Perirenal fat is related to carotid intima-media thickness in children.

BACKGROUND/OBJECTIVES: It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking. We investigated the relationship of perirenal fat and other abdominal fat depots (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal children, so as to identify novel markers that can be easily assessed and used in the early prevention of cardiovascular disease. SUBJECTS/METHODS: Subjects were 702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142 obese) who were recruited in a primary care setting. Ultrasound measurements (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT), clinical (body mass index (BMI) and systolic blood pressure) and metabolic parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin and serum lipids) were assessed. RESULTS: Perirenal fat was associated with diverse metabolic and CV risk factors in all the studied subjects. However, in overweight and obese children, perirenal fat was mostly associated with cIMT (P<0.001) and was the only fat depot that showed independent associations with cIMT in multivariate analyses (overweight chidren: ß=0.250, P=0.003, r2=12.8%; obese children: ß=0.254, P=0.002, r2=15.5%) after adjusting for BMI, gender, age and metabolic parameters. Perirenal fat was also the only fat depot that showed independent associations with HMW-adiponectin in obese children (ß=-0.263, P=0.006, r2=22.8%). CONCLUSIONS: Perirenal fat is the main abdominal fat depot associated with cIMT, especially in overweight and obese children, and may thus represent a helpful parameter for assessing CV risk in the pediatric population.

Glucagon-like peptide-1 improves beta-cell antioxidant capacity via extracellular regulated kinases pathway and Nrf2 translocation.

Oxidative stress plays an important role in the development of beta-cell dysfunction and insulin resistance, two major pathophysiological abnormalities of type 2 diabetes. Expression levels of antioxidant enzymes in beta cells are very low, rendering them more susceptible to damage caused by reactive oxygen species (ROS). Although the antioxidant effects of glucagon-like peptide-1 (GLP-1) and its analogs have been previously reported, the exact mechanisms involved are still unclear. In this study, we demonstrated that GLP-1 was able to effectively inhibit oxidative stress and cell death of INS-1E beta cells induced by the pro-oxidant tert-butyl hydroperoxide (tert-BOOH). Incubation with GLP-1 enhanced cellular levels of glutathione and the activity of its related enzymes, glutathione-peroxidase (GPx) and -reductase (GR) in beta cells. However, inhibition of ERK, but not of the PI3K/AKT pathway abolished, at least in part, the antioxidant effect of GLP-1. Moreover, ERK activation seems to be protein kinase A (PKA)-dependent because inhibition of PKA with H-89 was sufficient to block the GLP-1-derived protective effect on beta cells. GLP-1 likewise increased the synthesis of GR and favored the translocation of the nuclear transcription factor erythroid 2p45-related factor (Nrf2), a transcription factor implicated in the expression of several antioxidant/detoxificant enzymes. Glucose-stimulated insulin secretion was also preserved in beta-cells challenged with tert-BOOH but pre-treated with GLP-1, probably through the down-regulation of the mitochondrial uncoupling-protein2 (UCP2). Thus, our results provide additional mechanisms of action of GLP-1 to prevent oxidative damage in beta cells through the modulation of signaling pathways involved in antioxidant enzyme regulation.

Predominant role of GIP in the development of a metabolic syndrome-like phenotype in female Wistar rats submitted to forced catch-up growth.

Catch-up growth has been associated with the appearance of metabolic dysfunctions such as obesity and type 2 diabetes in adulthood. Because the entero-insular axis is critical to glucose homeostasis control, we explored the relevance of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the development of these pathologies. Offspring of rat dams fed ad libitum (control [C]) or 65% food-restricted during pregnancy and suckling time (undernourished [U]) were weaned onto a high-fat (HF) diet (CHF and UHF, respectively) to drive catch-up growth. Both male and female UHF rats showed an obese phenotype characterized by hyperphagy, visceral fat accumulation, and adipocyte hypertrophy. High-fat diet induced deterioration of glucose tolerance in a sex-dependent manner. Female UHF rats experienced much more severe glucose intolerance than males, which was not compensated by insulin hypersecretion, suggesting insulin resistance, as shown by homeostatic model assessment of insulin resistance values. Moreover, female, but not male, UHF rats displayed enhanced GIP but not GLP-1 secretion during oral glucose tolerance test. Administration of the GIP receptor antagonist (Pro3)GIP to UHF female rats over 21 days markedly reduced visceral fat mass and adipocyte hypertrophy without variations in food intake or body weight. These changes were accompanied by improvement of glucose tolerance and insulin sensitivity. In conclusion, the exacerbated production and secretion of GIP after the catch-up growth seems to represent the stimulus for insulin hypersecretion and insulin resistance, ultimately resulting in derangement of glucose homeostasis. Overall, these data evidence the role of GIP as a critical link between catch-up growth and the development of metabolic disturbances.

Role of endogenous IL-6 in the neonatal expansion and functionality of Wistar rat pancreatic alpha cells.

