Exercise improves intestinal IgA production by T-dependent cell pathway in adults but not in aged mice.

Introduction: Hypermutated high-affinity immunoglobulin A (IgA), neutralizes toxins and drives the diversification of bacteria communities to maintain intestinal homeostasis although the mechanism underlies the impact of moderate aerobic exercise (MAE) on the IgA-generation via T-dependent (TD) is not fully know. Therefore, the aim of this study was to determine the effect of long-time MAE on the production of IgA through the TD pathway in Peyer´s patches of the small intestine from aged mice. Methods: MAE protocol consisted of twenty 3-month-old (young) BALB/c mice running in an endless band at 0° inclination and a speed of 10 m/h for 5 days a week and resting 2 days on the weekend until reaching 6-month-old (adulthood, n=10) or 24-month-old (aging, n=10). Groups of young, adult, or elderly mice were included as sedentary controls (n=10/per group). At 6 or 24 months old, all were sacrificed, and small intestine samples were dissected to prepare intestinal lavages for IgA quantitation by ELISA and to obtain suspensions from Peyer´s patches (PP) and lamina propria (LP) cells for analysis of T, B, and plasma cell subpopulations by flow cytometry and mRNA analysis expression by RT-qPCR of molecular factors related to differentiation of B cells to IgA+ plasma cells, class switch recombination, and IgA-synthesis. Statistical analysis was computed with two-way ANOVA (factor A=age, factor B=group) and p<0.05 was considered for statistically significant differences. Results: Compared to age-matched sedentary control, in exercised elderly mice, parameters were either increased (IgA concentration, IL-21, IL-10 and RDH mRNA expression), decreased (α-chain mRNA, B cells, mIgA+ B cells, mIgM+ B cells and IL-4 mRNA) or unchanged (PP mIgA+ plasmablasts and LP cyt-IgA+ plasma cells). Regarding the exercised adult mice, they showed an up-modulation of IgA-concentration, mRNA expression IL-21, IL-10, and RDH and cells (PP B and T cells, mIgM+ plasmablasts and LP cyt-IgA+plasma cells). Conclusion: Our findings suggest that MAE restored the IgA production in adult mice via the TD cell pathway but does not in aged mice. Other studies are necessary to know in more detail the impact of long-time MAE on the TD pathway to produce IgA in aging.

Apocynin, an NADPH Oxidase Enzyme Inhibitor, Prevents Amebic Liver Abscess in Hamster.

Amebiasis is an intestinal infection caused by Entamoeba histolytica. Amebic liver abscess (ALA) is the most common extraintestinal complication of amebiasis. In animal models of ALA, neutrophils have been shown to be the first cells to come into contact with Entamoeba histolytica during the initial phase of ALA. One of the multiple mechanisms by which neutrophils exhibit amebicidal activity is through reactive oxygen species (ROS) and the enzyme NADPH oxidase (NOX2), which generates and transports electrons to subsequently reduce molecular oxygen into superoxide anion. Previous reports have shown that ROS release in the susceptible animal species (hamster) is mainly stimulated by the pathogen, in turn provoking such an exacerbated inflammatory reaction that it is unable to be controlled and results in the death of the animal model. Apocynin is a natural inhibitor of NADPH oxidase. No information is available on the role of NOX in the evolution of ALA in the hamster, a susceptible model. Our study showed that administration of a selective NADPH oxidase 2 (NOX2) enzyme inhibitor significantly decreases the percentage of ALA, the size of inflammatory foci, the number of neutrophils, and NOX activity indicated by the reduction in superoxide anion (O2-) production. Moreover, in vitro, the apocynin damages amoebae. Our results showed that apocynin administration induces a decrease in the activity of NOX that could favor a decrease in ALA progression.

LDH-A Promotes Metabolic Rewiring in Leucocytes from the Intestine of Rats Treated with TNBS.

