Oligodeoxynucleotide IMT504: Effects on Central Nervous System Repair Following Demyelination.

Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) disease characterized by demyelination resulting from oligodendrocyte loss and inflammation. Cuprizone (CPZ) administration experimentally replicates MS pattern-III lesions, generating an inflammatory response through microgliosis and astrogliosis. Potentially remyelinating agents include oligodeoxynucleotides (ODN) with a specific immunomodulatory sequence consisting of the active motif PyNTTTTGT. In this work, the remyelinating effects of ODN IMT504 were evaluated through immunohistochemistry and qPCR analyses in a rat CPZ-induced demyelination model. Subcutaneous IMT504 administration exacerbated the pro-inflammatory response to demyelination and accelerated the transition to an anti-inflammatory state. IMT504 reduced microgliosis in general and the number of phagocytic microglia in particular and expanded the population of oligodendroglial progenitor cells (OPCs), later reflected in an increase in mature oligodendrocytes. The intracranial injection of IMT504 and intravenous inoculation of IMT504-treated B lymphocytes rendered comparable results. Altogether, these findings unveil potentially beneficial properties of IMT504 in the regulation of neuroinflammation and oligodendrogenesis, which may aid the development of therapies for demyelinating diseases such as MS.

Path Loss Characterization in an Outdoor Corridor Environment for IoT-5G in a Smart Campus University at 850 MHz and 3.5 GHz Frequency Bands.

The usage scenarios defined in the ITU-M2150-1 recommendation for IMT-2020 systems, including enhanced Mobile Broadband (eMBB), Ultra-reliable Low-latency Communication (URLLC), and massive Machine Type Communication (mMTC), allow the possibility of accessing different services through the set of Radio Interface Technologies (RITs), Long-term Evolution (LTE), and New Radio (NR), which are components of RIT. The potential of the low and medium frequency bands allocated by the Federal Communications Commission (FCC) for the fifth generation of mobile communications (5G) is described. In addition, in the Internet of Things (IoT) applications that will be covered by the case of use of the mMTC are framed. In this sense, a propagation channel measurement campaign was carried out at 850 MHz and 5.9 GHz in a covered corridor environment, located in an open space within the facilities of the Pedagogical and Technological University of Colombia campus. The measurements were carried out in the time domain using a channel sounder based on a Universal Software Radio Peripheral (USRP) to obtain the received signal power levels over a range of separation distances between the transmitter and receiver from 2.00 m to 67.5 m. Then, a link budget was proposed to describe the path loss behavior as a function of these distances to obtain the parameters for the close-in free space reference distance (CI) and the floating intercept (FI) path loss prediction models. These parameters were estimated from the measurements made using the Minimum Mean Square Error (MMSE) approach. The estimated path loss exponent (PLE) values for both the CI and FI path loss models at 850 MHz and 3.5 GHz are in the range of 2.21 to 2.41, respectively. This shows that the multipath effect causes a lack of constructive interference to the received power signal for this type of outdoor corridor scenario. These results can be used in simulation tools to evaluate the path loss behavior and optimize the deployment of device and sensor network infrastructure to enable 5G-IoT connectivity in smart university campus scenarios.

Long-term exposure to ambient fine particulate matter and carotid intima media thickness at bilateral, left and right in adults from Mexico City: Results from GEA study.

BACKGROUND: PM2.5 exposure has been associated with intima-media thickness (cIMT) increase. However, very few studies distinguished between left and right cIMT in relation to PM2.5 exposure. AIM: To evaluate associations between chronic exposure to PM2.5 and cIMT at bilateral, left, and right in adults from Mexico City. METHODS: This study comprised 913 participants from the control group, participants without personal or family history of cardiovascular disease, of the Genetics of Atherosclerosis Disease Mexican study (GEA acronym in Spanish), recruited at the Instituto Nacional de Cardiología Ignacio Chávez from June 2008 to January 2013. To assess the associations between chronic exposure to PM2.5 (per 5 µg/m3 increase) at different lag years (1-4 years) and cIMT (bilateral, left, and right) we applied distributed lag non-linear models (DLNMs). RESULTS: The median and interquartile range for cIMT at bilateral, left, and right, were 630 (555, 735), 640 (550, 750), and 620 (530, 720) µm, respectively. Annual average PM2.5 exposure was 26.64 µg/m3, with median and IQR, of 24.46 (23.5-25.46) µg/m3. Results from DLNMs adjusted for age, sex, body mass index, low-density lipoproteins, and glucose, showed that PM2.5 exposure for year 1 and 2, were positively and significantly associated with right-cIMT [6.99% (95% CI: 3.67; 10.42) and 2.98% (0.03; 6.01), respectively]. Negative associations were observed for PM2.5 at year 3 and 4 and right-cIMT; however only year 3 was statistically significant [-2.83% (95% CI: 5.12; -0.50)]. Left-cIMT was not associated with PM2.5 exposure at any lag year. The increase in bilateral cIMT followed a similar pattern as that observed for right-cIMT, but with lower estimates. CONCLUSIONS: Our results suggest different susceptibility between left and right cIMT associated with PM2.5 exposure highlighting the need of measuring both, left and right cIMT, regarding ambient air pollution in epidemiological studies.

