Caloric restriction attenuates aging-induced cardiac insulin resistance in male Wistar rats through activation of PI3K/Akt pathway.

BACKGROUND AND AIM: Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging-induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of caloric restriction (CR) preventing the aging-induced insulin resistance in the heart of male Wistar rats. METHODS AND RESULTS: Three experimental groups were used: 3 months old rats (3m), 24 months old rats (24m) and 24 months old rats subjected to 20% CR during their three last months of life (24m-CR). After sacrifice hearts were mounted in a perfusion system (Langendorff) and heart function in basal conditions and in response to accumulative doses of insulin (10-9-10-7 M), in the presence or absence of Wortmannin (10-6 M), was recorded. CR did not attenuate the aging-induced decrease in coronary artery vasodilation in response to insulin administration, but it prevented the aging-induced downregulation of cardiac contractility (dp/dt) through activation of the PI3K/Akt intracellular pathway. Insulin stimulated in a greater extent the PI3K/Akt pathway vs the activation of the MAPK pathway and increased the protein expression of IR, GLUT-4 and eNOS in the hearts of 3m and 24m-CR rats, but not in the hearts of 24m rats. Furthermore, CR prevented the aging induced increase in endothelin-1 protein expression in myocardial tissue. CONCLUSION: In conclusion CR partially improves cardiac insulin sensitivity and prevents the aging induced decrease in myocardial contractility in response to insulin administration through activation of PI3K/Akt pathway.

Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue.

BACKGROUND AND AIMS: The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II). METHODS AND RESULTS: On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats. CONCLUSION: EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue.

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

PURPOSE: Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. MATERIAL AND METHODS: Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). RESULTS: Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. CONCLUSIONS: In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

The metabolic response to postnatal leptin in rats varies with age and may be litter dependent.

Hyperleptinemia during postnatal life induces long-term effects on metabolism. However, these effects are controversial as both increased and decreased propensity towards obesity has been reported. To further analyze the effects of chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar rats proceeding from 18 different litters (8 pups/litter) received a daily subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 µg/g, n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150 days of age. At 10 days of age, leptin treated rats had decreased body weight (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At PND150 neonatal leptin treatment induced different effects in rats raised in different litters. Rats from litter 1 had increased body weight (p<0.05), body fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In rats from litter 2 these parameters did not differ from controls. Rats from litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to postnatal leptin varies with age, with the response in adulthood being variable and most likely influenced by other factors, including the genetic make-up.

Marjoram extract prevents ischemia reperfusion-induced myocardial damage and exerts anti-contractile effects in aorta segments of male wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marjoram (Origanum majorana L.) is an herb traditionally used as a medicine in different countries, as Morocco and Iran, because of its beneficial cardiovascular effects. Some studies suggest that these effects are due, at least in part, to the presence of phenolic compounds such as rosmarinic acid (RA) and luteolin. AIM OF THE STUDY: To analyze the possible cardiprotective effects of a marjoram extract (ME) reducing myocardial damage after coronary ischemia-reperfusion (IR) and its possible antihypertensive effects reducing the response of aorta segments to the vasoconstrictors noradrenaline (NA) and endothelin-1 (ET-1). MATERIALS AND METHODS: Male Wistar rats (300g) were used. After sacrifice, the heart was immediately removed and mounted in a perfusion system (Langendorff). The aorta was carefully dissected and cut in 2 mm segments to perform vascular reactivity experiments. RESULTS: In the heart, ME perfusion after IR reduced heart rate and prevented IR-induced decrease of cardiac contractility, possibly through vasodilation of coronary arteries and through the upregulation of antioxidant markers in the myocardium that led to reduced apoptosis of cardiomyocytes. In the aorta, ME decreased the vasoconstrictor response to NA and ET-1 and exerted a potent anti-inflammatory and antioxidant effect. Neither RA nor 6-hydroxi-luteolin-O-glucoside, major compounds of this ME, were effective in improving cardiac contractility after IR or attenuating vasoconstriction to NA and ET-1 in aorta segments. CONCLUSION: In conclusion, ME reduces the myocardial damage induced by IR and the contractile response to vasoconstrictors in the aorta. Thus, it may be useful for the treatment of cardiovascular diseases such as myocardial infarction and hypertension.

