Foreign body ingestion and associated factors in pediatric patients at a tertiary care center.

INTRODUCTION AND AIMS: Foreign body (FB) ingestion is a common problem in children under 5 years of age and is one of the main indications for endoscopy. The aim of the present study was to describe the clinical, radiographic, and endoscopic characteristics of patients with FB ingestion, as well as the factors associated with the anatomic location and the type of object ingested. MATERIALS AND METHODS: An analytic cross-sectional study was conducted on all patients with FB ingestion seen at the gastroenterology service from January 2013 to December 2018. The data were analyzed using the SPSS program, obtaining frequencies, percentages, medians, and interquartile ranges. Associations were assessed through the chi-square test. RESULTS: Eighty-five patients (52 males and 33 females) were included, with a median age of 4 years. The most common symptom was vomiting (29.4%). Two radiographic projections were carried out in 72.9% of the cases and the stomach was the site where the FB was most frequently visualized (32.9%). The objects most commonly ingested were coins (36%), with esophageal location (p<0.05), as well as objects with a diameter larger than 2cm (p<0.05). An endoscopic procedure was performed on 76 patients (89.4%) for FB extraction, with findings of erythema (28.9%), erosion (48.6%), ulcer (10.5%) and perforation (1.3%). CONCLUSIONS: Numerous factors should be taken into account in the approach to FB ingestion in pediatric patients, including type and size of the FB, time interval from ingestion to hospital arrival, and patient clinical status and age.

Esophagogastric junction outflow obstruction in the differential diagnosis of post-fundoplication dysphagia in children.

INTRODUCTION AND AIMS: Post-fundoplication dysphagia is resolved with no therapeutic intervention in the majority of cases but it can persist in 5.3% of children that undergo the procedure. Among the differential diagnoses, esophagogastric junction outflow obstruction (EGJOO) is a disorder that should be suspected if there is a persistence of dysphagia. The aim of our study was to describe the clinical characteristics, treatment, and follow-up in a case series of patients diagnosed with post-fundoplication EGJOO. MATERIALS AND METHODS: The clinical records of patients diagnosed with EGJOO at a tertiary care hospital within the time frame of September 2015 to September 2019 were reviewed, with respect to manometry, etiology, treatment, and clinical course of the disease. RESULTS: Of the 213 high-resolution esophageal manometries performed, 4 patients met the criteria for post-fundoplication EGJOO. The primary symptom was dysphagia, presenting 15 days after the procedure. Esophageal dilations were carried out on all the patients but with no improvement. Symptoms related to the condition resolved spontaneously in three of the four patients. CONCLUSION: The management of children with post-fundoplication EGJOO continues to be a challenge. Even though more than half of the cases resolve with no intervention, optimum management of the motility disorder is still limited, given the scant experience with the condition in the pediatric population.

Foreign body ingestion and associated factors in pediatric patients at a tertiary care center. / Ingesta de cuerpo extraño en pacientes pediátricos en un hospital de tercer nivel y factores asociados.

INTRODUCTION AND AIMS: Foreign body (FB) ingestion is a common problem in children under 5 years of age and is one of the main indications for endoscopy. The aim of the present study was to describe the clinical, radiographic, and endoscopic characteristics of patients with FB ingestion, as well as the factors associated with the anatomic location and the type of object ingested. MATERIALS AND METHODS: An analytic cross-sectional study was conducted on all patients with FB ingestion seen at the gastroenterology service from January 2013 to December 2018. The data were analyzed using the SPSS program, obtaining frequencies, percentages, medians, and interquartile ranges. Associations were assessed through the chi-square test. RESULTS: Eighty-five patients (52 males and 33 females) were included, with a median age of 4 years. The most common symptom was vomiting (29.4%). Two radiographic projections were carried out in 72.9% of the cases and the stomach was the site where the FB was most frequently visualized (32.9%). The objects most commonly ingested were coins (36%), with esophageal location (p <0.05), as well as objects with a diameter larger than 2cm (p <0.05). An endoscopic procedure was performed on 76 patients (89.4%) for FB extraction, with findings of erythema (28.9%), erosion (48.6%), ulcer (10.5%) and perforation (1.3%). CONCLUSIONS: Numerous factors should be taken into account in the approach to FB ingestion in pediatric patients, including type and size of the FB, time interval from ingestion to hospital arrival, and patient clinical status and age.