Intrathecal Administration of an Anti-nociceptive Non-CpG Oligodeoxynucleotide Reduces Glial Activation and Central Sensitization.

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.

Oligonucleotide IMT504 Improves Glucose Metabolism and Controls Immune Cell Mediators in Female Diabetic NOD Mice.

Type 1 diabetes occurs as a consequence of progressive autoimmune destruction of beta cells. A potential treatment for this disease should address the immune attack on beta cells and their preservation/regeneration. The objective of this study was to elucidate whether the immunomodulatory synthetic oligonucleotide IMT504 was able to ameliorate diabetes in NOD mice and to provide further understanding of its mechanism of action. We found that IMT504 restores glucose homeostasis in a diabetes mouse model similar to human type 1 diabetes, by regulating expression of immune modulatory factors and improving beta cell function. IMT504 treatment markedly improved fasting glycemia, insulinemia, and homeostatic model assessment of beta cell function (HOMA-Beta cell) index. Moreover, this treatment increased islet number and decreased apoptosis, insulitis, and CD45+ pancreas-infiltrating leukocytes. In a long-term treatment, we observed improvement of glucose metabolism up to 9 days after IMT504 cessation and increased survival after 15 days of the last IMT504 injection. We postulate that interleukin (IL)-12B (p40), possibly acting as a homodimer, and Galectin-3 (Gal-3) may function as mediators of this immunomodulatory action. Overall, these results validate the therapeutic activity of IMT504 as a promising drug for type 1 diabetes and suggest possible downstream mediators of its immunomodulatory effect.

IMT504 Provides Analgesia by Modulating Cell Infiltrate and Inflammatory Milieu in a Chronic Pain Model.

IMT504 is a non-CPG, non-coding synthetic oligodeoxinucleotide (ODN) with immunomodulatory properties and a novel inhibitory role in pain transmission, exerting long-lasting analgesic effects upon multiple systemic administrations. However, its mechanisms of anti-nociceptive action are still poorly understood. In the present study in male adult rats undergoing complete Freund's adjuvant-induced hindpaw inflammation, we focused in the analysis of the immunomodulatory role of IMT504 over the cellular infiltrate, the impact on the inflammatory milieu, and the correlation with its anti-allodynic role. By means of behavioral analysis, we determined that a single subcutaneous administration of 6 mg/kg of IMT504 is sufficient to exert a 6-week-long full reversal of mechanical and cold allodynia, compromising neither acute pain perception nor locomotor activity. Importantly, we found that the anti-nociceptive effects of systemic IMT504, plus quick reductions in hindpaw edema, were associated with a modulatory action upon cellular infiltrate of B-cells, macrophages and CD8+ T-cells populations. Accordingly, we observed a profound downregulation of several inflammatory leukocyte adhesion proteins, chemokines and cytokines, as well as of ß-endorphin and an increase in the anti-inflammatory cytokine, interleukin-10. Altogether, we demonstrate that at least part of the anti-nociceptive actions of IMT504 relate to the modulation of the peripheral immune system at the site of injury, favoring a switch from pro- to anti-inflammatory conditions, and provide further support to its use against chronic inflammatory pain. Graphical abstract GA short description - IMT504 systemic Administration. Systemic administration of the non-CpG ODN IMT504 results in a 6-week long blockade of pain-like behavior in association with anti-inflammatory responses at the site of injury. These include modulation of lymphoid and myeloid populations plus downregulated expression levels of multiple pro-inflammatory cytokines and ß-endorphin. Nocifensive responses and locomotion remain unaltered.

Single-stranded oligodeoxynucleotides induce plant defence in Arabidopsis thaliana.