Role of hormones in sarcopenia.

Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.

Epidemiology of tuberculosis in the Americas: the Stop TB strategy and the millennium development goals.

BACKGROUND: Tuberculosis (TB), a preventable and curable disease, remains a major public health threat in the poorest regions of the Americas. The DOTS strategy was implemented to control TB in the region in 1993, and the new Stop TB strategy, emphasizing high-quality DOTS expansion, in 2006. OBJECTIVES: To describe TB epidemiology in the region of the Americas from 1994 to 2005 and to analyze the progress made towards and prospects for achieving Goal 6 of the Millennium Development Goals (MDGs) by 2015. METHODS: TB incidence, mortality and prevalence rates as well as DOTS coverage and DOTS treatment success rates were collated from the World Health Organization (WHO) databases from 1994 to 2005. RESULTS: DOTS coverage and DOTS treatment success rates rose steadily from 1994 to 2005, with 88% of the population covered under DOTS by 2005, and an 80% success rate by the end of 2004. The TB incidence, prevalence and mortality rates have also decreased steadily from 1994 to date, but differ with respect to the various scenarios. CONCLUSIONS: With the exception of some countries, further reduction in TB incidence, prevalence and deaths by 2015 is possible. Widespread implementation of DOTS should continue in order to meet WHO targets and attain the MDGs.

[Post viral onychomadesis outbreak in Valladolid]. / Brote de onicomadesis posvírica en Valladolid.

INTRODUCTION: An onychomadesis outbreak associated with hand-foot-mouth disease (HFMD) was notified in winter 2008 in Valencia, Spain, with more than 200 people affected, the majority children. Even though this association has already described, this was the first outbreak known in the world. Sixteen cases of post-viral onychomadesis post viral in Valladolid are presented MATERIAL AND METHODS: Between November 2008 and February 2009, 15 children aged between 18 months and 3 years, and one mother, presented with onychomadesis in Primary Care Centres in Valladolid. RESULTS: HFMD was diagnosed in a single month in 11 patients who attended two nurseries. The others attended others nurseries of Valladolid area. Nine children (60%) had the clinical diagnosis of HFMD 3 to 12 weeks before (mean: 6 weeks), six with fever. The nail changes were usually temporary with spontaneous normal re-growth in 1 to 4 months. CONCLUSIONS: The clinical and epidemiological characteristics of this report were similar to the Valencia outbreak: age, geographic clustering, acral eruption prior, etc. Perhaps the diagnosis is underestimated due to ignorance of the disease and the long interval between the acute viral process and nail shedding.

Scaling up collaborative TB-HIV activities in Latin America.

TB-HIV collaborative activities are one of the cornerstones of TB control in the Stop TB strategy. Since 2003, most countries in Latin America and the Caribbean have been gradually implementing TB-HIV collaborative activities; however, limited information is currently available on the degree of implementation. This study is therefore aimed at describing to what degree TB-HIV collaborative activities are being implemented in 17 countries selected for the study. These countries were asked to complete a semi-structured questionnaire. An analysis of this questionnaire revealed that the challenges for TB-HIV collaboration lie in the fields of human resources, surveillance and HIV testing of TB patients.

Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue.

The prevalence of metabolic syndrome is dramatically increasing among elderly population. Metabolic syndrome in aged individuals is associated with hyperinsulinemia and insulin resistance both in metabolic tissues and in the cardiovascular system, with this fact being associated with the cardiometabolic alterations associated to this condition. Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of CR in aging-induced vascular insulin resistance both in aortic rings and in primary culture of endothelial cells. In addition, the inflammatory profile of perivascular adipose tissue (PVAT) and its possible role in the impairment of vascular insulin sensitivity associated with aging was also assessed. Three experimental groups of male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats subjected to 20% CR during their three last months of life (24m-CR). Aorta rings surrounded or not by PVAT were mounted in an organ bath and precontracted with phenylephrine (10-7.5M). Changes in isometric tension were recorded in response to cumulative insulin concentrations (10-8-10-5.5M) in the presence or absence of L-NAME (10-4M). Aortic rings and primary aortic endothelial cells were incubated in presence/absence of insulin (10-7M) and the activation of the PI3K/Akt and MAPK pathways as well as nitrite and nitrates concentrations and the mRNA levels of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the aging-induced decrease in the vasodilator response to insulin and the aging-induced increase in the vasoconstrictor response to high insulin concentrations. Changes between 24m and 24m-CR aorta rings were abolished in the presence of L-NAME. CR induced-improvement in insulin vascular sensitivity was related with activation of the PI3K/Akt both in aortic rings and in aortic endothelial cells in response to insulin. CR attenuated the overexpression of iNOS, TNF-α and IL-1ß in the PVAT of aged rats although aortic rings surrounded by PVAT from 24m rats showed and increased vasorelaxation in response to insulin compared to aortic rings from 3m and 24m-CR rats. In conclusion, a moderate protocol of CR improves insulin vascular sensitivity and prevents the aging induced overexpression of pro-inflammatory cytokines in PVAT.