Although the aetiology of inflammatory bowel diseases (IBDs) is still unknown, one of their main characteristics is that the immune system chronically affects the permeability of the intestinal lamina propria, in turn altering the composition of the microbiota. In this study, the TNBS rat model of colitis was used because it contains a complex inflammatory milieu of polymorphonuclear cells (PMN) and lymphocytes infiltrating the lamina propria. The aim of the present study was to investigate six dehydrogenases and their respective adaptations in the tissue microenvironment by quantifying enzymatic activities measured under substrate saturation conditions in epithelial cells and leukocytes from the lamina propria of rats exposed to TNBS. Our results show that in the TNBS group, an increased DAI score was observed due to the presence of haemorrhagic and necrotic areas in the colon. In addition, the activities of G6PDH and GADH enzymes were significantly decreased in the epithelium in contrast to the increased activity of these enzymes and increased lactate mediated by the LDH-A enzyme in leukocytes in the lamina propria of the colon. Over the past years, evidence has emerged illustrating how metabolism supports aspect of cellular function and how a metabolic reprogramming can drive cell differentiation and fate. Our findings show a metabolic reprogramming in colonic lamina propria leukocytes that could be supported by increased superoxide anion.

In Vitro Evaluation of the Antiamoebic Activity of Kaempferol against Trophozoites of Entamoeba histolytica and in the Interactions of Amoebae with Hamster Neutrophils.

Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that can eliminate E. histolytica. Flavonoids are polyphenolic compounds that have demonstrated inhibition of growth and dysregulation of amoebic proteins. Despite the knowledge acquired to date, action mechanisms are not completely understood. The present work evaluates the effect of kaempferol against E. histolytica trophozoites and in the interactions with neutrophils from hamster, which is a susceptibility model. Our study demonstrated a significant reduction in the amoebic viability of trophozoites incubated with kaempferol at 150 µM for 90 min. The gene expression analysis showed a significant downregulation of Pr (peroxiredoxin), Rr (rubrerythrin), and TrxR (thioredoxin reductase). In interactions with amoebae and neutrophils for short times, we observed a reduction in ROS (reactive oxygen species), NO (nitric oxide), and MPO (myeloperoxidase) neutrophil activities. In conclusion, we confirmed that kaempferol is an effective drug against E. histolytica through the decrease in E. histolytica antioxidant enzyme expression and a regulator of several neutrophil mechanisms, such as MPO activity and the regulation of ROS and NO.

Premedication with midazolam in low-risk surgery in children does not reduce postoperative delirium. Prospective cohort study

Introduction: Pediatric postoperative delirium is a frequent complication for which preventive pharmacological measures have been suggested. The use of midazolam as a prophylactic strategy has not yet been thoroughly assessed. Notwithstanding the fact that it is used in pediatric presurgical separation anxiety, its role in delirium is yet to be established. Objective: To quantify the incidence of pediatric postoperative delirium in patients undergoing low risk surgical interventions, exposed to oral midazolam-based premedication and to explore the protective and risk factors associated with the development of delirium. Methods: Prospective, analytical observational study with a cohort design. Children were conveniently selected in accordance with the daily list of surgical procedures in the operating rooms. The inclusion criteria were children between 2 and 10 years old, ASA I-II, undergoing low risk surgeries. Concurrent and longitudinal follow-up was then conducted upon admission to the post-anesthesia care unit (PACU) for the first hour. Results: A total of 518 children were included. The overall incidence of delirium was 14.4 % (95 % CI: 11.4 %-17.5 %). In the subgroup exposed to midazolam, 178 children were analyzed, with an incidence of delirium of 16.2% (95% CI of 10,8 %-21,7). These patients exhibited a higher tendency to delirium with the use of sevoflurane or fentanyl, and/orwhen presenting with severe postoperative pain. Patients exposed to propofol and/or remifentanil showed lower incidences. Conclusions: No reduction in the incidence of emergency pediatric delirium associated with the use of pre-surgical oral midazolam in low risk surgical procedures. Prospective controlled trials and additional research are required to study the effectiveness and safety of this intervention.