AIMS/HYPOTHESIS: Plasma glucagon concentrations rise sharply during the early postnatal period. This condition is associated with increased alpha cell mass. However, the trophic factors that regulate alpha cell turnover during the perinatal period have not been studied. Macrophage infiltrations are present in the neonatal pancreas, and this cell type releases cytokines such as IL-6. Alpha cells have been identified as a primary target of IL-6 actions. We therefore investigated the physiological relevance of IL-6 to neonatal pancreatic alpha cell maturation. METHODS: Histochemical analyses were performed to quantify alpha cell mass, replication and apoptosis. Pancreatic Il6 expression was determined by quantitative RT-PCR. The biological effect of IL-6 was tested in two in vivo rat models of IL-6 blockade and chronic undernutrition. RESULTS: Alpha cell mass increased sharply shortly after birth but decreased significantly after weaning. Pancreatic alpha cell proliferation was as high as 2.5% at the beginning of suckling but diminished with time to 1.2% in adulthood. Similarly, alpha cell neoformation was remarkably high on postnatal day (PN) 4, whereas alpha cell apoptosis was low throughout the neonatal period. Moreover, Il6 mRNA exhibited developmental upregulation in the pancreas of suckling rats, with the highest expression on PN2. Neutralisation of IL-6 reduced alpha cell mass expansion and glucagon production. IL-6 staining was detected within the islets, mainly in the alpha cells. Finally, undernourished neonates showed altered alpha cell number and function and delayed appearance of IL-6 in the pancreas. CONCLUSIONS/INTERPRETATION: These data point to a potential role for local IL-6 in the regulation of alpha cell growth and function during suckling.

Undernutrition upregulates fumarate hydratase in the rat nucleus accumbens.

Previous comparative studies of fumarate hydratase (FH) protein density revealed that the enzyme was overexpressed in the striatum of rodents that are less influenced by rewarding stimuli, from cocaine to food. Therefore, we recently proposed FH as a potential striatal biomarker of brain reward deficiency and addiction vulnerability. This work has been focused to investigate FH activity in the Nucleus Accumbens (NAc) of undernourished rats, taking into account that malnutrition has been related to increased responsiveness to food and drug reward. To this end, we have studied adult female Wistar rats severely food restricted from the 16th day of intrauterine life until adulthood. Animals were sacrificed to dissect the NAc and obtain mitochondrial and cytosolic fractions after homogenisation and centrifugation. FH activity was measured by conversion of malate to fumarate, and protein levels were compared by Western blot analysis when fractions showed differences in activity. Undernutrition did not change cytosolic FH activity but led to a marked increase of mitochondrial FH activity (72 %) and protein content (50 %) in the NAc. This change was in the opposite direction that one would predict if it was related to addiction vulnerability of some kind, but strongly suggests that mitochondrial FH needs to be at some optimal level for normal reward responsiveness.

Efecto inmunomodulardor de ampicilina, cefazolina y ciprofloxacina en pacientes con infeccion bacteriana internados en el hospital de clínicas de La Paz / Inmodulator effect of ampicilin, cefazoline and ciprofloxacine in patients whit bacterial infection at the hospital de clinicas of La Paz

Pregunta de investigación.-¿La ampicilina, cefazolina y ciprofloxacina tiene afecto inmunomodulador sobre la fagocitosis en pacientes con infección bacteriana? Diseño.- Estudio prospectivo, de tipo ensayo clínico con autocontrol. Lugar.- Laboratorio de Inmunologia dependiente del Instituto de Genética- Facultad de Medicina, UMSA y hospital de Clínicas, La Paz-Bolivia. Obejtivos.- Determinar si la ampicilina, cefazolina y ciprofloxacina tienen efecto inmunomodulador sobre la fagocitosis de PMSs (porcentaje, indice y actividad del radical subperóxido) en pacientes con infección bacteriana. Población de estudio.- 90 pacientes con infección bacteriana, internados en el Hospital General de la ciudad de La Paz, tanto en la Unidad de Cirugía varones- mujeres, como en el Instituto de Cirugia Plástica y quemados. Tamaño de muestra.- La determinación del número de muestra se la estableció sobre la base del grado de confianza y presición del experimento, donde el número adecuado fue de 30 repeticiones para cada antibiótico.Procedieminto.- Los pacientes recibieron esquema de tratameinto antibiótico correspondiente (ampicilina o ciproxacina) a dosis y tiempos terapéuticos. En todas las muestras obtenidas se determinó el porcentaje e indice de fagocitosis mediante la preuba de capacidad de fagocitosis y el orcentaje actividad del radical subperóxido mediante la prueba de Nitroazul de Tetrazolium. Resultados.- La ampicilina mostró efecto estimlador sobre le porcentaje de fagocitosis al terminar el tratameinto (p