Population and methodology of the SIMETAP study: Prevalence of cardiovascular risk factors, cardiovascular diseases, and related metabolic diseases. / Población y metodología del estudio SIMETAP: Prevalencia de factores de riesgo cardiovascular, enfermedades cardiovasculares y enfermedades metabólicas relacionadas.

The prevention of cardiovascular disease is based on the detection and control of cardiovascular risk factors (CVRF). In Spain there are important geographical differences both in the prevalence and in the level of control of the CVRF. In the last decade there has been an improvement in the control of hypertension and dyslipidaemia, but a worsening of cardio-metabolic risk factors related to obesity and diabetes. The SIMETAP study is a cross-sectional descriptive, observational study being conducted in 64 Primary Care Centres located at the Community of Madrid. The main objective is to determine the prevalence rates of CVRF, cardiovascular diseases, and metabolic diseases related to cardiovascular risk. A report is presented on the baseline characteristics of the population, the study methodology, and the definitions of the parameters and diseases under study. A total of 6,631 study subjects were selected using a population-based random sample. The anthropometric variables, lifestyles, blood pressure, biochemical parameters, and pharmacological treatments were determined. The highest crude prevalences were detected in smoking, physical inactivity, obesity, prediabetes, diabetes, hypertension, dyslipidaemias, and metabolic syndrome. A detailed analysis needs to be performed on the prevalence rates, stratified by age groups, and prevalence rates adjusted for age and sex to assess the true epidemiological dimension of these CVRF and diseases.

Results of PAL feasibility test in primary health care facilities in four regions of Bolivia.

SETTING: Primary health care (PHC) centres in four Bolivian regions. OBJECTIVES: To test the feasibility and impact of training general practitioners (GPs) in standard case management of respiratory conditions in patients aged > or =5 years. DESIGN: Comparison of the results of two surveys: the baseline survey before training and the impact survey after training on standard guidelines on case management of respiratory conditions. RESULTS: A total of 78 GPs working in 65 health centres participated in both surveys. The baseline survey registered 1033 respiratory patients and the impact survey 1154. The patients were comparable in sex distribution, previous visits, duration of symptoms and clinical diagnoses. The differences were significant in age distribution, concomitant diseases and risk factors. As a result of training, referrals to a higher level decreased by 34.6% and the proportion of tuberculosis (TB) suspects identified increased by 30%. The number of drugs prescribed per patient decreased by 16.2%. The average cost of prescription of any drug per patient dropped by 32.3%. CONCLUSION: Training in the standard practical approach to lung health guidelines improved the quality and reduced the cost of treatment of respiratory diseases at PHC units. Training should be an integral part of a comprehensive managerial approach for the implementation of case management guidelines.

HR007: a family of biomaterials based on glycosaminoglycans for tissue repair.