Introducción: El delirio pediátrico posoperatorio es una complicación frecuente para la cual se han sugerido medidas farmacológicas de prevención. El uso de midazolam como estrategia profiláctica aún no ha sido suficientemente evaluado. A pesar de que se emplea para la ansiedad de separación pediátrica prequirúrgica, su papel en delirio aún no se ha establecido. Objetivo: Cuantificar la incidencia de delirio pediátrico posoperatorio en pacientes sometidos a cirugías de bajo riesgo quirúrgico, expuestos a premedicación basada en midazolam oral y adicionalmente, explorar los factores protectores y de riesgo asociados a la ocurrencia. Materiales y métodos: Estudio observacional analítico prospectivo con un diseño de cohorte. Se seleccionaron niños por conveniencia de acuerdo con la lista quirúrgica diaria en salas de cirugía. Como criterios de inclusión se tomaron sujetos entre 2 y 10 años de edad, ASA 1-11, sometidos a cirugías de bajo riesgo quirúrgico. Posteriormente se realizó seguimiento concurrente y longitudinal al ingreso a la unidad de recuperación posanestésica (UCPA) durante la primera hora de estancia. Resultados: Se incluyeron 518 niños. La incidencia global de delirio fue del 14,4 % (IC 95 %;11,4 %-17,5 %). En el subgrupo expuesto a midazolam se analizaron 178 niños, quienes presentaron una incidencia de delirio del 16,2 % (IC 95 %;10,8 %-21,7 %). Estos pacientes presentaron una mayor tendencia a delirio con el uso de sevofluorano o fentanilo, y/o cuando presentaron dolor severo posoperatorio. Pacientes con exposición a propofol y/o remifentanilo exhibieron incidencias inferiores. Conclusiones: No se encontró una reducción en la incidencia de delirio pediátrico de emergencia asociada al empleo de midazolam oral prequirúrgico en cirugías de bajo riesgo. Se requieren estudios prospectivos controlados e investigación adicional para el estudio de la efectividad y seguridad de esta intervención.

Outcomes of nicotinic modulation on markers of intestinal IgA antibody response.

Acetylcholine (ACh), as a ligand of nicotinic acetylcholine receptors (nAChRs), plays a key role in the cholinergic anti-inflammatory pathway; however, its role in the immunoglobulin A (IgA) response remains unknown. Therefore, the present study aimed to investigate the role of ACh in the intestinal biomarkers involved in IgA synthesis and the polymeric immunoglobulin receptor (pIgR) involved in IgA transcytosis. Groups of mice were administered GTS-21 (an α7nAChR agonist) or mecamylamine (a non-selective nAChR antagonist) intraperitoneally for 7 days. Intestinal fluids were used for antibody concentration assessment by ELISA, cell suspensions from Peyer's patches and the lamina propria were obtained for flow cytometric analysis of plasma cells, and CD4+ T-cells expressing intracellular transforming growth factor (TGF)-ß and IgA-producing interleukin (IL)-4, -5, -6 and -10, and isolated epithelial cells to determine the levels of pIgR mRNA using reverse transcription-quantitative PCR. Regarding to the untreated control group, the concentration of IgA was reduced in the mecamylamine group and unaltered in the GTS-21 group while IgM levels exhibited no differences; the percentage of IgA+ plasma cells from Peyer's patches and the lamina propria, and the percentage of TGF-ß+/CD4+ T-cells from Peyer's patches were greater in the GTS-21-group. In both treatment groups, the percentages of IgM+ plasma cells and IL-6+/IL-10+ CD4+ T cells were greater in both compartments; pIgR mRNA expression levels decreased in epithelial cells. The percentage of IL-4 CD4+ T-cells were greater in Peyer's patches and lower in the lamina propria in the mecamylamine group, and the percentage of IL-5 CD4+ T-cells in the lamina propria were decreased in both treatment groups. These findings require further examination to address the impact of cholinergic modulation on IgA-transcytosis via pIgR. The present study may be an experimental reference for clinical trials that address the role of nicotinic system in intestinal dysfunctions as postoperative ileus.

The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review.

Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis.

Cholecystokinin Outcome on Markers of Intestinal IgA Antibody Response.

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA+ B lymphocytes and IgA+ plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA+ plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-ß (TGF-ß) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA+ B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA+ B cells and α chain mRNA needs further examination.

