Development of Anxiolytic and Depression-like Behavior in Mice Infected with Mycobacterium lepraemurium.

Murine leprosy is a systemic infectious disease of mice caused by Mycobacterium lepraemurium (MLM) in which the central nervous system (CNS) is not infected; nevertheless, diseased animals show measurable cognitive alterations. For this reason, in this study, we explored the neurobehavioral changes in mice chronically infected with MLM. BALB/c mice were infected with MLM, and 120 days later, the alterations in mice were evaluated based on immunologic, histologic, endocrine, neurochemical, and behavioral traits. We found increases in the levels of IL-4 and IL-10 associated with high bacillary loads. We also found increase in the serum levels of corticosterone, epinephrine, and norepinephrine in the adrenal gland, suggesting neuroendocrine deregulation. Mice exhibited depression-like behavior in the tail suspension and forced swimming tests and anxiolytic behavior in the open field and elevated plus maze tests. The neurobehavioral alterations of mice were correlated with the histologic damage in the prefrontal cortex, ventral hippocampus, and amygdala, as well as with a blood-brain barrier disruption in the hippocampus. These results reveal an interrelated response of the neuroimmune--endocrinological axis in unresolved chronic infections that result in neurocognitive deterioration.

Reliability of a computer-aided system in the evaluation of indeterminate ultrasound images of thyroid nodules.

Introduction: Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images. Methods: US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images. Results: In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02). Conclusions: Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

Naegleria fowleri immunization modifies lymphocytes and APC of nasal mucosa.

We investigated whether intranasal immunization with amoebic lysates plus cholera toxin modified the populations of T and B lymphocytes, macrophages and dendritic cells by flow cytometry from nose-associated lymphoid tissue (NALT), cervical lymph nodes (CN), nasal passages (NP) and spleen (SP). In all immunized groups, the percentage of CD4 was higher than CD8 cells. CD45 was increased in B cells from mice immunized. We observed IgA antibody-forming cell (IgA-AFC) response, mainly in NALT and NP. Macrophages from NP and CN expressed the highest levels of CD80 and CD86 in N. fowleri lysates with either CT or CT alone immunized mice, whereas dendritic cells expressed high levels of CD80 and CD86 in all compartment from immunized mice. These were lower than those expressed by macrophages. Only in SP from CT-immunized mice, these costimulatory molecules were increased. These results suggest that N. fowleri and CT antigens are taking by APCs, and therefore, protective immunity depends on interactions between APCs and T cells from NP and CN. Consequently, CD4 cells stimulate the differentiation from B lymphocytes to AFC IgA-positive; antibody that we previously found interacting with trophozoites in the nasal lumen avoiding the N. fowleri attachment to nasal epithelium.

The yin/yang of inflammatory status: Blood-brain barrier regulation during sleep.

Sleep loss induces a low-grade inflammatory status characterized by a subtle but sustained increase of pro-inflammatory mediators, which are key regulators of blood-brain barrier function. To investigate the influence of inflammatory status on blood-brain barrier dysfunction induced by sleep restriction we performed an experiment using two strains of mice with different immunological backgrounds, C57BL/6 mice that have a predominant pro-inflammatory response and BALB/c mice that have a predominant anti-inflammatory response. Mice were sleep-restricted during 10 days using the flowerpot technique during 20 h per day with 4 h of daily sleep opportunity. The systemic inflammatory status, blood-brain barrier permeability, and the hippocampal expression of neuroinflammatory markers were characterized at the 10th day. Serum levels of TNF and IFN-γ increased in sleep-restricted C57BL/6 but not in BALB/c mice; no changes in other cytokines were found. Sleep restriction increased blood-brain barrier permeability in C57BL/6 strain but not in BALB/c. The hippocampus of sleep-restricted C57BL/6 mice exhibited an increase in the expression of the neuroinflammatory markers Iba-1, A2A adenosine receptor, and MMP-9; meanwhile in sleep-restricted BALB/c mice the expression of this markers was lesser than the control group. These data suggest that cytokines may be playing a key role in modulating blood-brain barrier function during sleep restriction, and probably the effects are related to Iba-1, MMP-9 and A2A adenosine receptor overexpression.

Neutrophils extracellular traps damage Naegleria fowleri trophozoites opsonized with human IgG.

