The effects of Pyrantel-Oxantel on the Dipylidium caninum tapeworm: An in vitro study

El presente estudio tuvo como objetivo evaluar, in vitro, el efecto cestocida de Pirantel-Oxantel en la tenia Dipylidium caninum. Cada muestra de intestino se obtuvo mediante una incisión transversal de la zona abdominal de cada sujeto canino sacrificado, se diseccionó individualmente a través de una incisión longitudinal y se examinó para detectar la presencia de D. caninum. Se utilizó un microscopio óptico para identificar y verificar la morfología y viabilidad de la proglótide en función de su aspecto macroscópico. Los efectos cestocidas de Pirantel-Oxantel (75 mg de pamoato de pirantel; 75 mg de pamoato de oxantel) se evaluaron en tenias adultas (grupo tratado, n= 21; grupo testigo, n= 21) colocadas en placas de Petri e incubadas a 37 °C. Una hora postincubación, los cestodos D. caninum tratados con Pirantel-Oxantel presentaron una disminución del 28 % (P= 0.001) en la motilidad, la cual aumentó a una disminución del 52 % (P=0.0001) al final de la segunda hora. El grupo testigo (P= 0.0001) presentó un 55.7 % de motilidad durante al menos las primeras 6 h de incubación y 4.2 % (P= 0.001) de motilidad al final del estudio, mientras que en el grupo tratado se observó un 0 % de motilidad al final del estudio. El Pirantel-Oxantel tuvo un efecto letal (P= 0.0001) en el adulto de D. caninum, con una mortalidad del 100 % observada 6 h después de la postincubación in vitro, mientras que el grupo de control presentó un 55.7 % de viabilidad después del mismo periodo. Además, el Pirantel-Oxantel redujo (P= 0.001) el grosor del tegumento en 42.5 % (10.24 ± 0.21 μm), mientras que éste fue de 17.81 ± 0.33 μm para el grupo testigo. Los resultados de este estudio indican que el Pirantel-Oxantel tiene un efecto terapéutico en la presencia de D. caninum, induciendo tanto una disminución del grosor del tegumento como un aumento de la mortalidad.The present study aimed to evaluate, in vitro, the cestocidal effect of Pyrantel-Oxantel on the Dipylidium caninum tapeworm. Each intestine sample was obtained by means of a transversal incision of the abdominal area of each euthanized canine subject, individually dissected via  longitudinal incision, and examined for the presence of D. caninum. An optical microscope was used to identify and verify proglottid morphology and viability based on its macroscopic appearance. The cestocidal effects of Pyrantel-Oxantel (75 mg pyrantel pamoate; 75 mg oxantel pamoate) were assessed in adult tapeworms (treated group, n= 21; control group, n= 21) placed on Petri dishes and incubated at 37 °C. One-hour post-incubation, the D. caninum cestodes treated with Pyrantel-Oxantel presented a 28 % decrease (P=0.001) in motility, which rose to a 52 % (P=0.0001) decrease by the end of the second hour. The control group (P=0.0001) presented 55.7 % motility for at least the first six hours of incubation and 4.2 % (P=0.001) motility by the end of the study, while 0 % motility was observed in the treated group by the end of the study. Pyrantel-Oxantel had a lethal effect (P=0.0001) on adult D. caninum, with 100 % mortality observed 6 h after in vitro post-incubation, while the control group presented 55.7 % viability after the same time period. In addition, Pyrantel-Oxantel reduced (P=0.001) tegument thickness by 42.5 % (10.24 ± 0.21 µm), while this was 17.81 ± 0.33 µm for the control group. The results of this study indicate that Pyrantel-Oxantel has a therapeutic effect on the presence of D. caninum, inducing both a reduction of the tegument thickness and increased mortality

Consenso de inmunizaciones en adultos con enfermedades reumáticas inflamatorias crónicas autoinmunes

Aumento del riesgo de infecciones prevenibles y sus complicaciones en pacientes con enfermedades reumáticas inflamatorias crónicas (ERICA), con y sin tratamiento con inmunosupresores (IS), y beneficios de la vacunación