Zinc requirements of broiler breeder hens.

One hundred and twenty Cobb 500 hens, 20 wk of age, were randomly allocated into individual cages with the objective of estimating their Zn requirements. The study was composed of 3 phases: adaptation to cages (basal diet), depletion (deficient diet containing 18.7 ± 0.47 ppm Zn) for 7 wk, and experimental phases. Hens were fed diets with graded increments of Zn sulfate heptahydrate (ZnSO4·7H2O), totaling 18.7 ± 0.47, 50.3 ± 10.6, 77.3.0 ± 11.0, 110.2 ± 12.8, 140 ± 12.2, and 170.6 ± 13.2 ppm analyzed Zn in feeds for 12 wk (experimental phase). Requirements of Zn were done using quadratic polynomial (QP), broken line quadratic (BLQ), and exponential asymptotic (EA) models. In general, the non-linear statistical models were the ones that best fit the results in this study. Requirements obtained for hen day egg production and settable egg production were 83.3, 78.6 ppm and 61.4, 65.4 ppm for period of 33 to 36 wk, and 63.3, 53.1 and 60.4, 46.1 ppm for period of 37 to 40 wk, and 62.8, 52.8, and 67.7, 62.1 ppm for period of 41 to 44 wk, respectively, using BLQ and EA models. Total eggs and total settable eggs produced per hen had Zn requirements estimated as 75.7, 64.7 ppm, and 56.5, 41.5 ppm, respectively, for BLQ and EA models, whereas for alkaline phosphatase and eggshell percentage were 161.8, 124.9 ppm and 126.1, 122.4 ppm, using QP and BLQ models. Maximum responses for Zn in yolk for periods of 37 to 40 and 41 to 44 wk were 71.0, 78.1 and 64.5, 59.6 ppm, respectively, using BLQ and EA models. Breaking strength had Zn requirements estimated at 68.0 and 96.7 ppm, whereas eggshell palisade layer and eggshell thickness were maximized with 67.9, 67.9 ppm, and 67.7, 64.4 ppm, respectively, for BLQ and EA models. The average of all Zn requirement estimates obtained by EA and BLQ models in the present study was 72.28 ppm or 11.1 mg/hen/d.

Morfogênese de pastagens de milheto e capim sudão submetidas ao pastejo contínuo / Morphogenesis of millet and sudangrass pastures subjected to continuous grazing

Objetivou-se comparar os parâmetros morfogênicos de pastagens de milheto e capim sudão na Depressão Central do Rio Grande do Sul, manejadas com pastejo contínuo, subdivididos em dois períodos de avaliação. Os tratamentos consistiram em: Milheto = pastagem de milheto (Pennisetum americanum (L.) Leeke) e Sudão = pastagem de capim sudão (Sorghum bicolor cv. sudanense); ambos tratamentos submetidos ao pastejo contínuo com vacas de descarte. O delineamento experimental foi o inteiramente casualizado com 2 tratamentos e 2 períodos. A altura de dossel (32,69 vs 20,29 cm), taxa de aparecimento foliar (0,147 vs 0,080), número total de folhas por perfilho (4,74 vs 3,06), número de folhas vivas (4,26 vs 2,55), número de folhas jovens (1,92 vs 1,47) e número de folhas adultas (2,34 vs 1,08) foram superiores aos perfilhos de pastagens de milheto, enquanto a taxa de senescência foi superior em perfilhos de capim sudão (0,511cm) do que nos perfilhos de milheto (0,495cm). O número total de folhas (4,28 vs 3,53) e número de folhas mortas (0,58 vs 0,38) foram maiores no ciclo inicial de pastejo. Pastagens de milheto apresentam maior potencial vegetativo, ao pastejo, em comparação a pastagens de capim sudão.