BACKGROUND AND AIMS: Single-stranded DNA oligodeoxynucleotides (ssODNs) have been shown to elicit immune responses in mammals. In plants, RNA and genomic DNA can activate immunity, although the exact mechanism through which they are sensed is not clear. The aim of this work was to study the possible effect of ssODNs on plant immunity. KEY RESULTS: The ssODNs IMT504 and 2006 increased protection against the pathogens Pseudomonas syringae pv. tomato DC3000 and Botrytis cinerea but not against tobacco mosaic virus-Cg when infiltrated in Arabidopsis thaliana. In addition, ssODNs inhibited root growth and promoted stomatal closure in a concentration-dependent manner, with half-maximal effective concentrations between 0.79 and 2.06 µm. Promotion of stomatal closure by ssODNs was reduced by DNase I treatment. It was also diminished by the NADPH oxidase inhibitor diphenyleneiodonium and by coronatine, a bacterial toxin that inhibits NADPH oxidase-dependent reactive oxygen species (ROS) synthesis in guard cells. In addition it was found that ssODN-mediated stomatal closure was impaired in bak1-5, bak1-5/bkk1, mpk3 and npr1-3 mutants. ssODNs also induced early expression of MPK3, WRKY33, PROPEP1 and FRK1 genes involved in plant defence, an effect that was reduced in bak1-5 and bak1-5/bkk1 mutants. CONCLUSIONS: ssODNs are capable of inducing protection against pathogens through the activation of defence genes and promotion of stomatal closure through a mechanism similar to that of other elicitors of plant immunity, which involves the BAK1 co-receptor, and ROS synthesis.

Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women.

BACKGROUND: Atherosclerosis is a primary risk factor for cardiovascular disease (CVD). Proinflammatory biochemical factors can influence vascular health; monocyte chemoattractant protein-1 (MCP-1) is elevated in patients with CVD while fibroblast growth factor-21 (FGF-21) acts directly on cardiac tissue to reduce infarction damage. However, the relationship between plasma concentrations of MCP-1, FGF-21 and subclinical CVD indices remains equivocal. AIM: To determine the association between MCP-1, FGF-21 and subclinical atherosclerosis [i.e., carotid intima-media thickness (cIMT)] in women without clinical evidence of CVD. METHODS: A cross-sectional analysis of 140 women without history of CVD was performed. Anthropometrics were collected, serum concentrations of MCP-1 and FGF-21 were determined by enzyme-linked immunosorbent assay, and cIMT was quantified (B-mode ultrasonography). The correlations between MCP-1, FGF-21 and the presence of clinical and laboratory of subclinical atherosclerosis (i.e., cIMT ≥0.70 mm), comparison intergroup and odd ratio with multiple logistic regression were analyzed. RESULTS: MCP-1, but not FGF-21 correlated with some obesity indicators. In median comparison among groups, subclinical atherosclerosis showed higher serum concentrations of MCP-1and lower serum concentrations of FGF-21. In postmenopausal women, there were significant differences MCP-1 (p = 0.001), and FGF-21 (p = 0.010). Multiple logistic regression analysis in postmenopausal women with subclinical atherosclerosis, between MCP-1 (p = 0.001) and FGF-21 (p = 0.037) showed association with cIMT, along with age. CONCLUSIONS: MCP-1 and FGF-21 levels are associated with subclinical atherosclerosis disease severity (i.e., cIMT) in postmenopausal women without CVD. Further efforts focused on characterizing the relationship between novel blood-borne markers of early CVD pathology are warranted and should be pursued.

Correlation between serum 25-hydroxyvitamin D levels and carotid intima-media thickness in a Brazilian population descended from African slaves

Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (β=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy.

