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El objetivo fue diagnosticar el comportamiento de la población en el Perú sobre el consumo de bolsas de plástico de un solo uso. Para la encuesta se utilizó un cuestionario semiestructurado de 26 preguntas, compuesto de cuatro dimensiones: información primaria, estilos de consumo, conocimiento ambiental y tendencia al cambio. La muestra fue de 1400 personas en forma presencial y virtual durante el 2019. En relación a la información primaria, viven de tres a cinco individuos por vivienda, prevalecen personas con grado universitario y sin instrucción, compuesta por trabajadores independientes, siendo el sexo femenino el dominante, con edad de 20 a 40 años. Sobre los estilos de consumo, los encuestados realizan sus compras en mercados minoristas y en supermercados, acudiendo de una a dos veces por semana, no llevan ningún material para almacenar sus compras y reciben bolsas de plástico de estos establecimientos. Referente al conocimiento ambiental, prefieren bolsas de plástico para trasladar sus compras por no tener costo. Referente al impacto ambiental, mencionan que sí conocen, pero no cuentan con otra opción, recibiendo de seis a 10 bolsas por compra que son dispuestas para la eliminación de la basura. Finalmente, para la tendencia al cambio, prefieren que los establecimientos dejen de facilitar gratuitamente las bolsas, para no contaminar, prefiriendo que se entreguen bolsas reutilizables, y están dispuestos a pagar hasta cinco céntimos de sol por bolsa. Finalmente, se requieren políticas para orientar a los consumidores a l uso de bolsas de plástico de un solo uso. ABSTRACT The objective was to diagnose the behavior of the population in Peru regarding the consumption of single-use plastic bags. For the survey, a 26-question semi-structured questionnaire was used, made up of four dimensions: primary information, consumption styles, environmental knowledge and tendency to change. The sample was 1,400 people in person and online during 2019. In relation to primary information, 3 to 5 individuals live per home; people with a university degree and without instruction prevail, made up of independent workers, the female sex being the dominant, aged 20 to 40 years. Regarding consumption styles, respondents make their purchases in retail markets and supermarkets, coming from one to two times a week, they do not carry any materials to store their purchases and they receive plastic bags from these establishments. Regarding environmental knowledge, they prefer plastic bags to carry their purchases because they have no cost. Regarding the environmental impact, they mention that they do know, but have no other option, receiving 6 to 10 bags per purchase that are disposed of for the disposal of garbage. Finally, for the tendency to change, they prefer that the establishments stop providing the bags free of charge, so as not to contaminate, preferring that reusable bags be delivered, and they are willing to pay up to 5 cents per bag. Finally, policies are required to guide consumers to the use of single-use plastic bags. Keywords: Awareness, bags, environment, plastic, pollution, reduce, reuse.

Se diagnosticó la percepción sobre la contaminación ambiental de la publicidad objetiva de origen público y privado en el Perú. Se utilizó una encuesta semiestructurada de 20 preguntas que estuvo compuesta de tres dimensiones: información primaria, impactos y consecuencias ambientales, y medidas de control. La muestra fue de 1200 personas y se desarrolló del 20 de mayo al 06 de junio del 2019. Los encuestados consideran a los letreros por campañas políticas como la peor forma de contaminación visual. Los grafitis tienen un impacto ambiental en las ciudades, generando pésima imagen. Los letreros digitales de propaganda, generan impactos asociados con el resplandor y distracción de las personas, y los afiches son elementos contaminantes. La publicidad afecta su concentración, y les genera distracción provocándole alteración de sus sentidos, causándoles mal humor y cambios en su estado de ánimo, e incrementa sus niveles de estrés. También, consideran que la contaminación visual tiene impacto sobre su campo visual. La publicidad, genera una mala imagen. Para la dimensión de medidas de control, se muestran a favor de implementar normas legales que regulen la publicidad, acompañado de fiscalizaciones para restringir la exagerada publicidad. Las alternativas de publicidad son la digital y por redes sociales. Finalmente, se concluye que la población, considera a la publicidad, como elementos de alto impacto visual, generando consecuencias con potencial afección a su salud y al ambiente, generando mala imagen a una ciudad. La falta de normas legales y tecnologías modernas en la actualidad, genera una exacerbada publicidad en las ciudades. ABSTRACT The perception of environmental pollution from objective public and private advertising in Peru was diagnosed. A 20-question semi-structured survey was used that was composed of three dimensions: primary information, environmental impacts and consequences, and control measures. The sample was 1,200 people and ran from May 20 to June 06, 2019. Respondents consider signs for political campaigns as the worst form of visual contamination. Graffiti has an environmental impact in cities, generating a terrible image. Digital propaganda signs generate impacts associated with glare and distraction of people, and posters are polluting elements. Advertising affects their concentration, and generates distraction causing their senses to alter, causing them to be in a bad mood and changes in their mood, and increases their stress levels. Also, they consider that visual contamination has an impact on their visual field. Advertising generates a bad image. For the dimension of control measures, they are in favor of implementing legal norms that regulate advertising, accompanied by audits to restrict exaggerated advertising. Advertising alternatives are digital and through social networks. Finally, it is concluded that the population considers advertising as elements of high visual impact, generating consequences with a potential effect on their health and the environment, generating a bad image for a city. The lack of legal norms and modern technologies at present generates an exacerbated publicity in the cities. Keywords: Advertising, consequences, environment, impacts.

Con el avance de la pandemia por COVID-19, la aparición de pacientes con un segundo episodio confirmado por reacción en cadena de la polimerasa, con transcripción inversa (rt-PCR) compatible con reinfección, puso de manifiesto la falta de recomendaciones para su abordaje.Presentamos un estudio descriptivo multicéntrico retro-prospectivo de una serie de doce casos atendidos entre el 01/06/2020 y el 20/10/2020. En la misma, diez casos presentaron el segundo episodio en un período de tiempo menor a 90 días. Por su complejidad, la confirmación de una reinfección no está al alcance en la práctica diaria. Esto requiere de estudios que incluyan comparaciones genómicas de cepas virales involucradas en ambos episodios, determinación de la infectividad del ARN por cultivo viral y análisis molecular. Es necesario establecer definiciones operativas y algoritmos clínicos para la atención de los segundos episodios.

