Correlation of Insulin Resistance with Anthropometric Measures and Blood Pressure in Adolescents

Abstract Background: Blood pressure is directly related to body mass index, and individuals with increased waist circumference have higher risk of developing hypertension, insulin resistance, and other metabolic changes, since adolescence. Objective: to evaluate the correlation of blood pressure with insulin resistance, waist circumference and body mass index in adolescents. Methods: Cross-section study on a representative sample of adolescent students. One group of adolescents with altered blood pressure detected by casual blood pressure and/or home blood pressure monitoring (blood pressure > 90th percentile) and one group of normotensive adolescents were studied. Body mass index, waist circumference were measured, and fasting glucose and plasma insulin levels were determined, using the HOMA-IR index to identify insulin resistance. Results: A total of 162 adolescents (35 with normal blood pressure and 127 with altered blood pressure) were studied; 61% (n = 99) of them were boys and the mean age was 14.9 ± 1.62 years. Thirty-eight (23.5%) adolescents had altered HOMA-IR. The group with altered blood pressure had higher values of waist circumference, body mass index and HOMA-IR (p<0.05). Waist circumference was higher among boys in both groups (p<0.05) and girls with altered blood pressure had higher HOMA-IR than boys (p<0.05). There was a significant moderate correlation between body mass index and HOMA-IR in the group with altered blood pressure (ρ = 0.394; p < 0.001), and such correlation was stronger than in the normotensive group. There was also a significant moderate correlation between waist circumference and HOMA-IR in both groups (ρ = 0.345; p < 0.05). Logistic regression showed that HOMA-IR was as predictor of altered blood pressure (odds ratio - OR = 2.0; p = 0.001). Conclusion: There was a significant association of insulin resistance with blood pressure and the impact of insulin resistance on blood pressure since childhood. The correlation and association between markers of cardiovascular diseases was more pronounced in adolescents with altered blood pressure, suggesting that primary prevention strategies for cardiovascular risk factors should be early implemented in childhood and adolescence.

Death caused by cardioinhibitory reflex cardiac arrest--a systematic review of cases.

Forensic pathologists often refer to the cardioinhibitory reflex cardiac arrest (CiRCA) following short neck trauma as a mechanism of death. We sought via a systematic review of the literature to identify circumstances under which carotid bifurcation stimulation could lead to death. Two independent reviewers selected case studies or reports from Medline, ISI Web of Knowledge, and Embase. Circumstances and contributory factors were extracted for each case. From the available data, authors independently assessed whether CiRCA was highly probable (no alternative explanation possible), probable (alternative explanation possible), or unlikely (alternative explanation highly probable). A narrative approach was used to define circumstances in which CiRCA remained possible. From the 48 published cases evoking CiRCA as a possible cause of death between 1881 and 2009, 28 were most likely to result of other mechanism of death (i.e., cerebral hypoxia due to carotid compression, mechanical asphyxia, myocardial infarction). CiRCA remained possible for 20 cases (including five based on anecdotal evidence only) with only one case with no alternative explanation other than CiRCA. Our findings support the presumption that reflex cardiac arrhythmia due to carotid bifurcation stimulation cannot provoke death alone. Actual state of knowledge suggests CiRCA might be contributory to death in the presence of drug abuse and/or cardiac pathology, often associated with physical and/or mental excitation.

Death Caused by Cardioinhibitory Reflex: What Experts Believe.

The danger of neck compression without restriction of the arterial flow remains unresolved in forensic medicine. There is an ongoing debate concerning life endangerment due to the cardioinhibitory reflex. The aim of this study was to determine what forensic medical experts believe and how they deal with this reflex. An anonymous electronic questionnaire was sent to 1429 forensic medical experts all over the world. We asked them about their opinion on the cardioinhibitory reflex, its role in causing death, and what their diagnostic criteria were.A total of 182 questionnaires were returned. The experts who answered were from 32 different countries. Our survey showed that 80.2% of experts believe that the cardioinhibitory reflex can theoretically cause death. In the practical application opinions diverge though. Apparently, the practical application mainly depends on the habit of the individual expert. We observed no consensus on the diagnostic criteria to be used. Given the potentially frequent use of the concept of the cardioinhibitory reflex in forensic practice and its judicial impact it would be important to reach a consensus.

