and on beta-cell apoptosis.

Bone Mineral Density and Serum Levels of Soluble Tumor Necrosis Factors, Estradiol, and Osteoprotegerin in Postmenopausal Women with Cirrhosis after Viral Hepatitis

CONTEXT: Cirrhosis after viral hepatitis has been identified as a risk factor for osteoporosis in men. However, in postmenopausal women, most studies have evaluated the effect of primary biliary cirrhosis, but little is known about the effect of viral cirrhosis on bone mass [bone mineral density (BMD)] and bone metabolism. OBJECTIVE: Our objective was to assess the effect of viral cirrhosis on BMD and bone metabolism in postmenopausal women. DESIGN: We conducted a cross-sectional descriptive study. SETTING AND PATIENTS: We studied 84 postmenopausal female outpatients with viral cirrhosis and 96 healthy postmenopausal women from the general community. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN). RESULTS: The percentage with osteoporosis did not significantly differ between patients (LS, 43.1%; FN, 32.2%) and controls (LS, 41.2%; FN, 29.4%), and there was no difference in BMD (z-score) between groups. Serum concentrations of soluble TNF receptors, estradiol, and osteoprotegerin (OPG) were significantly higher in patients vs. controls (P < 0.001, P < 0.05, and P < 0.05, respectively). No significant difference was observed in urinary deoxypyridinoline. Serum OPG levels were positively correlated with soluble TNF receptors (r = 0.35; P < 0.02) and deoxypyridinoline (r = 0.37; P < 0.05). CONCLUSIONS: This study shows that bone mass and bone resorption rates do not differ between postmenopausal women with viral cirrhosis and healthy postmenopausal controls and suggests that viral cirrhosis does not appear to increase the risk of osteoporosis in these women. High serum estradiol and OPG concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.

A nutritional intervention study with hydrolyzed collagen in pre-pubertal Spanish children: influence on bone modeling biomarkers

Aim: The aim of the study was to investigate the influence of dietary intake of commercial hydrolyzed collagen (Gelatine Royal ®) on bone remodeling in pre-pubertal children. Methods: A randomized double-blind study was carried out in 60 children (9.42 ± 1.31 years) divided into three groups according to the amount of partially hydrolyzed collagen taken daily for 4 months: placebo (G-I, n = 18), collagen (G-II, n = 20) and collagen + calcium (G-III, n = 22) groups. Analyses of the following biochemical markers were carried out: total and bone alkaline phosphatase (tALP and bALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), type I collagen carboxy terminal telopeptide, lipids, calcium, 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone, free thyroxin and intact parathormone. Results: There was a significantly greater increase in serum IGF-1 in G-III than in G II (p < 0.01) or G-I (p < 0.05) during the study period, and a significantly greater increase in plasma tALP in G-III than in G-I (p < 0.05). Serum bALP behavior significantly (p < 0.05) differed between G-II (increase) and G-I (decrease). Plasma TRAP behavior significantly differed between G-II and G-I (p < 0.01) and between G-III and G-II (p < 0.05). Conclusion: Daily dietary intake of hydrolyzed collagen seems to have a potential role in enhancing bone remodeling at key stages of growth and development.

Residential Exposure to Outdoor Air Pollution during Pregnancy and Anthropometric Measures at Birth in a Multicenter Cohort in Spain

BACKGROUND. A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children's Health and Environment (INMA) mother and child cohort study. METHODS. Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. RESULTS. In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of -0.9 mm [95% confidence interval (CI), -1.8 to -0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (-0.16 mm; 95% CI, -0.27 to -0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, -45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. CONCLUSIONS. NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

INTRODUCTION Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children.

BACKGROUND Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION NFV is a safe drug with a good profile and able to achieve an adequate response in children.

Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy.

BACKGROUND Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults. METHODS HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) or=500 cells/microL at least during 6 months before the study and CD4+

Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak.

Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.

Acute oxygen sensing in heme oxygenase-2 null mice.

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K(+) channels and has been proposed to be the acute O(2) sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O(2) sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K(+) channel alpha-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K(+) channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O(2)-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K(+) channel gene expression but it does not alter the intrinsic O(2) sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O(2) sensor.

Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study

INTRODUCTION Higher and lower cerebral perfusion pressure (CPP) thresholds have been proposed to improve brain tissue oxygen pressure (PtiO2) and outcome. We study the distribution of hypoxic PtiO2 samples at different CPP thresholds, using prospective multimodality monitoring in patients with severe traumatic brain injury. METHODS This is a prospective observational study of 22 severely head injured patients admitted to a neurosurgical critical care unit from whom multimodality data was collected during standard management directed at improving intracranial pressure, CPP and PtiO2. Local PtiO2 was continuously measured in uninjured areas and snapshot samples were collected hourly and analyzed in relation to simultaneous CPP. Other variables that influence tissue oxygen availability, mainly arterial oxygen saturation, end tidal carbon dioxide, body temperature and effective hemoglobin, were also monitored to keep them stable in order to avoid non-ischemic hypoxia. RESULTS Our main results indicate that half of PtiO2 samples were at risk of hypoxia (defined by a PtiO2 equal to or less than 15 mmHg) when CPP was below 60 mmHg, and that this percentage decreased to 25% and 10% when CPP was between 60 and 70 mmHg and above 70 mmHg, respectively (p < 0.01). CONCLUSION Our study indicates that the risk of brain tissue hypoxia in severely head injured patients could be really high when CPP is below the normally recommended threshold of 60 mmHg, is still elevated when CPP is slightly over it, but decreases at CPP values above it.

Aseptic meningitis caused by Leptospira spp diagnosed by polymerase chain reaction

Leptospirosis is a zoonotic disease caused by the pathogenic Leptospira spp. The clinical presentations are diverse, ranging from undifferentiated fever to fulminant disease including meningeal forms. The neurological leptospirosis forms are usually neglected. The aim of this study was to investigate leptospirosis as the cause of aseptic meningitis using different diagnostic techniques including the polymerase chain reaction (PCR). Thirty-nine cerebrospinal fluid (CSF) samples from patients presenting with meningeal abnormalities, predominance of lymphocytes and negative results by traditional microbiological tests were processed by leptospiral culture, anti-leptospiral antibody response and PCR. Leptospira spp DNA was detected in 23 (58.97%) of the CSF samples. Anti-leptospiral antibodies were found in 13 (33.33%) CSF samples. Twelve CSF samples were positive by PCR assay and negative by microscopic agglutination test (MAT) assay. Two CSF samples were positive by MAT and negative by PCR. The positive and negative agreement between both tests was 11 and 14, respectively. CSF samples from six cases of unknown diagnosis were positive by PCR assay. Eight cases showed positive results using PCR and MAT. Leptospirosis could be detected by PCR assay from the 3rd-26th day after illness onset. The sensitivity of the PCR was assessed with confirmed cases of leptospirosis (by MAT) and found to be 89.5%. All CSFs were negative by culture. PCR was found to be a powerful tool for diagnosing meningitis cases of leptospirosis. We recommend that it may be used as a supplementary diagnostic tool, especially in the early stages of the disease, when other diagnostic techniques such as serology are not sensitive.