The objective was to diagnose the behavior of the population in Peru regarding the consumption of single-use plastic bags. For the survey, a 26-question semi-structured questionnaire was used, made up of four dimensions: primary information, consumption styles, environmental knowledge and tendency to change. The sample was 1,400 people in person and online during 2019. In relation to primary information, 3 to 5 individuals live per home; people with a university degree and without instruction prevail, made up of independent workers, the female sex being the dominant, aged 20 to 40 years. Regarding consumption styles, respondents make their purchases in retail markets and supermarkets, coming from one to two times a week, they do not carry any materials to store their purchases and they receive plastic bags from these establishments. Regarding environmental knowledge, they prefer plastic bags to carry their purchases because they have no cost. Regarding the environmental impact, they mention that they do know, but have no other option, receiving 6 to 10 bags per purchase that are disposed of for the disposal of garbage. Finally, for the tendency to change, they prefer that the establishments stop providing the bags free of charge, so as not to contaminate, preferring that reusable bags be delivered, and they are willing to pay up to 5 cents per bag. Finally, policies are required to guide consumers to the use of single-use plastic bags. El objetivo fue diagnosticar el comportamiento de la población en el Perú sobre el consumo de bolsas de plástico de un solo uso. Para la encuesta se utilizó un cuestionario semiestructurado de 26 preguntas, compuesto de cuatro dimensiones: información primaria, estilos de consumo, conocimiento ambiental y tendencia al cambio. La muestra fue de 1400 personas en forma presencial y virtual durante el 2019. En relación a la información primaria, viven de tres a cinco individuos por vivienda, prevalecen personas con grado universitario y sin instrucción, compuesta por trabajadores independientes, siendo el sexo femenino el dominante, con edad de 20 a 40 años. Sobre los estilos de consumo, los encuestados realizan sus compras en mercados minoristas y en supermercados, acudiendo de una a dos veces por semana, no llevan ningún material para almacenar sus compras y reciben bolsas de plástico de estos establecimientos. Referente al conocimiento ambiental, prefieren bolsas de plástico para trasladar sus compras por no tener costo. Referente al impacto ambiental, mencionan que sí conocen, pero no cuentan con otra opción, recibiendo de seis a 10 bolsas por compra que son dispuestas para la eliminación de la basura. Finalmente, para la tendencia al cambio, prefieren que los establecimientos dejen de facilitar gratuitamente las bolsas, para no contaminar, prefiriendo que se entreguen bolsas reutilizables, y están dispuestos a pagar hasta cinco céntimos de sol por bolsa. Finalmente, se requieren políticas para orientar a los consumidores a l uso de bolsas de plástico de un solo uso. ABSTRACT The objective was to diagnose the behavior of the population in Peru regarding the consumption of single-use plastic bags. For the survey, a 26-question semi-structured questionnaire was used, made up of four dimensions: primary information, consumption styles, environmental knowledge and tendency to change. The sample was 1,400 people in person and online during 2019. In relation to primary information, 3 to 5 individuals live per home; people with a university degree and without instruction prevail, made up of independent workers, the female sex being the dominant, aged 20 to 40 years. Regarding consumption styles, respondents make their purchases in retail markets and supermarkets, coming from one to two times a week, they do not carry any materials to store their purchases and they receive plastic bags from these establishments. Regarding environmental knowledge, they prefer plastic bags to carry their purchases because they have no cost. Regarding the environmental impact, they mention that they do know, but have no other option, receiving 6 to 10 bags per purchase that are disposed of for the disposal of garbage. Finally, for the tendency to change, they prefer that the establishments stop providing the bags free of charge, so as not to contaminate, preferring that reusable bags be delivered, and they are willing to pay up to 5 cents per bag. Finally, policies are required to guide consumers to the use of single-use plastic bags. Keywords: Awareness, bags, environment, plastic, pollution, reduce, reuse.

This study was conducted to investigate the effects of dietary supplementation of porcine digestible peptides (PDP), spray-dried plasma (SDP), or a combination of both, on growth performance and the expression of genes related to intestinal function of weaned pigs. A total of 180 piglets (trial 1) and 198 piglets (trial 2) were used to evaluate the partial substitution of soybean ingredients with 2% SDP or 2% PDP (trial 1), and with 3% SDP or the combination of 1% SDP and 2% PDP (SDP-PDP, trial 2) during the pre-starter period (0&ndash, 14 days). The gene expression of 56 genes was quantified in a qPCR platform in jejunum and ileum samples obtained from piglets 14 d after weaning (trial 2). Piglets fed SDP, PDP and SDP-PDP had a higher body weight (BW), average daily gain (ADG) and feed efficiency (G:F) than the soybean control on day 14 (p &lt, 0.05). In addition, the combination of SDP and PDP upregulated ten genes in jejunum samples (p &lt, 0.05) related to intestinal function. More research is needed to confirm that gene expression upregulation by PDP in combination with SDP has an impact on intestinal function and to elucidate its underlying mechanisms.

Background: Porcine digestive peptides (PDP) have proven to be a valid substitute for other high-quality dietary protein sources for piglets, like spray-dried plasma (SDP), but knowledge about their influence on intestinal function is still scarce. This study was conducted to investigate the effects of PDP, SDP or a combination of both on growth performance and intestinal function of weaned pigs. Results: A total of 180 piglets (Trial 1) and 198 piglets (Trial 2) were used to evaluate the partial substitution of soybean ingredients with 2% SDP or 2% PDP (Trial 1), and with 3% SDP or the combination of 1% SDP and 2% PDP (SDP-PDP; Trial 2) during the pre-starter period (d0-14). A common commercial diet was offered up to day 35 in Trial 2. The effects on intestinal function were evaluated by quantifyingthe gene expression (56 genes in an Open Array Real-Time PCRPlatform) in jejunum and ileum samples obtained from piglets on d 14 after weaning (Trial 2).Piglets fed SDP, PDP and SDP-PDP had a higher body weight (BW), average daily gain (ADG) and feed efficiency (G:F) than the soybean controlon day 14 (P< 0.05), but no differences were observed among groups at the end of starter phase (Trial 2). Ten genes in jejunum and five in ileum samples were differentially expressed among treatments (P< 0.05). The highest expression was found in the SDP-PDP group. These genes are involved in the barrier function of intestinal cells,the immune response, mucosal nutrient transport, digestion and metabolization of oxidation products. Conclusion: The combination of SDP and PDP upregulated genes related to the intestinal functionwithout affecting growth performance. The underlying mechanisms that produced these effects are still unknown; however, protein hydrolysates might contain bioactive peptides that could be the cause.