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909 patients; follow-up <12 months) that compared web-based interventions, mobile applications, and different telemedicine platforms with SoC (clinic-based encounters). Although overall disease activity and risk of relapse were comparable between digital health technologies and SoC (very low certainty of evidence), digital health interventions were associated with lower rate of health care utilization and health care costs (low certainty of evidence). Digital health interventions did not significantly improve patients' QoL and treatment adherence compared with SoC (very low certainty of evidence). Trials may have intrinsic selection bias due to nature of digital interventions. DISCUSSION: Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Muscarinic receptors control markers of inflammation in the small intestine of BALB/c mice.

Muscarinic-acetylcholine-receptors (mAChRs) modulate intestinal homeostasis, but their role in inflammation is unclear; thus, this issue was the focus of this study. BALB/c mice were treated for 7 days with muscarine (mAChR/agonist), atropine (mAChR/antagonist) or saline. Small-intestine samples were collected for histology and cytofluorometric assays in Peyer's patches (PP) and lamina propria (LP) cell-suspensions. In LP, goblet-cells/leukocytes/neutrophils/MPO+ cells and MPO/activity were increased in the muscarine group. In PP, IFN-γ+/CD4+ T or IL-6+/CD4+ T cell numbers were higher in the muscarine or atropine groups, respectively. In LP, TNF-α+/CD4+ T cell number was higher in the muscarine group and lower in the atropine.

CD4+/IL­4+ lymphocytes of the lamina propria and substance P promote colonic protection during acute stress.

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus­pituitary­adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine­producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin­1 expression and an elevation in E­cadherin expression during acute stress. Increased E­cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti­inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL­6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.

Diversity of effects induced by boron-containing compounds on immune response cells and on antibodies in basal state.

BACKGROUND: It has been reported that boron induces changes in the immune response, including in inflammatory processes. Recently, the effect of boric acid has been documented on the differentiation of lymphocyte clusters in mice and rats. However, the differences among boron-containing compounds (BCC) have been poorly explored. METHODS: In this study, we analyzed the effects after oral administration of boric acid (BOR), methylboronic (MET), 3-thyenylboronic (3TB), 4-hydroxymethyl-phenylboronic (4MP) and 4-methanesulfonyl-phenylboronic (4SP) acids on the populations of lymphocytes from spleen and Peyer's patch (PP) as well as on antibodies. Groups of six male BALB/c were orally treated with 4.6 mg/kg of body weight with BOR, MET, 3TB, 4MP, and 4SP/daily for 10 days or vehicle (VEH) as a control group. After euthanasia, the spleen and small intestine were dissected. We conducted flow cytometry assays to assess B, CD3+ T, CD4+ T, and CD8+ T cells. Levels of IgG and IgM in serum, and IgA in intestinal fluid samples were analyzed by enzyme immunoassay. RESULTS: In particular, we observed the effects of the administration of boronic acids on the number of lymphocytes; these changes were more notable in spleen than in PP. We found different profiles for each boron-containing compound, that is BOR induced an increase in the percentage of CD8+ T and CD19+/IgA+ cells in spleen, but a decrease in CD8+ T and B220+/CD19+ cells in PP. Meanwhile MET induced a decrease of CD4+ T in spleen, but induced an increase of CD4+ T cells and a decrease in the number of CD8+ T cells in PP. Boronic acids with an aromatic ring moiety induced changes in serum immunoglobulins levels, while 3TB acid induced a notable increase in S-IgA. CONCLUSIONS: Effects in lymphocyte populations and antibodies are different for each tested compound. These results highlight the establishment of the necessary structure-activity relationship for BCC as immunomodulatory drugs. This is relevant in the biomedical field due to their attractiveness for selecting compounds to develop therapeutic tools.

Temporal Dynamics of T Helper Populations in the Proximal Small Intestine after Oral Bovine Lactoferrin Administration in BALB/c Mice.