The aim of this study was to compare morphogenetic parameters of sudangrass and millet pastures in the Central Depression of Rio Grande do Sul, managed by continuous grazing. The pastures were subdivided into two periods of evaluation. The treatments consisted of pearl millet (Pennisetum americanum (L.) Leeke) and sudangrass (Sorghum bicolor cv. Sudanense), both submitted to continuous grazing by culling cows. The experimental design was completely randomized with two treatments and two periods. The canopy height (32.69 vs 20.29 cm), leaf appearance rate (0.147 vs 0.080), total number of leaves per tiller (4.74 vs 3,06), number of green leaves (4.26 vs 2.55), number of young leaves (1.92 vs 1.47) and number of mature leaves (2.34 vs 1.08) were higher in millet tillers, while the rate of senescence was higher in sudangrass tillers (0.511 cm) compared to millet tillers (0.495 cm). The total number of leaves (4.28 vs 3.53) and the number of dead leaves (0.58 vs 0.38) were higher during the initial grazing cycle. Millet pastures have a greater vegetative growth potential during grazing than sudangrass pastures.

Morfogênese de pastagens de milheto e capim sudão submetidas ao pastejo contínuo / Morphogenesis of millet and sudangrass pastures subjected to continuous grazing

Objetivou-se comparar os parâmetros morfogênicos de pastagens de milheto e capim sudão na Depressão Central do Rio Grande do Sul, manejadas com pastejo contínuo, subdivididos em dois períodos de avaliação. Os tratamentos consistiram em: Milheto = pastagem de milheto (Pennisetum americanum (L.) Leeke) e Sudão = pastagem de capim sudão (Sorghum bicolor cv. sudanense); ambos tratamentos submetidos ao pastejo contínuo com vacas de descarte. O delineamento experimental foi o inteiramente casualizado com 2 tratamentos e 2 períodos. A altura de dossel (32,69 vs 20,29 cm), taxa de aparecimento foliar (0,147 vs 0,080), número total de folhas por perfilho (4,74 vs 3,06), número de folhas vivas (4,26 vs 2,55), número de folhas jovens (1,92 vs 1,47) e número de folhas adultas (2,34 vs 1,08) foram superiores aos perfilhos de pastagens de milheto, enquanto a taxa de senescência foi superior em perfilhos de capim sudão (0,511cm) do que nos perfilhos de milheto (0,495cm). O número total de folhas (4,28 vs 3,53) e número de folhas mortas (0,58 vs 0,38) foram maiores no ciclo inicial de pastejo. Pastagens de milheto apresentam maior potencial vegetativo, ao pastejo, em comparação a pastagens de capim sudão.(AU)

The aim of this study was to compare morphogenetic parameters of sudangrass and millet pastures in the Central Depression of Rio Grande do Sul, managed by continuous grazing. The pastures were subdivided into two periods of evaluation. The treatments consisted of pearl millet (Pennisetum americanum (L.) Leeke) and sudangrass (Sorghum bicolor cv. Sudanense), both submitted to continuous grazing by culling cows. The experimental design was completely randomized with two treatments and two periods. The canopy height (32.69 vs 20.29 cm), leaf appearance rate (0.147 vs 0.080), total number of leaves per tiller (4.74 vs 3,06), number of green leaves (4.26 vs 2.55), number of young leaves (1.92 vs 1.47) and number of mature leaves (2.34 vs 1.08) were higher in millet tillers, while the rate of senescence was higher in sudangrass tillers (0.511 cm) compared to millet tillers (0.495 cm). The total number of leaves (4.28 vs 3.53) and the number of dead leaves (0.58 vs 0.38) were higher during the initial grazing cycle. Millet pastures have a greater vegetative growth potential during grazing than sudangrass pastures.(AU)

Topography and architecture of visual and somatosensory areas of the agouti.

We analyzed the organization of the somatosensory and visual cortices of the agouti, a diurnal rodent with a relatively big brain, using a combination of multiunit microelectrode recordings and histological techniques including myelin and cytochrome oxidase staining. We found multiple representations of the sensory periphery in the parietal, temporal, and occipital lobes. While the agouti's primary (V1) and secondary visual areas seemed to lack any obvious modular arrangement, such as blobs or stripes, which are found in some primates and carnivores, the primary somatosensory area (S1) was internally subdivided in discrete regions, isomorphically associated with peripheral structures. Our results confirm and extend previous reports on this species, and provide additional data to understand how variations in lifestyle can influence brain organization in rodents.