The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

Association between carotid intima-media thickness and adiponectin in participants without diabetes or cardiovascular disease of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective The study assessed the association of adiponectin concentration with carotid intima-media thickness (CIMT) in middle-aged participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease. Design Cross-sectional analyses. Methods A sample of 687 individuals (35-54 years old) without diabetes or cardiovascular disease was stratified into two categories according to CIMT (< or ≥ 75th percentile). Traditional risk factors, C-reactive protein and adiponectin values were compared between categories by Student's t-test and frequencies by chi-square test. In linear regression models, associations of CIMT with adiponectin, adjusted for adiposity, blood pressure, C-reactive protein and homeostasis model assessment-insulin resistance were tested. Mean CIMT values were compared across quartiles of adiponectin concentrations using analysis of variance. Results Three hundred and forty-one individuals (49.6%) were women and 130 (19.0%) had three traditional cardiovascular risk factors. Those with elevated CIMT (21.8%) had greater mean values of body mass index (26.2(3.8) vs. 27.7(4.0)kg/m2, p < 0.001), waist circumference (86.9(10.1) vs. 90.1(10.8) cm, p = 0.001), systolic blood pressure (116.2(13.6) vs.121.2(16.1) mmHg, p < 0.001), homeostasis model assessment index (1.4(0.9-2.4) vs. 1.8(1.1-2.9), p = 0.011), C-reactive protein (1.2 (0.6-2.6) vs. 1.4(0.8-3.2) mg/l, p = 0.054) and adiponectin (9.9 (6.0-14.7) vs. 8.9 (5.3-13.8) µg/ml, p = 0.002) levels than the counterpart, while plasma glucose and lipids were not different between groups. In the adjusted model, blood pressure (directly) and adiponectin (inversely) persisted associated with high CIMT. Mean CIMT was greater in the first quartile of adiponectin when compared with the other three quartiles ( p = 0.019). Conclusions Lower adiponectin levels together with higher blood pressure were independently associated with elevated CIMT. Adiponectin concentration may be an independent marker of early structural damage in individuals at low-to-moderate cardiovascular risk.

Evaluación de la adiponectina y su correlación con la íntima media carotidea en mujeres peri y post menopáusicas hospital de engativá, bogotá

El riesgo cardiovascular (RCV), se incrementa en las mujeres después de la menopausia. La adiponectina, se postula como un biomarcador de riesgo cardiovascular. La presente investigación buscó conocer si los niveles de adiponectina y la evaluación de a Intima Media Carotidea (IMT) se modifican durante el climaterio. Se evaluó el riesgo cardiovascular a diez años, en la escala de Framingham (FRS). Se tomaron 80 pacientes, entre 45 y 65 años, de la consulta de Climaterio en el Hospital de Engativá, Bogotá, entre el 15 de enero y 15 de diciembre de 2015. Las pacientes, se dividieron en dos grupos: 46 perimenopáusicas y 34 posmenopáusicas, todas las participantes firmaron el consentimiento informado. En formulario precodificado, se consignaron las variables sociodemográficas, examen físico, valores química sanguínea y resultados de ecografía doppler de carótida. La edad media entre los dos grupos fue: 50,95 años y 60,59 años. Se evidenció diferencia significativa en la presión arterial media. No hubo diferencia estadística en el perímetro abdominal ni en el Índice de Masa Corporal (IMC). La adiponectina presentó diferencia significativa intra grupos. No hubo diferencia en el perfil lipídico, el riesgo cardiovascular aumentó significativamente entre las mujeres pre y postmenopáusicas. La evaluación de la Íntima Media Carotidea (IMT) evidenció diferencias significativas en la placa anterior y posterior, tanto de carótida derecha como de carótida izquierda. El índice de pulsatilidad (IP) fue significativo en la carótida derecha y no en la izquierda. Se postula que la adiponectina es un marcador de riesgo cardiovascular y la IMT útil en la evaluación de arterioesclerosis.

The cardiovascular risk (CVR) increases in women after menopause. Adiponectin is postulated as a biomarker of cardiovascular risk. This study sought to determine whether adiponectin levels and assessment of Carotid Intima Media (IMT) are modified during the climacteric. cardiovascular risk ten years in the Framingham (FRS) was evaluated. 80 patients between 45 and 65 years of consulting Climaterio at the Hospital of Engativá, Bogota, between January 15 and December 15, 2015. The patients were divided into two groups, 46 perimenopausal and 34 postmenopausal, all participants signed informed consent. In pre-encoded form sociodemographic variables, physical examination, blood chemistry values and results of carotid doppler ultrasound were recorded. The average age between the two groups was: 50.95 years and 60.59 years. Significant difference was evidenced in mean arterial pressure. There was no statistical difference in waist circumference or the Body Mass Index (BMI). Adiponectin showed a significant difference intra groups. There was no difference in lipid profile, cardiovascular risk increased significantly between preand postmenopausal women. Evaluation of Carotid Intima Media showed significant differences in the anterior and posterior plates both right and left carotid carotid. The pulsatility index (PI) was significant in the right carotid artery and not in the left. We hypothesize that adiponectin is a marker of cardiovascular risk and IMT useful in assessing atherosclerosis.