Role of penicillin-binding proteins in Streptococcus gordonii

Résumé Streptococcus gordonii est une bactérie colonisatrice naturelle de la cavité buccale de l'homme. Bien que normalement commensale, elle peut causer des infections graves, telles que des bactériémies ou des endocardites infectieuses. La pénicilline étant un des traitements privilégiés dans de tels cas, l'augmentation rapide et globale des résistances à cet antibiotique devient inquiétante. L'étude de la physiologie et des bases génétiques de ces résistances chez S. gordonii s'avère donc importante. Les cibles moléculaires privilégiées de la pénicilline G et des β-lactames sont les penicilllin-binding proteins (PBPs). Ces enzymes associées à la membrane ont pour rôle de catalyser les réactions de transpeptidation et de transglycosylation, qui constituent les dernières étapes de la biosynthèse du peptidoglycan (PG). Elles sont définies comme classe A ou B selon leur capacité d'assurer soit les deux réactions, soit uniquement la transpeptidation. Les β-lactames inhibent le domaine transpeptidase de toutes les PBPs, entraînant l'inhibition de la synthèse du PG, l'inhibition de la croissance, et finalement la mort cellulaire. Chez les streptocoques, les PBPs sont aussi les premiers déterminants de la résistance à la pénicilline. De plus, elles sont impliquées dans la morphologie bactérienne, en raison de leur rôle crucial dans la formation du PG. Le but de ce travail était de caractériser les PBPs de S. gordonii et d'étudier leurs fonctions dans la vie végétative de la bactérie ainsi que durant le développement de la résistance à la pénicilline. Premièrement, des mutants auxquels il manque une ou deux PBP(s) ont été construits. Leur étude - au niveau physiologique, biochimique et morphologique - a montré le caractère essentiel ou dispensable de chaque protéine, ainsi que certaines de leurs fonctions potentielles. Deuxièmement, des mutants résistants à la pénicilline ont été générés. Leur caractérisation a montré l'importance des mutations dans les PBPs ainsi que dans d'autres gènes encore inconnus, de même que le rôle crucial des PBPs de classe A dans le développement de la résistance à la pénicilline. Des expériences supplémentaires sur des isolats résistants ont aussi prouvé que la résistance a un coût en terme de fitness, coût que S. gordonii parvient à compenser par des mécanismes d'adaptation. Finalement, les promoteurs des gènes des PBPs ont été déterminés et leur expression a été étudiée grâce au gène de luciférase. Il a ainsi été montré que la résistance à la pénicilline entraîne non seulement des altérations au niveau des protéines, mais aussi au niveau de la régulation des gènes. De plus, la pénicilline génère directement des modifications dans l'expression de PBPs spécifiques. Summary Streptococcus gordonii is a normal inhabitant of the human oral cavity and a pioneer colonizer of teeth. Although usually considered as a commensal, this organism can cause life-threatening infections such as bacteraemia or endocarditis. Since penicillin is one of the preferential treatments for such pathologies, the rapid and general increase of antibiotic resistance in the overall population becomes an issue. Thus, studying the physiologic and genetic bases of such a resistance in S. gordonii is of interest. The primary molecular targets of penicillin G and other β-lactams are the so called penicillin-binding proteins (PBPs). These are membrane-associated proteins that catalyze the last steps in peptidoglycan (PG) biosynthesis, namely transpeptidation and transglycosylation. Depending on their capacity to catalyze either reactions or only transpeptidation, they are considered as class A or class B PBPs, respectively. β-lactam antibiotics inhibit the transpeptidase domain of both of these classes of enzymes, resulting in inhibition of PG assembly, inhibition of bacterial growth, and ultimately leading to cell death. In streptococci, PBPs are also the primary determinants of penicillin-resistance. Moreover, because of their crucial role in PG formation, they are implicated in fundamental aspects of cell morphology. The goal of this work was thus to characterize S. gordonii PBPs and to explore their functions in terms of vegetative life and penicillin-resistance development. First, single and double PBP-inactivated mutants were generated and their effect on the bacterial physiology, cell wall biochemistry and ultrastructural morphology was assessed. This demonstrated the essentiality or dispensability of each protein for bacterial life. Second, penicillin-resistant mutants were generated by cyclic exposure to increasing concentrations of the drug. Characterization of these mutants pointed out the importance of both PBP and non-PBP mutations, as well as the crucial role of the class A PBPs in the development of penicillin-resistance. Further experiments on resistant isolates demonstrated the fitness cost of this resistance, but also the capacity of S. gordonii to adapt and regain the fitness of the wild-type. Finally, the promoters of PBP genes were determined and their expression was monitored using luciferase fusions. This showed that penicillin-resistance, in addition to modifications at the level of the protein, also triggered genetic alterations. Moreover, penicillin itself generated modifications in the expression of specific PBPs.

Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo.

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

Sleep disorders in children with cerebral palsy.

To determine the frequency and predictors of sleep disorders in children with cerebral palsy (CP) we analyzed the responses of 173 parents who had completed the Sleep Disturbance Scale for Children. The study population included 100 males (57.8%) and 73 females (42.2%; mean age 8y 10mo [SD 1y 11mo]; range 6y-11y 11mo). Eighty-three children (48.0%) had spastic diplegia, 59 (34.1%) congenital hemiplegia, 18 (10.4%) spastic quadriplegia, and 13 (7.5%) dystonic/dyskinetic CP. Seventy-three children (42.2%) were in Gross Motor Function Classification System Level I, 33 (19.1%) in Level II, 30 (17.3%) in Level III, 23 (13.3%) in Level IV, and 14 (8.1%) in Level V. Thirty children (17.3%) had epilepsy. A total sleep problem score and six factors indicative of the most common areas of sleep disorder in childhood were obtained. Of the children in our study, 23% had a pathological total sleep score, in comparison with 5% of children in the general population. Difficulty in initiating and maintaining sleep, sleep-wake transition, and sleep breathing disorders were the most frequently identified problems. Active epilepsy was associated with the presence of a sleep disorder (odds ratio [OR]=17.1, 95% confidence interval [CI] 2.5-115.3), as was being the child of a single-parent family (OR=3.9, 95% CI 1.3-11.6). Disorders of initiation and maintenance of sleep were more frequent in children with spastic quadriplegia (OR=12.9, 95% CI 1.9-88.0), those with dyskinetic CP (OR=20.6, 95% CI 3.1-135.0), and those with severe visual impairment (OR=12.5, 95% CI 2.5-63.1). Both medical and environmental factors seem to contribute to the increased frequency of chronic sleep disorders in children with CP.

Rates and determinants of virologic and immunological response to HAART resumption after treatment interruption in HIV-1 clinical practice.

OBJECTIVE: To describe CD4 and HIV RNA changes during treatment resumption (TR) after treatment interruption (TI) compared with response to first highly active antiretroviral therapy (HAART) and to investigate predictors. METHODS: Using Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) data, we identified subjects who interrupted first HAART, not initiated during primary infection. We estimated rate of CD4 change during TR and time from TR to HIV RNA<500 copies per milliliter and subsequent rebound and factors associated with these outcomes. RESULTS: Of 281 persons treated for median 18.4 months before interrupting, 259 resumed HAART. CD4 increases in the first 3 months on HAART were similar pre-TI and post-TI but after 3 months were significantly higher during pre-TI HAART, with median +106 and +172 cells per microliter at 3 and 18 months, respectively, during initial HAART compared with +99 and +142 cells per microliter during post-TI HAART, respectively. Subjects with lower CD4 counts at TI, aged older than 40 years, and those resuming the same HAART as their pre-TI regimen had lower CD4 increases during the first 3 months of TR. The majority (86%) of individuals reinitiating therapy achieved HIV RNA<500 copies per milliliter. CONCLUSIONS: Immune reconstitution after TI is generally poorer than after first HAART, particularly for patients aged older than 40 years at TI and those with poorer immunological responses to pre-TI HAART. Reinitiation of the same HAART regimen as pre-TI also seems to have unfavorable outcomes.

MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells.

The retinal pigment epithelium (RPE) is constantly exposed to external injuries which lead to degeneration, dysfunction or loss of RPE cells. The balance between RPE cells death and proliferation may be responsible for several diseases of the underlying retina, including age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Signaling pathways able to control cells proliferation or death usually involve the MAPK (mitogen-activated protein kinases) pathways, which modulate the activity of transcription factors by phosphorylation. UV exposure induces DNA breakdown and causes cellular damage through the production of reactive oxygen species (ROS) leading to programmed cell death. In this study, human retinal pigment epithelial cells ARPE19 were exposed to 100 J/m(2) of UV-C and MAPK pathways were studied. We first showed the expression of the three major MAPK pathways. Then we showed that activator protein-1 (AP-1) was activated through phosphorylation of cJun and cFos, induced by JNK and p38, respectively. Specific inhibitors of both kinases decreased their respective activities and phosphorylation of their nuclear targets (cJun and cFos) and reduced UV-induced cell death. The use of specific kinases inhibitors may provide excellent tools to prevent RPE apoptosis specifically in RPE diseases involving ROS and other stress-related compounds such as in AMD.