It is known that pigs can acquire flavour preferences by brief social interactions with conspecifics that previously consumed a flavoured solid feed. However, there is no information about whether a flavoured solution could support flavour preferences through social transmission. Ninety-six pigs (49 days old) were housed in 12 pens (8 pigs/pen). Four animals per pen were randomly selected to act as observers and four as demonstrators. Demonstrator animals were temporarily moved to an empty pen where a protein solution was offered (porcine digestive peptides (PDPs), 4% weight/volume) with the addition of 0.075% aniseed (six pens) or garlic (six pens) powdered artificial flavours for 30 min. Afterwards, demonstrators were returned to interact with observer animals for 30 min. A choice test (30 min) between aniseed and garlic PDP was performed for each observer group after the interaction. Observers showed a higher intake of solutions previously consumed by their demonstrator conspecifics (648 v. 468 ml; SEM 61.36, P < 0.05). As with flavoured solid feeds, protein solutions containing artificial flavours can create preferences in pigs for those flavours through social transmission from conspecifics.

The analysis of the operational flexibility in power systems allows to identify the operational condition of an electrical network over all possible generating scenarios, its critical contingencies classified by their impact on the system, and other topics like limitations of the generation resources or requirements of load curtailment. A geometrical approach to determine and analyze power systems' secure regions is developed using Computational Geometry concepts, like Convex Hulls and Dirichlet Tessellations. This paper shows how the secure-operating region is calculated, following predefined reliability criteria, and how to quantify the operational flexibility through an index which takes into consideration the relative size of the aforementioned region. In addition, a novel contingency ranking based on the dominance of constraints is presented. This ranking is complemented by the notion of surrounding layers of the secure-operating region. The proposed formulation may be applied efficiently in large power systems.

A total of 552 entire male and female nursery pigs were selected to be used in 2 different experiments that aimed to study if milk ingredients can be replaced by highly preferred protein sources (Exp. 1) and if pre- and postnatal exposure of those protein ingredients through the maternal diet may increase pig performance (Exp. 2). In Exp. 1, 240 pigs were separated after weaning (28 d) into 2 groups depending on the presence of lactose in their diets. Pigs ( =120) fed diets with the precence of lactose (lactose +) were given prestarter (0-14 d) and starter (15-33 d) diets with 142 and 50 g/kg of sweet milk whey, respectively; the lactose-free group ( = 120) was offered an isoenergetic diet with 20 g/kg of porcine-digestible peptides (PDP; Palbio 62SP; Bioiberica S.A., Palafolls, Spain) and wheat replacing sweet milk whey. Choice and 1-feeder tests were performed in another group of animals ( = 72) to evaluate the preference and acceptance for both diets. Pigs preferred ( = 0.039) the lactose+ over the lactose-free diet after a 30-min choice test and consumed more ( = 0.001) lactose+ than lactose-free diet in a 1-feeder test. However, no difference ( > 0.467) in performance was observed between groups for the entire nursery period. In Exp. 2, 120 animals were obtained from sows that, during late gestation (14 d) and lactation (28 d), were fed diets containing 20 g/kg of PDP and another 120 animals were obtained from sows fed an isoenergetic diet without PDP inclusion. Placenta samples were collected at farrowing to assess the volatile compounds present in the placental fluid of sows. After weaning, all pigs received a feed containing 20 g/kg of PDP in the prestarter and starter diets. A principal components analysis of the total volatile compounds showed the exclusive presence of sulfur-containing compounds and a higher presence of terpene compounds in the placental fluid of PDP-supplemented sows. In addition, pigs coming from sows fed diets supplemented with PDP tended to show a higher ADFI ( = 0.07) and ADG ( = 0.06) than did pigs coming from control sows during the 15 to 33 d after-weaning period. These results suggest that dietary incorporation of sweet milk whey may be replaced by a specific protein source without affecting performance of pigs after weaning. However, more experiments are needed to elucidate the mechanism for the sow's diets' influence over pig's performance.

Porcine mucosa hydrolysate sprayed into a soybean meal carrier (PMH) is a co-product of heparin production from clean endothelial digestive tissues. An experiment was conducted to evaluate growth performance and ileal morphology of broilers fed diets with or without PMH inclusion. There were 8 dietary treatments arranged as a 2 × 4 factorial with two levels of PMH (0 vs. 25 g/kg diet) and four levels of lysine (Lys; 11, 12, 13 and 14 g/kg diet). Diets were formulated to have similar apparent metabolizable energy (AMEn) content and within each Lys level, the indispensable amino acid to AMEn ratio was maintained constant. Birds received the experimental diets from d 1 to 21 and then, a common commercial finisher diet without PMH inclusion from d 21 to 32. Each treatment was replicated five times and the experimental unit was the pen with 32 chicks. An interaction between PMH inclusion and Lys content of the diet was detected for body weight gain (BWG) from d 1 to 7; PMH inclusion improved BWG ( P = 0.013) in all cases but the effects were more noticeable in birds fed the low Lys diets ( P P P

A total of 552 entire male and female nursery pigs were selected to be used in 2 different experiments that aimed to study if milk ingredients can be replaced by highly preferred protein sources (Exp. 1) and if pre- and postnatal exposure of those protein ingredients through the maternal diet may increase pig performance (Exp. 2). In Exp. 1, 240 pigs were separated after weaning (28 d) into 2 groups depending on the presence of lactose in their diets. Pigs ( =120) fed diets with the precence of lactose (lactose +) were given prestarter (0-14 d) and starter (15-33 d) diets with 142 and 50 g/kg of sweet milk whey, respectively; the lactose-free group ( = 120) was offered an isoenergetic diet with 20 g/kg of porcine-digestible peptides (PDP; Palbio 62SP; Bioibérica S.A., Palafolls, Spain) and wheat replacing sweet milk whey. Choice and 1-feeder tests were performed in another group of animals ( = 72) to evaluate the preference and acceptance for both diets. Pigs preferred ( = 0.039) the lactose+ over the lactose-free diet after a 30-min choice test and consumed more ( = 0.001) lactose+ than lactose-free diet in a 1-feeder test. However, no difference (0.467) in performance was observed between groups for the entire nursery period. In Exp. 2, 120 animals were obtained from sows that, during late gestation (14 d) and lactation (28 d), were fed diets containing 20 g/kg of PDP and another 120 animals were obtained from sows fed an isoenergetic diet without PDP inclusion. Placenta samples were collected at farrowing to assess the volatile compounds present in the placental fluid of sows. After weaning, all pigs received a feed containing 20 g/kg of PDP in the prestarter and starter diets. A principal components analysis of the total volatile compounds showed the exclusive presence of sulfur-containing compounds and a higher presence of terpene compounds in the placental fluid of PDP-supplemented sows. In addition, pigs coming from sows fed diets supplemented with PDP tended to show a higher ADFI ( = 0.07) and ADG ( = 0.06) than did pigs coming from control sows during the 15 to 33 d after-weaning period. These results suggest that dietary incorporation of sweet milk whey may be replaced by a specific protein source without affecting performance of pigs after weaning. However, more experiments are needed to elucidate the mechanism for the sow's diets' influence over pig's performance.

Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjögren syndrome (pSS). The aim of the present investigation was to establish if serum IgG antibodies (pSS IgG) were able to interact with cholinoreceptors in rat submandibular gland-dependent stimulation of cyclooxygenase 2 (COX-2) mRNA expression and PGE2 production. Our findings indicated that pSS IgG-stimulating M3, M4, and M1 cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE2 production. Inhibitors of phospholipase A2, COX- s, L-type calcium channel currents, and Ca2+-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE2 production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE2 production. Moreover, the amounts of PGE2 in saliva and in sera from persons with pSS were significantly higher than in pre- or post-menopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.

In the weaning period, transition from sow's milk to the post-weaning diet causes the withdrawal of important nutrients as milk nucleotides, which are known to be determinant for the development of the gastrointestinal tract and immune function. The objective of these investigations was to study the effect of including these nucleotides in solid diets for piglets. Nucleotide composition of sow's milk was analyzed using 5 sows at 21 days of lactation. The average free nucleotide concentration was 102.8 ± 9.16 μmol/100 mL. Two experiments were performed to assess the effect of a product based on this composition (Nucleoforce Piglets®) on digestive adaptation and incidence of diarrhoea of nursery piglets. In Exp. 1, three groups of 6 piglets were weaned at 21 days of age and fed with a diet supplemented with 0 (control), 1000 or 2000 ppm of nucleotides, and a fourth group of 6 piglets was maintained in lactation. Seven days after weaning, piglets were euthanized and samples of jejunal mucosa were processed for histological measurements. Villus height decreased from 448 μm in un-weaned pigs to 275 μm in the control group 7 days after weaning. Although there were no differences in feed intake among groups, the reduction in villous height was less pronounced (P

Pigs can learn to prefer a flavor if it has been previously associated to positive consequences. The aim of this experiment was to study flavor preferences conditioned by the postingestive effect of nutrients in pigs. In total, 240 weanling piglets were allocated in 24 pens (10 piglets/pen) and distributed to 2 groups of animals (12 pens per group). Pigs in Group 1 (G1) were trained during 8 d with one flavor [positive conditioned stimulus (CS+)] into a protein solution [4% porcine digestible peptides (PDP)] on odd days and another flavor [negative conditioned stimulus (CS-)] into 100 mM of monosodium glutamate (MSG) solution on even days (5-L bottle for 24 h). In the second group of pigs [Group 2 (G2)], CS+ was mixed into a 4% sucrose solution in odd days and CS- into 1% sucrose + 0.08% saccharine on even days. Therefore, treatments were defined as CS+, the flavor associated with PDP or sucrose, on odd days, which were assumed to have a higher postingestive effect than MSG or saccharine + sucrose, the ingredients associated to CS-. Concentration of ingredients in the solutions were chosen to ensure that hedonic attraction for PDP and MSG solutions and for sucrose and saccharine + sucrose were similar (checked in previous double-choice studies). The amount of solution offered during training period was prepared to be totally consumed each day to equalize flavors intake. Flavors (0.0375% anise or garlic) were counterbalanced across replicates to act as CS+ or CS-. Double-choice test between flavors dissolved in water (CS+ and CS-) were performed by selecting 2 pigs/pen on days 1, 6, and 8 after the training period. Solution intake was measured after 30 min. Piglets showed higher intakes for CS+ than CS- in G2 [212 vs. 76 mL and 168 vs. 86 mL (P < 0.05) and 195 vs. 78 mL (P = 0.15)] on days 1, 6, and 8, respectively. Differences between CS+ and CS- consumption were observed in G1 on day 8 (231 vs. 130 mL; P < 0.05). In conclusion, weanling pigs can acquire flavor preferences through associative learning between a flavor and postingestive effects of some nutrients.

Physiological state or dietary nutrient content can be determinants of the sensory perception with consequences for feed preferences. The aim of the present study was to assess whether the preference for protein or carbohydrate of piglets is affected by dietary energy density. In total, 240 weanling piglets (28 d old; initial BW 7.2 ± 1.1 kg) were allocated to 24 pens (10 pigs/pen) according to BW. Piglets were split up into 2 groups and had ad libitum access to a high energy (HE; 3.90 Mcal DE/kg; crude fat 129 g/kg) or a low energy (LE; 3.35 Mcal DE/kg; crude fat 60 g/kg) diet with similar CP content (190 g/kg). Piglet performance and preference for protein [porcine digestible peptides (PDP; Palbio 62SP, Bioibérica, Palafolls, Spain) 20 g/L] or carbohydrate (sucrose 20 g/L) solutions were measured on days 14 and 21 after weaning using a double-choice test (DCHT). The LE diet promoted a higher (P0.05) ADFI and ADG than the HE diet. Final BW on day 21 was higher (P0.001) for piglets fed the LE diet than piglets fed the HE diet (12.8 vs. 11.5 kg). Preference (P0.05) was not observed for protein or carbohydrate solutions on day 14 or 21 in piglets fed the LE diet. On the other hand, piglets fed the HE diet had higher (75% on day 14 and 65% on day 21; P0.01) preference for the sucrose solution. Dietary energy level and consequent nutrient imbalances, such as dietary protein-to-energy ratio, may affect feed preference for protein or carbohydrate solutions in piglets.