[Variability in walk test conditions in pulmonary rehabilitation programs in Latin America and on the Iberian peninsula]. / Variabilidad en las condiciones de la prueba de la marcha realizada en el contexto de programas de rehabilitación pulmonar en América Latina y en la Península Ibérica.

OBJECTIVE: 1) To determine the frequency of use of the 6-minute walk test in pulmonary rehabilitation programs in Latin America and on the Iberian Peninsula; 2) to identify how the test is performed and possible variations from center to center. MATERIALS AND METHODS: A questionnaire was sent to 55 pulmonary rehabilitation centers in Latin America, Portugal, and Spain. RESULTS: Forty-nine (89.1%) centers answered the questionnaire. Forty-seven (95.9%) perform a walk test lasting 6 minutes; 22 (46.8%) take the longest distance of 2 tests as the real one; and 35 (74.5%) carry out the test in a corridor. The course distance ranged from 17 to 90 meters, but in 21 (44.7%) centers, the corridor was between 17 and 30 meters long. In 29 (61.7%) centers, the patients are routinely informed about the time that had elapsed during the test. Verbal encouragement is used in 44 (93.6%) centers. Thirty-eight (80.8%) use supplemental oxygen when a patient needs it. An increase in absolute values in the distance covered is used as a parameter indicating improvement at 21 (46.7%) sites while at 15 (33.3%) other centers the percentage increase is taken as a measure of improvement. CONCLUSIONS: The 6-minute walk test is widely used for the evaluation of the exercise capacity at the pulmonary rehabilitation centers of Latin America and the Iberian Peninsula. However, there is great variability in the way the test is performed.

Avaliação das equações de referência para predição da distancia percorrida no teste de caminhada de seis minutos em idosos saudaveis brasileiros / Evaluation of the reference equations for predicting walking distances during six-minute walk tests among healthy elderly brazilian subjects

O objetivo deste estudo foi compara as distancias percorridas por idosos no teste de caminhada de seis minutos (TC6) com as distencias previstas pelas equacoesde Enrigh & Sherril, de Troosters et al. e de Enrigh et al. Metodo: 38 idosos saudaveis com idade entre 64 e 82 anos realizaram o TC6 duas vezes. A pressao arterial, as frequencias cardiaca e respiratoria e a saturacao de oxigenio foram mrnsuradas antes e ao final do teste. A analise estatistica empregou o coeficiente de correlacao de Pearson, sendo considerado significativo p<0,05. Resultados: os homens percorreram uma distancia de 410,5 metro e as mulheres, de 371,0 metros. As distancias previstas pelas equacoes de Enrigh & Sherril e Troosters et al. correlacionaram-se com as distancias caminhadas pelas mulheres (r=0,7), nao apresentando correlacao estatisticamente significativa com as distancias percorridas pelos homens. As distancias previstas pela equacao de Enrigh et al. correlacionaram-se com as distancias percorridas por homens (r=0,6) e mulheres (r=0,7). Conclusoes: os resultados demonstram que houve grande variacao entre as distancias percorridas por idosos brasileiros e as previstas pelas equacoes, sendo necessaria a realizacao de estudos adicionais para confirmar a aplicabilidade dessas equacoes para a populacao idosa brasileira

Neurophysiology of the parieto-frontal system during target interception.

We studied the functional properties of neurons of two elements of the parieto-frontal system: area 7a of the PPC and the motor cortex (M1), during an interception task of stimuli moving in real (RM) and apparent motion (AM). The stimulus moved along a circular path with one of 5 speeds, and was intercepted at 6 o'clock by exerting a force pulse on a joystick. A smooth stimulus motion was produced in RM, whereas in AM 5 stimuli were flashed successively at the vertices of a pentagon. The results showed, that a group of neurons in both areas above responded not only during the interception but also during a NOGO task in which the same stimuli were presented in the absence of a motor response. Most of these neurons were tuned to the stimulus angular position. In addition, we found that the time-varying neuronal activity in both areas was related to various aspects of stimulus motion and hand force, with stimulus-related activity prevailing in area 7a and hand-related activity prevailing in M1. Interestingly, the neural activity was selectively associated with the stimulus angle during RM, whereas it was tightly correlated to the time-to-contact during AM. Thus, the results suggest that area 7a was processing high level features of the circularly moving stimuli and was involved in the production of an early command signal for stimulus interception, whereas M1 was still processing some aspect of the visual stimulus that were used to trigger the interception movement using a predictive mechanism.