Insulin resistance and carotid intima-media thickness mediate the association between resting-state heart rate variability and executive function: A path modelling study.

BACKGROUND: Research has linked high-frequency heart rate variability (HF-HRV) to cognitive function. The present study adopts a modern path modelling approach to understand potential causal pathways that may underpin this relationship. METHODS: Here we examine the association between resting-state HF-HRV and executive function in a large sample of civil servants from Brazil (N=8114) recruited for the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). HF-HRV was calculated from 10-min resting-state electrocardiograms. Executive function was assessed using the trail-making test (version B). RESULTS AND CONCLUSIONS: Insulin resistance (a marker of type 2 diabetes mellitus) and carotid intima-media thickness (subclinical atherosclerosis) mediated the relationship between HRV and executive function in seriatim. A limitation of the present study is its cross-sectional design; therefore, conclusions must be confirmed in longitudinal study. Nevertheless, findings support that possibility that HRV provides a 'spark' that initiates a cascade of adverse downstream effects that subsequently leads to cognitive impairment.

Associations of life course socioeconomic position and job stress with carotid intima-media thickness. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

RATIONALE: The association between life course socioeconomic position (SEP) and subclinical atherosclerosis is not consistent across studies. Socioeconomic adversities early in life are related to an increased probability of a low occupational grade and more stressful jobs in adulthood. However, the role of job stress in explaining the life course social gradient in subclinical atherosclerosis is unknown. OBJECTIVES: To examine whether life course SEP is associated with carotid intima-media thickness (IMT) and to investigate whether this association is partially mediated by job stress. METHODS: This study used baseline data (2008-2010) for 8806 current workers from ELSA-Brasil. Maternal education, social class of first occupation and social class of current occupation were used to evaluate childhood, youth and adulthood SEP, respectively. Accumulation of risk across the life course was also evaluated. Job stress was assessed by the Swedish Demand-Control-Support Questionnaire. Directed acyclic graph and linear regression models were used. RESULTS: Low childhood SEP was associated with increased IMT only in women, but low youth and adulthood SEP were associated with higher IMT in both genders. The simultaneous adjustment for all SEP indicators showed that only adulthood SEP continued to be associated with IMT. However, higher IMT values were observed among men and women sequentially exposed to low SEP in more than one period of life. High-strain jobs and low job control were not associated with IMT independent of SEP. CONCLUSION: Our results support a model of the cumulative effects of exposures to SEP across the life span because the highest IMT values were observed in individuals sequentially exposed to low SEP in more than one period of life. We did not find that job stress explained the association between life course SEP and IMT, suggesting that strategies to address socioeconomic inequalities in CVD should target additional steps beyond reducing job stress.

Enfermedad de Hansen asociado a Síndrome de Reconstitución Inmune en Pacientes con VIH/SIDA

Introducción: El Instituto de Medicina Tropical es un centro de referencia para enfermedades tropicales e infecciosas de Paraguay. Se expone la coincidencia entre la infección por el Virus de la Inmunodeficiencia Humana (VIH) y su estado terminal el Síndrome de Inmunodeficiencia Adquirida (SIDA) con la lepra, pues ambas tienen en común un deterioro del sistema inmunitario y una misma ubicación geográfica. Se analiza esta coinfección en diferentes países y su evolución, no siendo más frecuente esta asociación que el VIH en los grupos control. Objetivo: El objetivo de este trabajo es comunicar nuestra experiencia del tratamiento de la lepra en pacientes con VIH/SIDA. Materiales y métodos. Mediante el análisis de las historias clínicas de los pacientes con diagnóstico de Lepra y VIH/SIDA, se evaluó el tratamiento y el estado inmunológico. Resultados. A lo largo del periodo de estudio se trataron 6 pacientes con lepra y VIH. De ellos el 66.6% eran hombres, con el 33.3% (2 pacientes) menores de 30 años, 50% de ellos Lepra Bordeline Lepromatosa y 50% LB Tuberculoide. Al momento del estudio, 5 pacientes habían terminado el tratamiento, quedando uno con tratamiento hasta febrero del 2014 cumpliendo de manera regular. Conclusión. Se concluye que existe una asociación entre el estado inmunológico de los pacientes y la del diagnóstico de Lepra. Pretendemos proseguir la vigilancia de ambas endemias en los próximos años.