1. The beta3-adrenoceptor agonist ZD 7114, like the non-selective beta-adrenoceptor agonist isoprenaline, but unlike the beta1-adrenoceptor agonist dobutamine and the beta2-adrenoceptor agonist salbutamol, produced an increment on mouse embryonic fibroblast proliferation. The half-maximal stimulation of cell growth occurred at substantially lower concentrations with the beta3-adrenoceptor agonist (EC50: 5.5 x 10(-8) m) than with isoprenaline (EC50: 1.25 x 10(-6) m). 2. The selective beta3-adrenoceptor antagonist SR 5923 OA prevented the beta3-stimulated fibroblast proliferation. Conversely, practolol and butoxamine did not prevent fibroblast growth. 3. Additionally, a decrease of cAMP was obtained in fibroblasts cells upon stimulation with isoprenaline and ZD 7114. 4. The expression of beta-adrenoreceptors on fibroblast cells was also studied by radioligand binding. The Ki values in the presence of beta1- and beta2-adrenoceptor antagonist was two-fold higher than the Ki values for beta3 adrenoceptor antagonist indicating the presence of A3-receptor subtype. 5. Inhibitors of different intracellular coupling pathways including phospholipase C (U 73122), protein kinase C (staurosporine), calcium/calmodulin (trifluoroperazine) and calcium channel (verapamil), prevented the stimulatory actions of the selective beta3-adrenoceptor agonist ZD 7114. 6. The presence of beta3-adrenoceptors on embryonic mouse fibroblast cells may play a role in the modulation of cell growth and biologic activity. The mechanism by which ZD 7114 triggers cell proliferation and function, involves the activation of phospholipase C, PKC, calcium/calmodulin and the influx of calcium.

As from January to August 2013, epidemiological weeks 1-35 (EW), Influenza incidence, case characteristics, types and subtypes of circulating influenza virus in the Nacional Profesor Alejandro Posadas Hospital were studied, and were compared to incidences during 2009-2012. From late May to the end of August 2013 (EW18-35), an increase was observed in the proportion of patients' visits for respiratory disease, influenza-like illness and hospitalizations due to pneumonia; of 207 cases diagnosed with influenza A virus, 153 were infected by H1N1pdm09, 46 by H3, and eight without subtype. The highest proportion of cases was found in children under five years of age, followed by the group 60-64. The chances of having the illness were three times greater among the group 40-64 years old compared to 15-39 or those older than 64. Mortality, which increased with age, was 7.2%, and the odds of death were six times higher among those older than 64. Vaccination rate among the cases was 11.6%. None of the fatal cases had received the vaccine. After the 2009 pandemic, the proportions of annual patients' visits decreased until 2012; in 2013, an increase of 52.0% during the winter period compared to 2012. The viral circulation started earlier in 2013 compared to previous years. FLU-A(H1N1pdm) was the predominant circulating virus in 2009 and 2013, FLU-A(H3) in 2011, FLU-A(H3) and FLU-B in both 2010 and 2012.

Summary In this paper, we report the effect of standard NDGA, as compared to that of an aqueous extract of Larrea divaricata Cav., on BW 5147 lymphoma cell-line proliferation. To determine the mechanism of action, the effects of both on the level of intracellular cAMP, protein kinase C activity and calcium influx were studied. Moreover, the NDGA present in the aqueous extract of the plant was quantified. The aqueous extract and the standard NDGA showed antiproliferative action against these cells. While the antiproliferative activity of the aqueous extract was mediated by an increase in cAMP levels, and inhibition of PKC and calcium influx, the antiproliferative activity of NDGA was related only to the inhibition of PKC. Considering the amount of NDGA detected in the aqueous extract of the plant, at the concentrations analyzed in this case, antiproliferative activity of Larrea divaricata cannot be attributed to this compound, but could have an additive effect on the activity of other compounds.

Pigs can learn to prefer a flavor if it has been previously associated to positive consequences. The aim of this experiment was to study flavor preferences conditioned by the postingestive effect of nutrients in pigs. In total, 240 weanling piglets were allocated in 24 pens (10 piglets/pen) and distributed to 2 groups of animals (12 pens per group). Pigs in Group 1 (G1) were trained during 8 d with one flavor [positive conditioned stimulus (CS+)] into a protein solution [4% porcine digestible peptides (PDP)] on odd days and another flavor [negative conditioned stimulus (CS-)] into 100 mM of monosodium glutamate (MSG) solution on even days (5-L bottle for 24 h). In the second group of pigs [Group 2 (G2)], CS+ was mixed into a 4% sucrose solution in odd days and CS- into 1% sucrose + 0.08% saccharine on even days. Therefore, treatments were defined as CS+, the flavor associated with PDP or sucrose, on odd days, which were assumed to have a higher postingestive effect than MSG or saccharine + sucrose, the ingredients associated to CS-. Concentration of ingredients in the solutions were chosen to ensure that hedonic attraction for PDP and MSG solutions and for sucrose and saccharine + sucrose were similar (checked in previous double-choice studies). The amount of solution offered during training period was prepared to be totally consumed each day to equalize flavors intake. Flavors (0.0375% anise or garlic) were counterbalanced across replicates to act as CS+ or CS-. Double-choice test between flavors dissolved in water (CS+ and CS-) were performed by selecting 2 pigs/pen on days 1, 6, and 8 after the training period. Solution intake was measured after 30 min. Piglets showed higher intakes for CS+ than CS- in G2 [212 vs. 76 mL and 168 vs. 86 mL (P0.05) and 195 vs. 78 mL (P = 0.15)] on days 1, 6, and 8, respectively. Differences between CS+ and CS- consumption were observed in G1 on day 8 (231 vs. 130 mL; P0.05). In conclusion, weanling pigs can acquire flavor preferences through associative learning between a flavor and postingestive effects of some nutrients.

A single population of alpha 2 adrenoceptors was characterized in intact B lymphocytes from patients with chronic lymphocytic leukemia (B-CLL) by binding and saturation studies with 3H labelled yohimbine and by competition studies with alpha adrenergic antagonists. While the affinity of B-CLL alpha 2 adrenoceptors was low (KD: 9.81 nM-20.98 nM), each cell expressed a large number of receptors. No binding of the alpha 1 adrenoceptor antagonist prazosin was observed and the binding properties of beta adrenergic receptors (assayed with 3H-labelled dihydroalprenolol), were similar to those described for normal lymphocytes. Reaction of B-CLL with the beta adrenergic agonist isoproterenol raised the levels of cAMP in 11/13 patients tested, and in 8 of these, incubation with the alpha 2 adrenergic agonist clonidine prevented the effect and reduced the basal cAMP levels. The presence of active alpha 2 adrenoceptors on B-CLL lymphocytes may be involved in the regulation of metabolic pathways that affect cell functions and favor neoplastic growth.