Bovine lactoferrin (bLf), a component of milk and a dietary supplement, modulates intestinal immunity at effector and inductor sites. Considering the regional difference in intestinal compartments and the dynamics of local cytokine-producing cells in the gut across time, the aim of this work was to characterize the effects of bLf on the proximal small intestine in a BALB/c murine model of oral administration. Male BALB/c mice were treated with oral bLf vs. saline control as mock by buccal deposition for 28 days. Intestinal secretions were obtained at different time points and cells were isolated from Peyer's patches (PP) and lamina propria (LP) of the proximal small intestine as representative inductor and effector sites, respectively. Total and specific anti-bLF IgA and IgM were determined by enzyme-immuno assay; the percentages of IgA+ and IgM+ plasma cells (PC) and cytokine-producing CD4+ T cells of PP and LP were analyzed by flow cytometry. We found that total and bLf-specific IgA and IgM levels were increased in the intestinal secretions of the bLf group in comparison to mock group and day 0. LP IgA+ PC and IgM+ PC presented an initial elevation on day 7 and day 21, respectively, followed by a decrease on day 28 in comparison to mock. Higher percentages of CD4+ T cells in LP were found in the bLf group. Cytokines-producing CD4+ T cells populations presented a pattern of increases and decreases in the bLf group in both LP and PP. Transforming growth factor beta (TGF-ß)+ CD4+ T cells showed higher percentages after bLf administration with a marked peak at day 21 in both LP and PP in comparison to mock-treated mice. Oral bLf exhibits complex immune properties in the proximal small intestine, where temporal monitoring of the inductor and effector compartments reveals patterns of rises and falls of different cell populations. Exceptionally, TGF-ß+ CD4+ T cells show consistent higher numbers after bLf intervention across time. Our work suggests that isolated measurements do not show the complete picture of the modulatory effects of oral bLf in immunological sites as dynamic as the proximal small intestine.

Determinación de contactos cercanos con riesgo de transmisión durante las medidas de cuarentena y distanciamiento social para el Covid-19 en personal de salud / Determination of close contacts at risk of transmission during quarantine and social stating measures for Covid-19 in health personnel

El personal de salud por su ámbito laboral sanitario es de alto riesgo para la adquisición y transmisión de la infección por Covid-19. Los contactos cercanos del personal de salud fuera del ambiente hospitalario son frecuentes y variados. El objeto de la investigación es determinar la frecuencia de contactos cercanos para infecciones Covid-19 del personal de salud en su ambiente sanitario,social y familiar previo y durante la pandemia marzo y abril 2020. Métodos: Estudio de corte transversal por cuestionario auto administrado por vía digital dirigido al personal de salud. La población objeto son profesionales activos adscritos a Sociedades Científicas y la UCV. Variables demográficas: edad, sexo,año académico, cohabitante y los contactos cercanos durante traslados, actividades académicas, hospitalarias y sociales.Medidas de tendencia central y dispersión, distribuciones de frecuencia y figuras. Chi cuadrado e intervalos de confianza al 95%, medidas de correlación, comparación con t con error al fade 0,05. Resultados: 194 trabajadores de la salud completaron la encuesta, Sexo femenino 124 (63,9%), edad promedio 49,6 y mediana 53 años. La gran mayoría médicos 88,6%. Se dedican a actividades asistenciales 81%. El promedio de contactos diarios del personal de salud es 38. Los contactos intrahospitalario promedio diario son la mayoría 71%, (27,1 contactos/día). De estos con colegas 5,6, con enfermeras y paraclínicos 3,7; otro personal 4,7; pacientes y sus familiares 7,5 y 5,4. Conclusión:El personal de salud tiene un alto número de contactos cercanos diarios para la transmisión de infecciones respiratorias agudas,lo que representa un alto riesgo para adquirir y son potenciales dispersores de las infecciones a familiares y sociales(AU)

Introduction: Health workers are at high risk for the acquisition and transmission of Covid-19 infection. Close contacts of health workers outside the hospital environment are frequent and varied. The objective of the investigation is to determine the frequency of close contacts for COVID-19 infections of health workers in their previous health, social and family environment and during the pandemic. Methodology: Cross-sectional study by self-administered digital questionnaire to health workers. The target were active professionals of Scientific Societies and professionals of UCV. Demographic variables: age, gender, academic year, cohabitant and close contacts during transfers, academics, hospitals and social. Analysis of central trend and dispersion measures, presentationof data in frequency distributions and bar charts, and segment diagrams. Chi squared, confidence intervals to 95%, correlation measures, comparison with t with alpha error of 0.05 was calculated. Results: 194 health workers participants, most female 124 (63.9%), average age 49.6 and median 53 years.The majority were doctors 88.6%. 81% are dedicated to welfare activities. The average daily contact of health workers is 38people. The average daily hospital contacts are the majority 71%, average of 27.1. Average daily contacts with colleagues 5.6,with nurses and paraclinical 3.7; other personnel 4.7; patientsand their families 7.5 and 5.4. Conclusion: Health workers are highly exposed to infectious respiratory diseases due to their high frequency of close contacts in their daily routine. Therefore, Health workers are potential dispersants of infections to family members, friends and others(AU)

Tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl)carbamate Has Moderated Protective Activity in Astrocytes Stimulated with Amyloid Beta 1-42 and in a Scopolamine Model.