Therapeutic implications of microglia activation by lipopolysaccharide and reactive oxygen species generation in septic shock and central nervous system pathologies: a review.

The pathophysiology of organ system failure in sepsis, in particular the effects of septic shock on the central nervous system, are still incompletely understood. Lipopolysaccharide (LPS) from Gram-negative bacteria affects the permeability of the blood-brain barrier and causes the activation of brain microglia. A growing body of research supports involvement of activated brain microglia in brain pathologies caused by infectious diseases, trauma, tumors, ischemia, Alzheimer's disease, Parkinson's disease, Down's syndrome, multiple sclerosis and AIDS. Those seminal studies that have contributed to the characterization of the in vivo and in vitro effects of LPS on microglia function, mediator generation and receptor expression are presented within a historical perspective. In particular, all those in vitro studies on O2-, H2O2 and NO. generation by either unprimed or primed microglia have been extensively reviewed. The apparent controversial effect of LPS on microglia O2- is discussed. Because treatment modalities for septic shock have not significantly affected the current high mortality, alternative strategies with antioxidants are currently being investigated. Reduction of microglia O2- generation is proposed as a possible complementary strategy to antioxidative therapy for septic shock and CNS pathologies that involve activated microglia.

Risk of exposure to Chagas' disease among seroreactive Brazilian blood donors.

BACKGROUND: Screening of blood donors for Chagas' disease by using currently available serologic tests is complicated by the lack of adequate sensitivity, discordant results between tests, and the absence of a gold standard. STUDY DESIGN AND METHODS: The study was designed to evaluate the serologic tests by using epidemiologic data relating to the risk of exposure to Trypanosoma cruzi in the urban centers of Brazil. The serologic results obtained from screening 411,617 voluntary blood donations in São Paulo during 1993 and 1994 were reviewed, as well as follow-up results on 1,267 donors who initially were repeatably reactive in at least one of three screening tests. Epidemiologic data were obtained from 321 individuals who on follow-up remained reactive in at least one test and who returned for medical counseling. Controls included 119 screen-negative blood donors and 45 blood donors who were repeatably reactive in at least one screening test but were negative on follow-up. RESULTS: Of the individuals who reacted in three screening tests, 94.6 percent remained reactive on follow-up. Of the individuals who were repeatably reactive in only one screening test, 70.8 percent were negative in all three tests on follow-up. Most individuals who reacted in two or three tests on follow-up had epidemiologic evidence of a risk of exposure to Chagas' disease. A significant proportion (29.1%) of those who were reactive in only one test on follow-up had epidemiologic evidence of exposure to the Chagas' disease vector as compared to 14.6 percent of controls (p = 0.007). This suggests that some of these individuals truly were infected. CONCLUSION: No single test for Chagas' disease is sufficiently sensitive to prevent transfusion transmission of the disease in the urban centers of Brazil.

Distribution of HIV-1 subtypes seen in an AIDS clinic in Sao Paulo City, Brazil.

OBJECTIVE: To determine the distribution of HIV-1 subtypes in Sao Paulo, Brazil. METHODS: Samples were obtained from 80 consecutive HIV-1-infected individuals attending the Immunodeficiency Clinic at the University of Sao Paulo in 1993. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll-Hypaque gradient and a portion was used for routine CD4 counts; the remainder were frozen. PBMC were proteinase-K-digested and DNA-purified by organic extraction. Samples were amplified for the env region of HIV, and envelope sequence subtypes determined by heteroduplex mobility analysis using prototypic subtypes as references. A subset of these were also sequenced through the C2-V3 region of env. RESULTS: A total 69 of 80 samples yielded env polymerase chain reaction product enabling subtype determination; samples that did not amplify were those with low DNA yields. Among 12 injecting drug users (IDU) or sexual partners of IDU, four were typed as clade F and eight as clade B. Forty-three homosexual men or female sexual partners of bisexual men were typed as clade B. The 14 additional cases without known risk factors were typed as clade B. CONCLUSION: These data suggest that subtype F is related to injecting drug use in Brazil.