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

Altres ajuts: Fundació La Marató de TV3 2016 (303/C/2016) (201602.31) (to J.J.) and (97/C/2016) (201605-31) (to A.F.V.).The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation

Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARα, β/δ, and γ

PPARα, β/δ, and γ regulate genes involved in the control of lipid metabolism and inflammation and are expressed in all major cell types of atherosclerotic lesions. In vitro studies have suggested that PPARs exert antiatherogenic effects by inhibiting the expression of proinflammatory genes and enhancing cholesterol efflux via activation of the liver X receptor–ABCA1 (LXR-ABCA1) pathway. To investigate the potential importance of these activities in vivo, we performed a systematic analysis of the effects of PPARα, β, and γ agonists on foam-cell formation and atherosclerosis in male LDL receptor–deficient (LDLR(–/–)) mice. Like the PPARγ agonist, a PPARα-specific agonist strongly inhibited atherosclerosis, whereas a PPARβ-specific agonist failed to inhibit lesion formation. In concert with their effects on atherosclerosis, PPARα and PPARγ agonists, but not the PPARβ agonist, inhibited the formation of macrophage foam cells in the peritoneal cavity. Unexpectedly, PPARα and PPARγ agonists inhibited foam-cell formation in vivo through distinct ABCA1-independent pathways. While inhibition of foam-cell formation by PPARα required LXRs, activation of PPARγ reduced cholesterol esterification, induced expression of ABCG1, and stimulated HDL-dependent cholesterol efflux in an LXR-independent manner. In concert, these findings reveal receptor-specific mechanisms by which PPARs influence macrophage cholesterol homeostasis. In the future, these mechanisms may be exploited pharmacologically to inhibit the development of atherosclerosis

The Epidemiology of Mould Infections in Argentina: Review and Experience

Fil: Dignani, María Cecilia. Registro Micosis Invasoras (REMIIN), Yerbal 315, App 2B., C1405CDG, Ciudad Autónoma de Buenos Aires (CABA); ArgentinaFil: Davel, Graciela Odelsia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Refojo, Nicolás. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Mazza, Mariana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Córdoba, Susana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Hevia, Alejandra I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Abrantes, Ruben Antonio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Isla, Guillermina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Fernández, Julián. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rivas, María C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Valledor, Alejandra. Hospital Italiano, Juan D. Perón 4190, CABA; ArgentinaFil: Laborde, Ana. Fundaleu (Fundación de Lucha contra la Leucemia), Uriburu 1450, C1114AAN, CABA; ArgentinaFil: Pereyra, María Laura. Hospital Universitario Austral, Pilar, Bs. As.; Argentina.Fil: Roccia Rossi, Inés. Hospital Gral. San Martín, La Plata; Argentina.Fil: Red Nacional de Laboratorios de Micología; Argentina.Fil: Participantes del Programa Nacional de Control de Calidad en Micología; Argentina.Fil: Registro de Micosis Invasoras; Argentina.During the last decades, there has been an increasing proportion of patients susceptible to invasive fungal disease (IFD). The epidemiology of IFD varies mainly due to geography, antifungal exposure, and nosocomial reservoirs. We reviewed the Argentinean epidemiology of invasive mold disease (IMD) by analyzing laboratory and clinical data. Invasive mold disease was the second most prevalent IFD following the yeasts, with a prevalence that ranged from 0.98 to 1.31/100,000 population. The majority (60–85 %) of IMD was caused by hyalohyphomycetes followed by Mucorales (6–21 %) and phaeohyphomycetes (7–13 %). The most prevalent genera were Aspergillus (40–67 % of IMD) followed by Fusarium (10–14 %). The most prevalent species were A. fumigatus (38–50 %) followed by A. flavus (27–43 %). In immunocompromised patients in Argentina the most prevalent agents of IMD are Aspergillus, followed by Fusarium and Mucoral