The authors investigated whether circulating autoantibodies against M(3) muscarinic acetylcholine receptors (mAChRs) could be a new marker for diagnosis for primary and secondary Sjögren syndrome (SS) dry eye.Enzyme-linked immunosorbent assay (ELISA) using both rat exorbital lacrimal gland acinar cell membranes and synthetic 25-mer peptide as antigens was used to determine autoantibodies against acinar cells and M(3) mAChRs. Also, nitric oxide synthase (NOS) activity was assessed to determine the biological effect of these autoantibodies in relation to the M(3) mAChR.Sera from dry eye primary SS (pSS) or secondary SS (sSS) patients tested by ELISA recognized membrane lacrimal gland acinar cells antigens and the synthetic 25-mer peptide, corresponding to the second extracellular loop of human M(3) mAChRs. Moreover, the IgG fraction and the corresponding affinity-purified anti-M(3) peptide autoantibodies from the same patients were able to activate NOS coupled to lacrimal gland M(3) mAChRs. As controls, IgG and sera from women without dry eye with or without rheumatoid arthritis and from normal control subjects gave negative results on ELISA and biological assay; thus demonstrating the specificity of the reaction.Autoantibodies against mAChR may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes and could be a new marker to differentiate SS dry eyes from non-SS dry eyes.

Evidence accumulated by our investigations over the years give adequate proof for the existence of circulating antibodies in Chagas disease which bind to beta adrenergic and muscarinic cholinergic receptor of myocardium. The interaction of agonist-like antibodies with neurotransmitter receptors, triggers in the cells intracellular signal transductions that alter the physiological behaviour of the target organs. These events convert the normal cells into pathologically active cells. The interaction of antibodies with heart beta adrenergic and cholinergic receptors triggers physiologic, morphologic, enzymatic and molecular alterations, leading to tissue damage. The analysis of the prevalence and distribution of these antibodies reveals a strong association with cardiac and esophageal autonomic dysfunction in seropositive patients in comparison with those without alteration of the heart and esophagus autonomic disorders: therefore, the presence of these antibodies may partially explain the cardiomyoneurophathy and achalasia of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies behaving like an agonist on neurotransmitter receptors, induceds desensitization and/or down regulation of the receptors. This in turn, could lead to a progressive blockade of neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described during the course of Chagas cardioneuropathy and achalasia. The clinical relevance of these findings is the demonstration, using biomolecules, of a strong association between the existence of circulating autoantibodies against peptides corresponding to the second extracellular loop of the human heart beta, adrenoceptor and M2 cholinoceptor in chagasic patients, and the presence of dysautonomic symptoms, making these autoantibodies a proper early marker of heart and digestive autonomic dysfunction.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that has a large number of immunologic and nonimmunologic functions. We have described that IFN-gamma could activate muscarinic cholinergic receptors (mAchR) of rat intestine, stimulating ileal motility. We also observed that mAchR activation induced inhibition of cAMP levels and stimulation of cGMP formation. The objectives of our work were to clarify the signal transduction pathways involved in regulation of ileal motility through mAchR activation by IFN-gamma. Our results demonstrate that this cytokine produces an ileal cholinergic response through tyrosine kinase activity. The activation of tyrosine kinase mediates ileal contractility, phosphoinositide hydrolysis by phospholipase C, nitric oxide synthase via protein kinase C, and cGMP synthesis. The increment in ileal motility is probably due to hyperproduction of prostaglandin E2 (PGE2) by ileal tissue. This prostanoid is an important mediator because it stimulates ileal motility. We conclude that IFN-gamma not only immunomodulates the gut microenvironment but also exerts a local nonimmunologic regulation on intestinal motility.

Here we demonstrate that T. cruzi antigen molecule SAPA (shed acute phase antigen) with neuraminidase-trans sialidase activity triggers down-regulation of T lymphocyte proliferation by interacting with T lymphocyte muscarinic acetylcholine receptors (mAChR). SAPA attachment to mAChR from Lyt 2.2+ T cells resulted in synthesis of cyclic GMP (cGMP) and secretion of PGE2, an immunoregulator effector substance. These T suppressor cell signals were blunted by atropine and by indomethacin. Cell sorter analysis showed that the interaction of SAPA with purified T cells, affected the ratio of L3T4+/Lyt 2.2+ T cells increasing the percentage of Lyt 2.2+ T cells, effect that was inhibited by the mAChR antagonist, atropine. The interaction between SAPA and mAChR from Lyt 2.2+ T cells may result, therefore, in the down-regulation of the host immune response as consequence of T suppressor/cytotoxic cells activation and PGE2 release as they were observed. These results support the theory of an immunosuppressive state that contribute to the chronic course of Chagas' disease.

The authors demonstrated that immunoglobulin G, present in the sera of patients with primary Sjögren syndrome (pSS), could recognize and activate muscarinic acetylcholine receptors (mAChRs) of rat exorbital acrimal gland.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and radioligand binding and biologic assays were used to demonstrate autoantibodies against mAChRs.These autoantibodies recognized by means of SDS-PAGE and immunoblotting assay a band of approximately 70 kDa expressed on lacrimal gland membranes that comigrated with the peak of labeled mAChRs. Moreover, pSS IgG were able to inhibit, in an irreversible manner, the binding of [3H]quinuclidinyl benzilate to mAChRs of rat exorbital lacrimal glands and to simulate the biologic effect of mAChR agonists, because they trigger the activation of phosphoinositide turnover. Atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide blocked the effect and carbachol mimicked it, confirming that the M3 subtype mAChRs mediated pSS IgG action. As control, IgG from sera of women without pSS gave negative results on immunoblotting, binding, and biologic assays, thus demonstrating the specificity of the reaction.Autoantibodies against mAChRs may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes.

To study the possibility that schistosomiasis might be able to spread into the basins of the Paraná and Uruguay rivers, 1,711 snails were experimentally exposed to infection with Schistosoma mansoni. These snails were laboratory-bred progeny of Biomphalaria tenagophila collected from 15 populations in the geographic area under consideration. Three strains of S. mansoni were used: BH2, adapted to B. glabrata, and SJ and SJ2 adapted to B. tenagophila. None of the 543 snails exposed to the BH2 strain became infected, nor did any of the 668 exposed to SJ. However, of the 500 exposed the SJ2, 4 of the 163 snails (2%) from Ayolas, a locality in the Paraná basin, were susceptible, as were 8 of 45 (18%) from Fuente, Salto, in the Uruguay basin. These findings are similar to those of studies done in other geographic areas, where some populations of B. tenagophila do not become infected with S. mansoni while others are susceptible. The results of this study signal the possibility of the expansion of schistosomiasis into a broad region of South America in which B. tenagophila is found.