Most new advances in tissue engineering (TE) focus on the creation of adequate microenvironments that may accelerate the repair processes of damaged tissues. Extracellular matrix (ECM) of Wharton's jelly (WJ) from umbilical cords is very rich in sulphated GAGs (sGAGs) and hyaluronic acid (HA), components which have special properties that could positively influence the regeneration of several types of tissue. Previously, we described the methodology for the extraction and purification of GAGs from WJ and, importantly, the separation of sGAGs and HA to develop various scaffolds for regenerative medicine. In this new study we hypothesized that the biomaterials obtained, called HR007s, would be excellent candidates for two different applications, chondral and dermal repair. First, we have confirmed that the GAGs obtained are biocompatible, as they do not cause cytotoxicity, haemolysis or an inflammatory response. Second, we have developed three-dimensional (3D) structures through the combination of different ratios of GAGs and their subsequent stabilization, which can be properly adapted to target tissues, cartilage or skin. Finally, we have combined these scaffolds with adipose mesenchymal stem cells (ASCs) or fibroblasts for application to chondral or dermal defects, respectively, with the goal of promoting fast reparative processes. The results show that HR007 scaffolds induce cell proliferation, enhance the expression of specific gene markers, increase the production of tissue ECM proteins and have chemotactic effects over the studied cells. In summary, the bioactive properties of HR007 scaffolds make them promising candidates for use in regenerative medicine, at least for chondral and dermal repair. Copyright © 2015 John Wiley & Sons, Ltd.

Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression.

Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-alpha (TNF-alpha) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-alpha. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats.

Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund's adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-alpha, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitin-ligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.

Policies and practices on the programmatic management of latent tuberculous infection: global survey.

SETTING: Global survey among low tuberculosis (TB) burden countries, which are primary target countries for the World Health Organization (WHO) guidelines on the programmatic management of latent tuberculous infection (LTBI). OBJECTIVE: To perform a baseline assessment of policies and practices for the programmatic management of LTBI. DESIGN: Online and paper-based pre-tested questionnaire filled out by national TB programme managers or their equivalents from 108 countries. RESULTS: Of 74 respondent countries, 75.7% (56/74) had a national policy on LTBI. The majority of the countries (67/74, 90.5%) provided LTBI testing and treatment for child contacts of TB cases, while almost two thirds (49/74, 66%) reported provision of LTBI testing and treatment to people living with the human immunodeficiency virus (PLHIV). Six countries (8.1%) did not report providing LTBI management to child contacts and PLHIV. Among countries that reported both the availability of policy and practice of testing and treatment of LTBI for at-risk populations, a system for recording and reporting data was available in 62% (33/53) for child contacts and in 53% (21/40) for PLHIV. CONCLUSION: Countries need to ensure that national LTBI policies and a standardised monitoring and evaluation system are in place to promote the programmatic management of LTBI.

Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats.

While it is well known that sepsis inhibits serum IGF-I and its gene expression in the liver, the effect on pituitary GH and IGF-binding protein-3 (IGFBP-3) is poorly understood. The GH-IGF-I-IGFBP-3 response to different doses of lipopolysaccharide (LPS) administration has been investigated in adult male rats. Two experiments were performed, administration of low doses of LPS (5, 10, 50 and 100 microg/kg) and high doses of LPS (100, 250, 500 and 1000 microg/kg). Rats received two i.p. injections of LPS (at 1730 h and 0830 h the following day) and were killed 4 h after the second injection. LPS administration induced a biphasic response in serum concentrations of GH, with an increase at the 10 microg/kg dose, followed by a decrease at higher doses (100 microg/kg on up). Pituitary GH mRNA was also increased by the administration of 10 and 50 microg/kg LPS, whereas at higher doses LPS did not modify pituitary GH mRNA. We also analyzed the GH response to LPS in primary pituitary cell cultures. When exposed to LPS, in the culture medium, there was an increase in GH release at the concentration of 0.1 and 10 ng/ml, whereas more concentrated LPS did not modify GH release. Serum concentrations of IGF-I declined in a dose-dependent fashion after LPS administration in the rats injected with 10 microg/kg LPS on up. This decrease is secondary to modifications in its synthesis in the liver, since endotoxin injection decreased both IGF-I and its mRNA in the liver. The liver GH receptor mRNA was also decreased by LPS administration, but only in the animals injected with high LPS doses. There was a decrease in both the IGFBP-3 serum levels and its gene expression in the liver with all LPS doses studied. These data suggest a biphasic LPS effect on pituitary GH, a stimulatory effect at low doses and an inhibitory effect at higher doses, whereas it has a clear inhibitory effect on IGF-I and IGFBP-3 synthesis in the liver. The decrease in liver IGFBP-3 mRNA and in serum concentrations of IGFBP-3 in the rats injected with LPS may contribute to the decrease in serum concentrations of IGF-I.