Peripheral T cells undergoing superantigen-induced apoptosis in vivo express B220 and upregulate Fas and Fas ligand.

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen (SAg) that predominantly interacts with V(beta)8+ T cells. In vivo treatment of mice with SEB leads to an initial increase in the percentage of V(beta)8+ T cells, followed by a decrease in the numbers of these cells, eventually reaching lower levels than those found before treatment with the SAg. This decrease is due to apoptosis of the SEB-responding cells. In the present study, we use the distinct light scattering characteristics of apoptotic cells to characterize T cells that are being deleted in response to SEB in vivo. We show that dying, SEB-reactive T cells express high levels of Fas and Fas ligand (Fas-L), which are implicated in apoptotic cell death. In addition, the B cell marker B220 is upregulated on apoptotic cells. Moreover, we show that the generation of cells with an apoptotic phenotype is severely impaired in response to SEB in functional Fas-L-deficient mutant gld mice, confirming the role of the Fas pathway in SAg mediated peripheral deletion in vivo.

Risk of death due to chronic chagasic cardiopathy

In this longitudinal study 5,710 people were included. The inclusion criteria were two positive serological results for Trypanosoma cruzi infection, 15 and 50 years old and no other demostrable diesease at the time of study. In the five year follow up 1,117 patients were lost. The follow up involved yearly evaluation of serology, clinical examination, X-ray of torax, and ECG, for 4,593 patients and 263 were contacted at home because they did not assist for their clinical consultant. Time average of follow up was 5.3 years. Eighty nine (1.5%) of the 4,593 patients died during the follow-up period, 63 (71%) by cardiac insufiency (CI) and 26 (29%) by severe ventricular arrithmias. Diagnosis of cardiomegaly was present in all the patients with diagnosis of CI and in 15 (5%) of the patients with diagnosis of arrithmias.The ECG alterations of these pacients show 61 right bundle brunch block (RBBB), associated or not with left anterior hemiblock (LAHB), 47 pathological Q wave and 70 primary repolarization alterations; 61 had polyfocal ventricular arrithmia. The death rate was similar in the sexes and was more frequent between 40 and 50 years of age. Information on 1,380 recuperated patients shows that 15 died with no previous symptoms and without medical assistance and were interpretate as sudden death. The latest ECG in three follow-up of these pacients indicates (before death) that only one had normal study and 14 presented 12 RBBB; 9 LAHB; 7 isolated ventricular arrithmia; 10 repolariz alterations; 2 patological Q wave, 10 patients of them with RBBB and repolariz alterations. In all the cases we had people between 35 and 43 years old, 9 men and 6 women. This study shows that in Chagas disease is possible to differenciate two risk groups. A low risk death group that have normal ECG and clinical evaluation during the follow up, and a high risk group associate ECG with RBBB and primary alterations of repolarization and/or inactivation zones with not anual clinical evaluation.

Nineteenth century research on cell death.

This paper reviews research on cell death in the 19th C. The first report of cell death was by Vogt in 1842, which was remarkably soon after the establishment of the cell theory by Schleiden and Schwann between 1838 and 1842. Initial studies on cell death, including that of Vogt, focused on its occurrence in metamorphosis (Vogt, 1842; Prévost and Lebert, 1844; Weismann, 1863-1866) or in blatant pathology (Virchow, 1858), but as histological techniques improved it was found to be involved in more subtle roles in numerous situations including endochondral ossification (Stieda, 1872), ovarian follicle atresia (Flemming, 1885), cell turnover (Nissen, 1886), the wholesale loss of a population of sensory neurons in fish (Beard, 1889), and the naturally occurring histogenetic death of myocytes (Felix, 1889) and neurons (Collin, 1906). The current categorization of cell death into about three main morphological types has 19th century roots in that apoptosis was well described by Flemming (1885), who called it chromatolysis, and various authors including Noetzel (1895) proposed a threefold classification. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".