Abstract Background: The Institute of Tropical Medicine is a reference center for tropical and infectious diseases of Paraguay. The coincidence between infection HIV (HIV) and terminally Acquired Immune Deficiency Syndrome (AIDS) is exposed to leprosy, as both have in common a deterioration of the immune system and a geographic location. We analyzed this coinfection in different countries and their evolution, being this association not more frequent than HIV association in the control groups. Objective: The objective of this study was to report our experience in treating leprosy patients with HIV / AIDS. Materials and methods. Through the analysis of medical records of patients diagnosed with leprosy and HIV / AIDS, treatment and immune status was assessed. Results. Throughout the study period, 6 patients with leprosy and HIV were discussed. Of these, 66.6% were men, 33.3% (2 patients) under 30, 50% of them Borderline lepromatous leprosy and 50% LB Tuberculoid. At the time of the study, 5 patients had completed the treatment, leaving one treatment until February 2014 meeting regularly. Conclution. We conclude that there is an association between the immune status of patients and the diagnosis of leprosy. We intend to continue monitoring both endemic in the coming years

[Carotid and brachial intima-media thickness of the allelic variants G894T and T-789C of eNOS in systemic sclerosis patients]. / Grosor íntima-media de las variantes alélicas G894T y T-789C de eNOS en pacientes con esclerosis sistémica.

OBJECTIVE: To evaluate comparatively the carotid intima media thickness index (IMT) and brachial index with Doppler ultrasound, and pulmonary artery pressure with echocardiography in allelic variation of G894T and T-789C eNOS (endothelial nitric oxide synthase) in patients with systemic sclerosis. METHODS: This is a cross-sectional study in patients with scleroderma. The inclusion criteria were: age 18-70 years, scleroderma diagnosed patients with a prior informed consent. Polymorphism G894T and T-789C of eNOS was measured in blood, and IMT by carotid and brachial Doppler. We analyzed with descriptive statistics, Student's t test or chi square for association of variables and Spearman to correlate Doppler parameters. RESULTS: We found abnormally high IMT in carotid and brachial arteries. We also observed low correlation between both brachial arteries, good correlation between carotids and no correlation between carotid and brachial arteries. The left IMT>0.65 mm in brachial artery corresponds to pulmonary pressure>30 mmHg by echocardiography. G894T gene polymorphism was associated with increased IMT in right carotid. CONCLUSION: The G894T eNOS polymorphism was associated with increased IMT in right carotid. The one side carotid IMT is consistent with its contralateral. The left brachial IMT above to 0.65 mm, suggests the possibility of pulmonary arterial hypertension.

Introducción: el objetivo de este estudio es evaluar comparativamente el grosor íntima-media (IMT) carotídeo y braquial con ultrasonido Doppler, la presión arterial pulmonar ecocardiográfica y la variación alélica de los genes G894T y T-789C de la eNOS en pacientes con esclerodermia. Métodos: estudio transversal en pacientes con esclerodermia. Criterios de inclusión: edad 18-70 años, diagnosticado con esclerodermia, previo consentimiento informado. Se evaluó IMT, índice de resistencia (IR) e índice de pulsatilidad (IP) mediante Doppler carotídeo y braquial, perfil de lípidos, proteína C reactiva, polimorfismo G894T y T-789C de óxido nítrico sin tasa endotelial (eNOS). Analizamos con estadística descriptiva, prueba t de Student o chi cuadrada para asociación de variables y Spearman para correlacionar las variables cuantitativas. Resultados: encontramos IMT anormalmente alto en arterias carotídeas y braquiales. Observamos baja correlación entre ambas braquiales, buena correlación entre carótidas y ninguna correlación entre carótidas y braquiales. El IMT braquial izquierdo > 0.65 corresponde con presión arteria pulmonar > 30 mmHg ecocardiográfica. El polimorfismo del gen G894T se asoció con mayor IMT en carótida derecha.Conclusión: El polimorfismo G894T de eNOS se asocia a mayor IMT en carótida derecha. El IMT carotídeo concuerda con su IMT contralateral. El IMT braquial izquierdo mayor a 0.65 sugiere la posibilidad de hipertensión arterial pulmonar.

Endothelial dysfunction in children within 5 years after onset of Kawasaki disease.