An epidemiologic study was conducted in San Cayetano, a village in the province of Corrientes, Argentina, to determine the prevalence of intestinal parasitoses in children. Eighty-eight households were randomly selected. Stool samples were collected from 207 children (72% of the school-age population and 12% of the total village population) over a period of six consecutive days, and were subjected to microscopic examination. Of the samples examined, 170 (83%) contained one or more parasites, of which the most frequently found was Blastocystis hominis (in 43% of the samples). Other parasites and commensals detected included Giardia lamblia (29%), hookworms (27%), Entamoeba coli (27%), Enterobius vermicularis (4%), Strongyloides stercoralis (2%), and Ascaris lumbricoides, Trichuris trichiura, Taenia saginata, Isospora belli, Iodamoeba bütschlii, and Balantidium coli (each 0.5%). The high observed prevalence of intestinal parasitoses indicates active parasite transmission in San Cayetano as a result of poor environmental hygiene-ascribable largely to a lack of public water supply, sewerage, and waste removal services.

We have recently shown that rat interferon-gamma (IFN gamma) can trigger a cholinergic muscarinic response upon interaction with isolated rat atria, decreasing both the contractile tension and cAMP synthesis, and increasing cGMP production. Because the intestine is rich in cholinergic muscarinic receptors, and IFN gamma-producing cells are normal components of the mucosal immune system, we investigated whether IFN gamma could also modulate the muscarinic cholinergic activity of the intestine. Our results indicate that IFN gamma may interact with ileum cholinergic muscarinic receptors by inhibiting binding of the radiolabelled antagonist quinuclidinyl benzylate (3H-QNB), decreasing cAMP formation and increasing cGMP synthesis. These effects are associated with increased mechanical activity of the isolated ileum strips, and can be blunted by pretreatment of the tissue with atropine.

We previously reported that aqueous extract of Larrea divaricata Cav. had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. To determine the probable mechanism of the inhibitory action of the extract upon cell growth, the participation of intracellular signals involved in the inhibition of cell proliferation, namely the activation of adenylate cyclase system was studied. The production of cyclic 3', 5 adenosine monophosphate (cAMP) in presence and absence of extract was analized. The extract increased the cAMP levels, but neither the cAMP production nor the inhibitory effect of the extract on proliferation were blocked by a beta adrenergic receptor antagonist (propranolol) or by histaminergic receptor antagonists (cimetidine and mepyramine). So, we concluded that the antiproliferative activity of the extract of BW 5147 cells would be mediated by an increase in cAMP intracellular levels no related to the activation of the membrane receptors here studied. In parallel, the extract was administered to a pregnant rat with a spontaneous mammarian carcinoma and "in vivo" antitumoral activity was found.

Herein we demonstrate by ELISA and immunoblotting the presence in the sera of chagasic patients of circulating autoantibodies against the third extracellular domain of human muscarinic acetylcholine receptors by using a synthetic peptide corresponding to the sequence 169-192 of the receptor. Immunoaffinity purified antipeptide antibodies displayed cardiac muscarinic activity as decreased contractility and cAMP production and increased cGMP levels. These effects were specifically blocked by the synthetic peptide and by atropine. A strong association between the existence of circulating autoantibodies and the presence of dysautonomia was shown, making these autoantibodies an appropriate marker of heart autonomic dysfunction.

Erythropoietin is considered unique among the hematopoietic growth factor with a specific action on the differentiation and proliferation of erythroid progenitor cells. We have observed a dose-dependent modulatory action of human recombinant erythropoietin (rHuEpo) stimulated the rate of cell growth but at higher ones (3-10 U/ml) inhibited it. The mitogenic action of the hormone is correlated with cardiac membrane Na(+)-K(+)-ATPase activity since concentrations of rHuEpo that increased cell growth stimulated paranitrophenilphosphatase (pNPPase) activity, while those concentrations that inhibit the enzyme markedly bloqued its mitogenic action. Moreover, ouabain (10(-5) M), concentration that inhibits Na(+)-K(+)-ATPase activity, blunted the stimulatory action of rHuEpo on cell proliferation. We also demonstrated that rHuEpo while activated the cardiac membrane Na(+)-K(+)-ATPase was able to alter the contractile action of ouabain on isolated neonatal rat atria. Indeed rHuEpo (1 U/ml) enhanced the non toxic action of the cardiac glycoside attenuating and delaying the onset of the toxic effect of the drug. These results show that rHuEpo has a non hematopoietic cardiac effect, associated with the cardiac Na(+)-K(+)-ATPase activity, that regulates the myocytes growth and the biological action of cardiac glycosides on isolated rat myocardium.

Female Balb/c mice were mated to C3H male mice, to obtain an allopregnant IgG. This allopregnant IgG con activate beta-adrenoceptors of C3H uterus. Here we show that allopregnant IgG interacts with beta-adrenoceptors in uterus of C3H mice and produces a decrease of the spontaneous motility and an increase of the intracellular cAMP concentration. Both effects are blocked by propranolol, a beta-adrenergic antagonist. Allopregnant IgG interferes with the binding of a specific beta adrenergic radioligand 3H-dihydroalprenolol behaving as a non competitive inhibitor. All these data indicate that allopregnant IgG could modulate the activity of uterine beta-adrenoceptors.

Induction of polyphosphoinositide hydrolysis in cardiac tissue by IgG from chagasic mice was assayed. BALB/c mice auricles were labelled with myo-[3H]inositol precursor and inositol phosphate production in the presence or absence of chagasic IgG and the corresponding F(ab')2 was measured. Both chagasic IgG and F(ab')2 but not the normal forms specifically increased phosphoinositide turnover. This increment was blocked by muscarinic cholinergic antagonists and to an even greater extent by the phospholipase C inhibitor NCDC. Moreover, calcium channel blocking agents such as diltiazem, verapamil and D-600 also exerted an inhibitory action. A muscarinic cholinergic agonist, carbachol, and the ionophore A-23187, mimicked the action of the chagasic IgG upon phosphoinositide turnover. It is concluded that murine chagasic IgG and its F(ab')2 fragments result in stimulation of phospholipase C-mediated phosphoinositide hydrolysis through the interaction with muscarinic cholinergic receptors requiring the cytosolic calcium concentration to be raised.