Naegleria fowleri infects humans through the nasal mucosa causing a disease in the central nervous system known as primary amoebic meningoencephalitis (PAM). Polymorphonuclear cells (PMNs) play a critical role in the early phase of N. fowleri infection. Recently, a new biological defence mechanism called neutrophil extracellular traps (NETs) has been attracting attention. NETs are composed of nuclear DNA combined with histones and antibacterial proteins, and these structures are released from the cell to direct its antimicrobial attack. In this work, we evaluate the capacity of N. fowleri to induce the liberation of NETs by human PMN cells. Neutrophils were cocultured with unopsonized or IgG-opsonized N. fowleri trophozoites. DNA, histone, myeloperoxidase (MPO) and neutrophil elastase (NE) were stained, and the formation of NETs was evaluated by confocal microscopy and by quantifying the levels of extracellular DNA. Our results showed N. fowleri induce the liberation of NETs including release of MPO and NE by human PMN cells as exposure interaction time is increased, but N. fowleri trophozoites evaded killing. However, when trophozoites were opsonized, they were susceptible to the neutrophils activity. Therefore, our study suggests that antibody-mediated PMNs activation through NET formation may be crucial for antimicrobial responses against N. fowleri.

Consecuencia del abuso de alcohol / A consequence of alcohol abuse

No disponible

Effects of two calculolytic diets on parameters of feline mineral metabolism.

OBJECTIVES: To evaluate the influence of two feline calculolytic diets on selected parameters of mineral metabolism. MATERIALS AND METHODS: Two dry commercial diets designed for struvite urolith dissolution were evaluated in 14 cats. The study was designed as a two-sequence, four-period crossover protocol with a baseline period, two 60-day "run-in" periods in which calculolytic diets (Diet 1 and Diet 2) were fed and one 30-day "wash-out" period. Data are expressed as median (range). RESULTS: Feeding the calculolytic diets for two months did not alter plasma concentrations of calcium, phosphorus, magnesium and parathyroid hormone. A significant (P < 0.05 in each case) decline in calcitriol was observed after administering both diets from 236.4 (122.4-429.6) to 170.4 (108.0-394.3) pmol/L (Diet 1) and from 278.4 (153.6-492.0) to 177.1 (87.6-392.4) pmol/L (Diet 2). Cats fed Diet 1 showed a significant increase in urine calcium concentration (from 0.3 (0.2-0.5) to 0.4 (0.3-0.7) mmol/L). Magnesium concentration in urine was significantly increased with both diets, from 1.4 (0.1-1.7) to 1.5 (1.3-2.4) mmol/L (Diet 1) and from 1.1 (0.4-1.9) to 2.0 (0.1-3.1) mmol/L (Diet 2). CLINICAL SIGNIFICANCE: Both diets resulted in an increased urinary concentration of magnesium, through different mechanisms: urine acidification (Diet 1) and increased sodium load (Diet 2).

Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention.

Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.

Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.

This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.

La comunicación social en la promoción de la salud / Mass communication in health promotion

Fundamentos: En la actualidad encontramos en Venezuela una creciente presencia de la información periodística en salud en medios impresos, aunque este crecimiento no necesariamente ha ido acompañado de mayor calidad en el manejo y formulación, tanto de los temas como de los productos periodísticos. El objetivo de este trabajo es analizar las características de las informaciones de salud publicadas en los dos periódicos más importantes de Venezuela a lo largo de una década.Métodos: Se investigaron las características del periodismo en salud que se ha desarrollado en Venezuela en las secciones especializadas de dos periódicos de gran circulación a lo largo de una década. Se analizaron 522 informaciones: 246 de El Universal y 276 de El Nacional durante los años 1996 a 2006.Resultados: Los resultados preliminares presentan tendencias que muestran trivialización de la información, así como superficialidad en el manejo de los temas. Se proponen desafíos frente a los vacíos informativos y opciones para convertir la comunicación para la salud en una oportunidad para el desarrollo y el cambio social.Conclusión: Los resultados de la investigación podrían explicar por qué muchos autores perciben que la información periodística en salud resulta trivial o sobresimplificada: el predominio de los géneros más efímeros o acotados, como la noticia o la nota informativa, así como la dependencia de las fuentes vivas, utilizadas generalmente en número escaso, parecen condenar a los lectores a la pobreza informativa, a la falta de pluralidad, de equilibrio y de profundidad(AU)

Background: Currently found in Venezuela a growing presence of journalism in print media, health information though this growth has not necessarily been accompanied by higher quality in management and development issues as newspaper products. This work aims to analyze the characteristics of the health information published in the two major newspapers in Venezuela for a decade.Methods: Investigated the characteristics of journalism in health that has developed in Venezuela in the sections of two newspapers of wide circulation along a decade. We analyzed 522 reports: 246 of El Universal and 276 of El Nacional during the years 1996 to 2006.Results: Preliminary results that show the trivialization of the information andsuperficiality in handling the issues. Proposed challenges facing the information gaps and options for converting communication for health in an opportunity for development and social change.Conclusion: The results of the investigation could explain why many authors perceive press information on health as trivial: more ephemeral or bounded information as the news or information notes, as well as the limited use of living sources, seem to condemn readers to poor information in the absence of plurality, balance and depth(AU)

Metabolic acidosis inhibits soft tissue calcification in uremic rats.

Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other soft-tissue calcifications in uremic rats treated with calcitriol. Extraskeletal calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without ammonium chloride-induced acidosis. Soft-tissue calcification was assessed histologically, by measurement of the expression of the sodium-dependent phosphate cotransporter Pit-1 and by quantification of tissue calcium and phosphorus. Calcitriol administration to uremic rats resulted in significant deposition of material positive for von Kossa stain in the aorta, stomach, and kidney, elevated aortic calcium and phosphorus, increased aortic Pit-1 expression, and high mortality. Calcitriol-treated uremic rats with acidosis did not develop aortic or soft-tissue calcification, did not increase aortic Pit-1 expression, and had significantly lower mortality. Additionally, an acidotic environment prevented calcification of vascular smooth muscle cells in vitro. Our study shows that metabolic acidosis inhibits extraskeletal calcification.

[Fulminant sepsis caused by Vibrio vulnificus. A case series]. / Sepsis fulminante por Vibrio vulnificus. Serie de casos.

BACKGROUND: Vibrio vulnificus is a marine bacteria associated with the ingestion of raw shellfish or contact with seawater. It can produce wound infection, diarrhea and sepsis. The main risk factor for infection is the presence of chronic liver disease. Prior studies have shown mortality from 40% to 63%. OBJECTIVE: Report of 8 cases of disseminated infection with V. vulnificus causing fulminant sepsis. DESIGN: Series of cases. METHODS: We reviewed the database of the laboratory of clinical microbiology from 1990 to 1999. A computer-based review of the worldwide medical literature was also accomplished. RESULTS: There were 8 cases of V. vulnificus infection. All patients had chronic liver disease, 3 also had diabetes mellitus and 1 received immunosuppressive agents. Five patients were known to have ingested raw shellfish. The mean duration of illness before death was 4 days. All patients presented with sepsis, seven had cutaneous lesions. Five patients received early antimicrobial treatment during the first 24 hours and all of them in the first 48 hours. Regardless of susceptibility to the antimicrobial agents used, the mortality was of 87.5%. Disk-diffusion test showed 100% susceptibility to imipenem, ceftazidime and tetracycline; 83% to cefepime, ticarcillin and cotrimoxazole and 50% to quinolones. CONCLUSION: The V. vulnificus infection appears in patients with chronic liver disease and it is associated with high mortality. This infection has to be suspected in high-risk patients who have eaten raw shellfish and therapy must be initiated as soon as possible.

Formulación, fabricación y evaluación de una fórmula láctea para el programa nacional de alimentación complementaria en Chile / Formulation, fabrication and evaluation of a cow's milk formula to Complementary Feeding National Program in Chile

El Programa Nacional de Alimentación Complementaria (PNAC) entrega 2 kg-mes de leche entera de vaca en polvo (LP) a niños de 0 a 1 año. El objetivo del trabajo fue diseñar, fabricar y evaluar la estabilidad de una fórmula láctea nutricionalmente más balanceada para este grupo etario y de costo similar al de LP para ser incorporada al PNAC. La fórmula, denominada LP Modificada (LPM), se caracteriza por: P%12,0 (LP 21,8%); relación caseína/lactosuero: 40-50/60-50 (LP 80/20); grasas de mayor digestibilidad; ácidos grasos esenciales: 4%de calorías totales; vitaminas y minerales cubren 100%de los requerimientos diarios para 0 a 6 meses de edad; que permite modular aporte proteico entre 1,5 y 2,25 g-100 ml y el aporte calórico entre 50 y 75 kcal-100 ml. Se fabricaron 40 ton de LPM para el estudio en terreno de acuerdo a especificaciones técnicas elaboradas por nosotros. El control de calidad del producto demostró la factibilidad tecnológica de producirlo a un costo inferior a LP. Para determinar la estabilidad se analizaron peróxidos, lisina disponible, ácido ascórbico y ácido linoleico en LPM almacenada a 20-C y 37-C por un año, encontrándose que LPM en el mismo envase que LP tiene una duración óptima de 7 meses. La incorporación de LPM al PNAC debería considerar la entrega mínima de 3 kg-mes al grupo de 0 a 1 año. Esto significa en relación a 2 kg-mes de LP un aporte adecuado de proteínas y un aumento del aporte calórico de 50%con un costo adicional de 20%