OBJECTIVE: To evaluate endothelial function in children within 5 years after the onset of Kawasaki disease (KD). STUDY DESIGN: A total of 46 children were enrolled prospectively as follows: 9 patients with KD and coronary artery lesions composed group 1, 15 patients with KD but without coronary artery lesions composed group 2, and 22 healthy age- and sex-matched children composed group 3. Flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness of the common carotid artery, and biologic characteristics were compared among the 3 groups. Differences in the factors associated with endothelial function after KD were examined as well. RESULTS: The mean age of the study group was 6.5 ± 1.7 years. The patients with KD were studied at a median interval of 3.3 years (IQR, 2.0-4.4 years) from the onset of disease. The percent FMD (%FMD) was significantly lower in group 1 patients (median, 4.4%; IQR, 2.6%-5.7%) compared with both group 2 (median, 9.1%; IQR 6.6%-10.7%; P < .01) and group 3 (median, 11.1%; IQR, 10.1%-13.9%, P < .01). The %FMD was statistically significantly lower in group 2 compared with group 3 (P < .05). There were no significant differences in the intima-media thickness among the 3 groups. There was a significant negative correlation between %FMD and the total duration of fever (r = -0.50; P = .013). CONCLUSION: The children with KD already had arterial endothelial dysfunction within 5 years after the onset of illness. The longer the duration of fever, the greater the risk of inflammation-induced endothelial dysfunction.

Relationship between carotid intima-media thickness and metabolic syndrome in adolescents.

OBJECTIVE: To test the hypothesis that metabolic syndrome (MetS) is more predictive of carotid intima-media thickness (IMT) than the sum of the individual components of MetS. STUDY DESIGN: We analyzed the relationships between 2 definitions of the MetS and IMT in 461 overweight adolescents aged 10-18 years (median body mass index, 28.6 kg/m(2)). We used regression models and receiver operating characteristics (ROCs) for increased IMT (defined as ≥0.7 mm). RESULTS: The prevalence of MetS was 15.0% and 26.9% according to the 2 definitions applied. At the group level, quantitative IMT was associated with body mass index, blood pressure, glucose levels at 2 hours in an oral glucose tolerance test, and with each of the MetS components (all P < .05). At an individual level, using the MetS definitions alone as a diagnostic test for the presence of increased IMT (area under the ROC curve, 0.60-0.66) was inferior when compared with the sum of all individual components (area under the ROC curve, 0.65-0.85). Adding the presence or absence of MetS to the components did not improve the accuracy. CONCLUSION: Overweight adolescents with MetS demonstrated increased IMT values compared with overweight adolescents without MetS. The best model for diagnosing increased IMT was the sum of the quantitative components of MetS. The use of dichotomized variables reduced the diagnostic accuracy. Thus, in clinical practice, treatment of overweight adolescents should be based on weighing cardiovascular risk factors themselves, rather than on the dichotomous variable MetS.

Vascular effects of bisphosphonates-a systematic review.

BACKGROUND: Osteoporosis and cardiovascular disease are interconnected entities with pathophysiological similarities. Bisphosphonates are therapeutic options available for resorptive bone diseases; however, experimental evidence has demonstrated a role for bisphosphonates in the inhibition of atherogenesis. METHODS: A systematic review of the vascular effects of bisphosphonates on atherosclerosis was performed. Vascular effects were evaluated by the thickening of the intima-media of carotid arteries and calcification of the coronary and aorta arteries. Electronic databases PubMed, The Cochrane Library, and Embase from January 1980 to May 2011 were searched. RESULTS: Of 169 potentially relevant articles, 9 clinical trials were selected. Two articles showed the benefit of the use of etidronate (-0.038 mm, P < 0.005) and alendronate (-0.025 mm, P < 0.05) on carotid artery intima-media thickening (CIMT) after one year. One article found no changes associated with the use of alendronate. The use of risedronate was associated with a reduction of plaque score on the carotid arteries (decrease of 1% at 1 year, P = 0.015). Of those studies that evaluated the effect on coronary artery calcification (CAC), the results are conflicting: one study showed no changes with use of etidronate and in another, etidronate resulted in inhibition of the process of CAC after 1 year of follow-up (-372 mm(3) in CAC score, P < 0.01). Three studies showed positive effects of etidronate on the aortic calcificaton (AC) score, showing no effect with use of ibandronate, and another showed a inhibition in the progression of the abdominal AC score with use of risendronate (P = 0.043). CONCLUSION: Bisphosphonates seem to have an inhibitory effect on the atherosclerotic process; however, larger placebo-controlled studies are needed to better clarify this issue.