We studied the effect of transformed lymphocytes from patients with chronic lymphocytic leukaemia (CLL) and the Raji cell (Raji) on the response of rat isolated atria to sodium arachidonate (AA). In contrast to normal lymphocytes, CLL cells and Raji cells decrease the contractile tension of rat isolated atria. Addition of exogenous AA (1.98 X 10(-6) M) to Raji, further reduced the isometric developed tension. Time of culture of Raji was important, as the negative inotropic effect was greater at 72 h than at 24 h of culture. Living cells were required and cell-free supernatants were inactive. Preincubation of CLL cells or Raji with cyclooxygenase inhibitors (acetyl salycilic acid, indomethacin) or inhibitors of thromboxane (TX) synthesis (imidazole, L-8027) abolished the negative inotropic response suggesting the contribution of TXs. L-8027 also reduced the growth rate of Raji cells, indicating that TXs may play a role in the regulation of cell division. The production of TXs by CLL and Raji cells from both endogenous and exogenous sources provided additional support to this hypothesis and suggested that activation of this metabolic pathway may be related to cell transformation.

The results of this study show that peripheral blood mononuclear leukocytes of patients with Chagas' disease (Ch-PBMC) respond to challenge with homologous as well as with heterologous heart antigens releasing active soluble factors capable of increasing the conractile tension and frequency of beating rat atria. The reaction was related to T . cruzi infection rather than to the presence of cardiomypathy. Indirect evidence suggests that supernatants of Ch-PBMC activated with heart tissue homogenates involved the generation of arachidonic acid metabolites by the lipoxygenase system of rat atria. Active effector cells were present in Ch-PBMC that had been depleted of T8-lymphocytes by lysis with OKT8 and rabbit complement (C) and not in those depleted of T4-lymphocytes with OKT4 and C. Therefore, the positive inotropic and chronotropic effects of Ch-PBMC were due to the action of cells from the T4 subset.

The aim of this work was to study the effect of lymphocytes from individuals infected with Trypanosoma cruzi (Chagas' patients) on the contractile behaviour of living heart tissue. Chagas' lymphocytes (ChL) reacted with isolated rat atria preparations increasing the isometric development tension (IDT) and frequency of contractions (FC) in a dose-dependent manner. The maximal stimulatory effect was reached after 30-40 min of contract. In contrast, normal lymphocytes (NL) did not alter the basal IDT and FC values. beta-adrenergic antagonists, anti-histamine agents and inhibitors of the synthesis and action of arachidonic acid (AA) products were used to study the mechanisms of the reaction. (-)-propranolol (10(-7)M) and pyrilamine (10(-6)M) had no effect ruling out the participation of beta-adrenergic agonists or histamine. However, indomethacin (10(-6)M) and acetylsalicylic acid (1.8 X 10(-4)M) enhanced the effect of ChL. Inhibitors of the lipoxygenase pathway (5,8,11,14-eicosatetraynoic acid, 10(-7)M; nordihydroguairetic acid, 10(-5)M) and FPL55712, an antagonist of one of its terminal products: the slow reacting substance of anaphilaxis (SRS-A), abolished the reaction. Therefore, a fundamental role for SRS-A in the production of the stimulatory effect is postulated. Lymphocytes of the T cell lineage (E rosette forming cells, ERFC) are the effector cells involved in this reaction, whereas non-rosetting ChL depressed IDT. T ascertain if effector cells could be replaced by soluble factors, ChL were reacted with homogenates of rat atria and the cell free supernatants were added to beating rat atria. Positive ino- and chronotropic effects were obtained, indicating that soluble factors generated during the reaction can substitute for the intact effector cells. On the other hand if the effector cells were purified from Chagas' patients that had been treated 1 month to 6 years before the assay with trypanocidal drugs (3-methyl-4-(5'-nitrofurfurylidene-amino)-tetrahydro-4H-1, 4-tiazine-1, 1-dioxide, nifurtimox or N-benzyl-2-nitro-imidazolacetamide, benznidazole) only depressor effects were found. The depressor inotropic action of lymphocytes from treated patients (tr-ChL) was abolished with indomethacin and acetyl salicylic acid indicating that products of the cyclooxygenase pathway of AA were involved. While this work provides additional evidence for the hypothesis that lymphocytes from T. cruzi infected patients may react with heart tissue and alter its contractile behaviour, the results should not be extrapolated to the in vivo situation.(ABSTRACT TRUNCATED AT 400 WORDS)

Contractility responses of mice atria to alpha-adrenergic agonists (methoxamine and clonidine) were studied. The alpha-adrenergic agonists increased the rate of force development (dF/dt) and decreased contractile frequency. The positive inotropic effect was mediated through cardiac alpha-adrenoceptors, while the negative chronotropic effect involved parasympathetic activation. Blockers of phospholipase C inhibited both the positive inotropic and the negative chronotropic effects of the alpha-adrenergic agonists. Inhibitors of phospholipase A2 and cyclooxygenase activity attenuated the positive inotropic effect of the agonists without modifying the negative chronotropic effect.

The effects of acetylcholine and bethanechol on the basal resting tone of the isolated detrusor muscle were explored. It was observed that the tone was augmented by both agents. On the other hand, in the presence of prostaglandin (PG)-inhibitors the dose-response curve of acetylcholine shifts to the right. PGF 2 alpha (10(-10)M) but not PGE2 (10(-10)M) completely blocked the inhibitory effect of PG-inhibitors upon the inotropic effect of acetylcholine, without modifying the influence of bethanechol. After inhibitors of PG-synthesis, eserine abolished the inhibitory action of acetylcholine but did not change the influence of bethanechol. Our results suggest that endogenous PGs facilitate the action of acetylcholine through an increase in the concentration of the cholinergic neurotransmitter probably via an inhibition of the acetylcholinesterase activity.

Activated lymphocytes may have potent biologic effects outside the frame of the immune system. In these studies we analyzed the interaction of activated normal human lymphocytes and/or soluble products of lymphocyte activation on the contractile activity of isolated rat atria. The results indicate that phytohemagglutinin activated lymphocytes of the CD4 phenotype exert a positive inotropic effect on spontaneously beating atria. This effect is linked to steps of lymphocyte activation that precede cell division. Soluble factors released to the supernatant of stimulated lymphocytes can substitute for the intact cells. Interleukin-2 (IL-2) appears to be an important component of the active supernatants, as their activity can be reduced by monoclonal anti-IL-2 or by preincubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-Tac). Highly purified IL-2 was active at 10 units/ml. In order to induce a positive inotropic effect at lower doses of natural or recombinant IL-2 (2-3 units/ml), synergic factors were required (2 x 10(-6) M arachidonic acid, AA, or Ca ionophore A 23187). Indirect evidence indicates that IL-2 exerts its biologic effect by turning on the phosphoinositide cycle and activating protein kinase C in the heart tissue target. It is postulated that similar mechanisms may be activated in inflammatory myocardiopathies or during the treatment of cancer with massive doses of IL-2.