Alzheimer's disease (AD) is a neurodegenerative disease with no cure nowadays; there is no treatment either to prevent or to stop its progression. In vitro studies suggested that tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl) carbamate named the M4 compound can act as both ß-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Aß) aggregation and the formation of fibrils (fAß) from Aß1-42. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aß1-42 could be prevented. Second, our work investigated the ability of the M4 compound to inhibit amyloidogenesis using an in vivo model after scopolamine administration. The results showed that M4 possesses a moderate protective effect in astrocytes against Aß1-42 due to a reduction in the TNF-α and free radicals observed in cell cultures. In the in vivo studies, however, no significant effect of M4 was observed in comparison with a galantamine model employed in rats, in which case this outcome was attributed to the bioavailability of M4 in the brain of the rats.

De la fisiología al ventilador, interacción corazón pulmón durante la ventilación mecánica / From physiology to ventilator, heart lung interaction during mechanical ventilation / Da fisiologia ao ventilador, interação coração pulmão durante ventilação mecânica

Resumen: La interacción corazón-pulmón fue observada por Hales desde el siglo XVIII. Este sistema funciona de forma simple como un circuito y una bomba. Al ocupar un mismo espacio físico: la caja torácica; los cambios de presión dentro de ésta afectarán el sistema formado por el corazón y el pulmón. Durante el ciclo respiratorio, la presión torácica varía, afectando el gradiente de presión de sangre que entra y sale del tórax. Cada uno de los componentes de la precarga como de la postcarga deben estudiarse por separado, para posteriormente entender la interdependencia del ventrículo derecho como izquierdo y su repercusión en la circulación pulmonar. La ventilación con presión positiva eleva la presión intratorácica, condiciona la disminución del llenado del ventrículo derecho, condiciona un aumento de la postcarga del mismo y reduce el flujo sanguíneo pulmonar. Todos los cambios que se presentan durante la ventilación mecánica pueden desencadenar en inestabilidad hemodinámica. El ventrículo derecho, al tener sus resistencias vasculares y precarga reducidas, está sometido particularmente a estos cambios. El volumen tidal disminuido, entre otras estrategias, se emplea con la finalidad de reducir los efectos mecánicos que sufre el ventrículo derecho.

Abstract: The heart-lung interaction was observed by Hales since the 18th century. This system works simply as a circuit and a pump. By occupying the same physical space: the rib cage, changes in pressure within it will affect the system formed by the heart and lung. During the respiratory cycle the thoracic pressure varies, affecting the blood pressure gradient that enters and leaves the chest. Each of the components of the preload and afterload should be studied separately. To later understand the interdependence of the right ventricle as left and its impact on the pulmonary circulation. Ventilation with positive pressure increases intrathoracic pressure, determines decreased filling of the right ventricle, conditioning an increase in its afterload and decreasing pulmonary blood flow. All changes that occur during mechanical ventilation can trigger hemodynamic instability. The right ventricle having its reduced vascular resistance and preload is particularly subject to these changes. The use of a reduced tidal volume among other strategies, are used in order to reduce the mechanical effects suffered by the right ventricle.