The Epidemiology of Mould Infections in Argentina: Review and Experience

Fil: Dignani, María Cecilia. Registro Micosis Invasoras (REMIIN), Yerbal 315, App 2B., C1405CDG, Ciudad Autónoma de Buenos Aires (CABA); ArgentinaFil: Davel, Graciela Odelsia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Refojo, Nicolás. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Mazza, Mariana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Córdoba, Susana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Hevia, Alejandra I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Abrantes, Ruben Antonio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Isla, Guillermina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Fernández, Julián. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rivas, María C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Valledor, Alejandra. Hospital Italiano, Juan D. Perón 4190, CABA; ArgentinaFil: Laborde, Ana. Fundaleu (Fundación de Lucha contra la Leucemia), Uriburu 1450, C1114AAN, CABA; ArgentinaFil: Pereyra, María Laura. Hospital Universitario Austral, Pilar, Bs. As.; Argentina.Fil: Roccia Rossi, Inés. Hospital Gral. San Martín, La Plata; Argentina.Fil: Red Nacional de Laboratorios de Micología; Argentina.Fil: Participantes del Programa Nacional de Control de Calidad en Micología; Argentina.Fil: Registro de Micosis Invasoras; Argentina.During the last decades, there has been an increasing proportion of patients susceptible to invasive fungal disease (IFD). The epidemiology of IFD varies mainly due to geography, antifungal exposure, and nosocomial reservoirs. We reviewed the Argentinean epidemiology of invasive mold disease (IMD) by analyzing laboratory and clinical data. Invasive mold disease was the second most prevalent IFD following the yeasts, with a prevalence that ranged from 0.98 to 1.31/100,000 population. The majority (60–85 %) of IMD was caused by hyalohyphomycetes followed by Mucorales (6–21 %) and phaeohyphomycetes (7–13 %). The most prevalent genera were Aspergillus (40–67 % of IMD) followed by Fusarium (10–14 %). The most prevalent species were A. fumigatus (38–50 %) followed by A. flavus (27–43 %). In immunocompromised patients in Argentina the most prevalent agents of IMD are Aspergillus, followed by Fusarium and Mucoral

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.Fil: Herrera, Fabián. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Torres, Diego. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Laborde, Ana. Fundación Para Combatir la Leucemia; ArgentinaFil: Berruezo, Lorena. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Jordán, Rosana. Hospital Británico de Buenos Aires; ArgentinaFil: Roccia Rossi, Inés. Hospital International General Acute Gral San Martin; ArgentinaFil: Valledor, Alejandra. Hospital Italiano; ArgentinaFil: Costantini, Patricia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Dictar, Miguel. Instituto Alexander Fleming; ArgentinaFil: Nenna, Andrea. Fundacion Marie Curie;Fil: Pereyra, María Laura. Universidad Austral; ArgentinaFil: Lambert, Sandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Benso, José. Hospital Italiano; ArgentinaFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Gonzalez Ibañez, María Luz. Fundación Para Combatir la Leucemia; ArgentinaFil: Baldoni, Nadia. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Eusebio, María José. Hospital Británico de Buenos Aires; ArgentinaFil: Lovano, Fiorella. Hospital International General Acute Gral San Martin; ArgentinaFil: Barcán, Laura. Hospital Italiano; ArgentinaFil: Luck, Martín. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Racioppi, Agustina. Instituto Alexander Fleming; ArgentinaFil: Tula, Lucas Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Pasterán, Fernando. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Corso, Alejandra. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Rapoport, Melina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Nicola, Federico. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: García Damiano, María Cristina. Fundación Para Combatir la Leucemia; ArgentinaFil: Carbone, Ruth. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Monge, Renata. Hospital Británico de Buenos Aires; ArgentinaFil: Reynaldi, Mariana. Hospital International General Acute Gral San Martin; ArgentinaFil: Greco, Graciela. Hospital Italiano; ArgentinaFil: Bronzi, Marcelo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Valle, Sandra. Instituto Alexander Fleming; ArgentinaFil: Chaves, María Laura. Fundacion Marie Curie;Fil: Vilches, Viviana. Universidad Austral; ArgentinaFil: Blanco, Miriam Edith. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Carena, Alberto Ángel. Centro de Educación Medica E Invest.clinicas; Argentin

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.status: publishe