[Blood lead in a population of children with iron deficiency]. / Estudio de la plumbemia en la población infantil con ferropenia.

BACKGROUND: Analysis of blood lead levels in relation to the state of iron metabolism was carried out in children. METHODS: A transversal study of blood lead levels was designed in 89 iron deficient children (serum ferritin < 15 micrograms/l) (group F). Fifty seven of the children did not have anemia (sub-group FS) and 32 had anemia (sub-group AF) with ages ranging between 6 months and 14 years, and 41 children of the same age with normal iron metabolism (group C). A longitudinal study was also carried out by the determination of blood lead levels prior and after iron therapy in 18 of the iron deficient children. RESULTS: A significant difference was seen between the mean of blood lead levels in iron deficient children (group F), 9.41 micrograms/dl and normal children (group C), 6.88 micrograms/dl (p < 0.01). The mean of blood lead levels of the sub-group FS was 7.79 micrograms/dl and the sub-group AF, 12.30 micrograms/dl (p < 0.01). The prevalence of lead poisoning (blood lead levels > 20 micrograms/dl) was 8% in group F (2% in sub-group FS, 19% in sub-group AF) and 0 in group C (p < 0.01). A significant decrease was found in the longitudinal study in the mean of blood lead levels following iron therapy from 14.12 micrograms/dl to 7.51 micrograms/dl (p < 0.05). CONCLUSIONS: The iron deficient state may constitute a predisposing factor of lead poisoning in childhood.

[Early presentation of breakthrough varicella in vaccinated children]. / Aparición temprana de varicela modificada en niños vacunados con una dosis.

INTRODUCTION: The introduction of a routine varicella vaccination program for children has achieved a significant reduction in morbidity and mortality due to varicella. However, there is still an incidence of chickenpox in those vaccinated, called "varicella breakthrough" (VB). This has led to the inclusion of a 2nd dose vaccination schedule, at an age which could be too late. PATIENTS AND METHODS: This study presents 23 cases of children diagnosed with VB (mean age at diagnosis 4.85 years) who had been vaccinated with one dose of varicella vaccine (mean age of vaccination 2.37 years). RESULTS: The mean time between the vaccine and the disease was 2.48 years, with a median of 2.0 years. VB was diagnosed in 13% of children who had been vaccinated the previous year, and 52% diagnosed in the previous two. Therefore many of these patients had suffered the disease before the recommended time of administration of the second dose of vaccine according to the current vaccine schedules. CONCLUSIONS: To avoid these vaccine failures, it would be appropriate to bring the two doses of varicella vaccine closer, or even assess the pattern of two consecutive doses.

Successful management of multidrug-resistant tuberculosis under programme conditions in the Dominican Republic.

SETTING: The Dominican Republic is a high-incidence area for multidrug-resistant tuberculosis (MDR-TB; 6.6% of initial cases). Standardised treatment regimens for MDR-TB may be a potential solution. OBJECTIVE: To present the effectiveness of standard regimens under routine national conditions. DESIGN: We reviewed all MDR-TB patients treated under routine conditions from 29 August 2006 to 30 June 2010, showing interim and final outcomes. Patients were treated with regimens that were standardised or individualised based on previously received second-line anti-tuberculosis drugs. RESULTS: Population description and culture conversion data are reported for the 289 MDR-TB patients. The median patient age was 31 years. Most had failed first-line treatment (72.6%). Culture negativity was obtained within 4 months (median 2 months) in 78.6%. Among the 150 patients treated between 2006 and 2008, 74% had favourable results on standardised and 66% on individualised regimens (P = 0.211). The efficacy of the standardised and individualised regimens was respectively 92.8% and 81% (P = 0.056). The relapse rate was approximately 1%. A median of five drug side effects occurred per patient. More than 2 months to culture conversion and bilateral cavitation on chest X-ray were found to be unfavourable outcome risk factors. CONCLUSIONS: Standardised MDR-TB regimens may be effective at the national level, even in resource-poor settings.