Efecto inmunomodulador de la Ciprofloxacina sobre la función Fagocítica de Polimorfonucleares Neutrófilos / Effect immune modulaator of the citofloxacina upon the functions phagocytic of polymorphous nuclearis nuetrofilos

Las fagocitosis se determinó utilizando S. aureus (porcentaje e índice de fagocitosis). La reducción del NBT se evaluó con sangre sin anticoagulante en placa. Para el análisis estadístico se utilizó la técnica de Student para medias emparejadas. El porcentaje de fagocitosis disminuyó significativamente con el estímulo de la amplicilina tanto a los 30 como a los 60 minutos, mientras que la ciprofloxacina no mostró ningún efecto sobre esta función. El índice fagocítico también disminuyó significativamente a los 60 minutos tanto con estímulo de ampicilina como de ciprofloxacina, mientras que a los 30 minutos no se observaron cambios con ninguno de los antibióticos. La reducción del NBT no se vio afectada por el estímulo de ampicilina ni ciprofloxacina en ninguno de los tiempos de estímulo

Estudio del perfil inmunologico en la mujer gestante a termino y en el recien nacido / Study of the inmunologic profile in the pregnant women and the new-born

Con el objeto de determinar las modificaciones del sistema inmunologico en la mujer gestante y en el recien nacido, por efecto del parto se analizaron los valores de globulos blancos, inmunoglobinas y complemento en ambas, se estudiaron 52 mujeres gestantes con embarazo de 36 a 41 semanas sin enfermedad antes ni durante el embarazo en trabajo de parto, que consultan al Instituto "Natalio Aramayo" asi como tambien a los recien nacidos de parto eutosico y distosico. Se tomaron muestras sanguineas de sangre periferica (madre) y de cordon umbilicar (recien nacido) con y sin anticoagulante para dosificacion de inmunoglobulinas y recuento de leucocitos. El recuento de leucocitos en la gestante fue de 11.369 /uL mm3 con un minimo de 5.500 y un maximo de 24.600 (SD 6300/uL) mientras que en el recien nacido fue de 11.030 mm3 (SD 3600/mm3). El recuento diferencial fue: polimorfonucleares en un 86.46 por ciento y linfocitos en un 13.53 por ciento. En el recien nacido: PMN en un 76,61 por ciento y linfocitos en un 23.07 por ciento. Los valores obtenidos para las inmunoglobulinas fueron: en la madre IgG 1.434 mg/dL; IgM 215.38 mg/dL; IgA 244,46 mg/dL; C3 154 mg/dL y C4 30.7 mg/dl. En el recien nacido IgG 1514 mg/dL; IgA 2,46 mg/dL; IgM 11.46 mg/dL; C3 92.3 mg/dL y C4 21.1 mg/dL. Se pudo constatar la leucocitosis de la gestante a predominio de PMN. Por los valores obtenidos se concluye que el parto distosico condiciona el aumento de IgG, tanto en niños como en la madre (P<0.05), esta relacion se invierte en la madre (p<0.05). Se debera realizar un nuevo estudio valorando el sistema inmune en la etapa de post parto mediato y tardio.

[Acute retroviral syndrome]. / Síndrome retroviral agudo.

A 37 year old male developed fever for 20 days, along with headache, anorexia, malaise, sweating, pharyngitis, lymphadenopathy and splenomegaly. At this stage, Ag p24 was positive and anti HIV was negative. The patient recovered fully but 6 months later positive HIV titers were demonstrated by immunofluorescence and Western-blot. A retrospective diagnosis of acute retroviral syndrome was made. The difficult differential diagnosis with infectious mononucleosis, cytomegalovirus, measles, rubella, toxoplasmosis and influenza is discussed. Thus, anti HIV antigenemia should be investigated in any patient with a mononucleosis like syndrome belonging in a high risk group for AIDS, even if Paul-Bunnell-Davidson or IgG anti VCA-EB reactions are positive.

[In vitro activity of ampicillin and ampicillin-sulbactam on diverse bacteria]. / Actividad in vitro de ampicilina y ampicilina-sulbactam sobre diversas bacterias.

A foremost mechanism of bacterial resistance to penicillin and its derivatives is the chromosomal or plasmid mediated production of B-lactamase. Inhibitors of these enzymes like sulbactam may help overcome this problem. We tested the in vitro activity of ampicillin alone or in association with sulbactam (1:1 ratio) against enterobacteriaceae, aeromonae, Hemophilus influenzae, staphylococci and Streptococcus fecalis, isolated from patients suffering different infectious diseases. The Kirby-Bauer method was used to evaluate susceptibility and MIC was determined by agar dilution techniques. Most enterobacteriaceae and aeromonae were resistant to ampicillin. The association was effective against shigellae and Yersinia enterocolitica. 28% of H. influenzae strains were resistant to ampicillin alone but were susceptible to the association. 30% of resistant staphylococci became sensitive to the association.