Resumo: A interação coração-pulmão foi observada por Hales desde o século XVIII. Este sistema funciona simplesmente como um circuito e uma bomba. Por ocupar o mesmo espaço físico: a caixa torácica, as mudanças de pressão dentro dela afetarão o sistema formado pelo coração e pulmão. Durante o ciclo respiratório, a pressão torácica varia afetando o gradiente de pressão do sangue que entra e sai do tórax. Cada um dos componentes de pré-carga e pós-carga deve ser estudado separadamente. Para posteriormente entender a interdependência dos ventrículos direito e esquerdo e seu impacto na circulação pulmonar. A ventilação com pressão positiva aumenta a pressão intratorácica, diminui o enchimento do ventrículo direito, condiciona o aumento da sua pós-carga e diminui o fluxo sanguíneo pulmonar. Todas as alterações que ocorrem durante a ventilação mecânica podem levar à instabilidade hemodinâmica. O ventrículo direito, tendo sua resistência vascular e pré-carga reduzidas, está particularmente sujeito a essas alterações. A utilização da diminuição do volume corrente, entre outras estratégias, é utilizada para diminuir os efeitos mecânicos sofridos pelo ventrículo direito.

Chronic Administration of Scopolamine Increased GSK3ßP9, Beta Secretase, Amyloid Beta, and Oxidative Stress in the Hippocampus of Wistar Rats.

The increase of amyloid beta (Aß) release and hyperphosphorylation of Tau protein represents the main events related to Alzheimer's disease (AD). Furthermore, the sporadic type represents the most common form of AD. Therefore, the establishment of a non-transgenic animal model that resembles the characteristics of the disease is of particular importance. Scopolamine has been linked to increases in both Aß production and oxidative stress in rat and mice brains. Thus, the purpose of the present work was to identify changes in biomarkers that are related to AD after chronic administration of scopolamine (2 mg/kg i.p., during 6 and 12 weeks) to male Wistar rats. The results showed increased Aß deposition at rat hippocampus which could be due to an increase of ß-site amyloid-ß-protein precursor cleaving enzyme 1 (BACE1) expression and activity. These findings could be related to the increase of glycogen synthase kinase 3 phosphorylated (GSK3ßP9) expression. Finally, the establishment of a state of oxidative stress in groups treated with scopolamine was demonstrated by an increase in free radical content and MDA levels. The present study facilitates our understanding of the changes that occur in biomolecules related to AD in Wistar rats after the chronic administration of scopolamine.

Anterior subdiaphragmatic vagotomy decreases the IgA antibody response in the small intestines of BALB/c mice.

To assess the impact of vagotomy on the IgA-response, male BALB/c mice underwent anterior vagotomy or a sham procedure were sacrificed on day 14 post-operation and the proximal and distal small-gut segments were dissected. In intestinal lavages IgA/IgM antibodies were analysed by ELISA; in Peyer's-patches and lamina-propria cell suspensions the intracellular IgA-associated interleukins (ILs) and pro-inflammatory cytokines in CD4+ T cells were analysed by cytofluorometry. Vagotomy reduced the IgA or increased the IgM antibody concentration in both segments and reduced or increased the lamina- propria CD4+ T cell pro-inflammatory cytokine responses in the distal or proximal segments, respectively. Data show the role of the vagus nerve on the IgA response.

Dialyzable Leukocyte Extract (Transferon™) Administration in Sepsis: Experience from a Single Referral Pediatric Intensive Care Unit.

Immunomodulatory agents have been proposed as therapeutic candidates to improve outcomes in sepsis. Transferon™, a dialyzable leukocyte extract (DLE), has been supported in Mexico as an immunomodulatory adjuvant in anti-infectious therapy. Here we present a retrospective study describing the experience of a referral pediatric intensive care unit (PICU) with Transferon™ in sepsis. We studied clinical and laboratory data from 123 patients with sepsis (15 in the DLE group and 108 in the control group) that were admitted to PICU during the period between January 2010 and December 2016. Transferon™ DLE use was associated with lower C reactive protein (CRP), increase in total lymphocyte counts (TLC), and decrease in total neutrophil count (TNC) 72 hours after Transferon™ DLE administration. The control group did not present any significant difference in CRP values and had lower TLC after 72 hours of admission. There was no difference in PICU length of stay between control and Transferon™ DLE group. Transferon™ DLE administration was associated with a higher survival rate at the end of PICU stay. This study shows a possible immunomodulatory effect of Transferon™ on pediatric sepsis patients.

Effects of boron-containing compounds on immune responses: review and patenting trends.

INTRODUCTION: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system. AREAS COVERED: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms. EXPERT OPINION: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure-activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.