PIP: Serum samples from 80 consecutive HIV-1-infected individuals presenting to the Immunodeficiency Clinic at the University of Sao Paulo in 1993 were analyzed to determine the distribution of HIV-1 subtypes in the city. Peripheral blood mononuclear cells (PBMC) were separated using Ficoll-Hypaque gradient, a portion was used for routine CD4 counts, and the rest were frozen. PBMC were proteinase-K-digested and DNA-purified by organic extraction. The samples were amplified for the env region of HIV, and envelope sequence subtypes determined by heteroduplex mobility analysis using prototypic subtypes as references. A subset was also sequenced through the C2-V3 region of env. 69 samples yielded env polymerase chain reaction product enabling subtype determination. The samples which did not amplify had low DNA yields. Among 12 IV-drug users or their sex partners, four were typed as clade F and eight as clade B. 43 homosexual men or female sex partners of bisexual men were typed as clade B. The 14 additional cases with no known risk factor were typed as clade B.

Identification of human immunodeficiency virus type 1 envelope genes recombinant between subtypes B and F in two epidemiologically linked individuals from Brazil.

Sequence analysis of a human immunodeficiency virus type 1 env gene PCR amplified from a Brazilian woman's peripheral blood mononuclear cell DNA (sample RJIO1) showed that it was likely to have been derived from a double recombination event between human immunodeficiency virus type 1 subtypes B and F. The major portion of the gp120 coding sequence belonged to the B lineage, but a segment of the C2 to V3 region (approximately 135 nucleotides) clearly associated with sequences of the F lineage. The subtype F-like segment had 15 noncontiguous signature nucleotides in common with Brazilian subtype F sequences that were not found, or were rare, in subtype B sequences. In contrast, this same segment had only 3 signature nucleotides shared with subtype B sequences and not present in the Brazilian subtype F sequences. Phylogenetic analysis, amino acid signature pattern analysis, and the pattern of synonymous mutations all supported the hypothesis of a recombinational origin of the RJIO1 sequence. Related recombinant genes were also detected in peripheral blood mononuclear cell DNA obtained from the woman's recent sexual partner, indicating that the recombination event probably occurred at some previous time in the chain of virus transmission. Divergent viral sequences in the V3 region were found in the male sexual partner, while a relatively homogeneous viral population was detected in the woman, consistent with her recent infection.

Antitumor and cytotoxic screen of 5,6,7-trisubstituted flavones from Gomphrena martiana.

An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity.

[Manoalide: a new phospholipase A2 inhibitor of marine origin with potential immunoregulatory effect]. / Manoalide: un nuevo inhibidor de fosfolipasa A2 de origen marino con una potencial acción inmunorregulatoria.

Manoalide, a non-steroidal sesterterpenoid isolated from a marine sponge, is a potent analgesic and antiinflammatory compound. Manoalide inhibits phospholipase A2 from extracellular sources (snake venoms, bee, etc.), the release of arachidonic acid from rabbit polymorphonuclear leukocytes as well as calcium mobilization. This suggests that the anti-inflamatory effect might be caused by the regulation of eicosanoid biosynthesis. The macrophage plays a major role in the immune response and the inflammatory process, it has the capacity to synthesize and secrete arachidonic acid oxygenation products derived from both cyclooxygenase and lipoxygenase catalyzed pathways, and has been used extensively to study the effect of inhibitors of phospholipases, cyclooxygenase and lipoxygenase enzymes. Our results demonstrate that Manoalide modified the release of arachidonic acid and its further metabolism into prostaglandins and leukotrienes in mouse cultured peritoneal macrophages stimulated by phorbol myristate acetate, calcium ionophore A23187 and zymosan. Since eicosanoids have been shown to cause pain, we studied the possibility that the analgesic effect of Manoalide might be correlated with a decrease of eicosanoid release in vivo. The fact that Manoalide reduced both zymosan-induced peritoneal writhing in the mouse and the synthesis of both 6-keto-prostaglandin F1 alfa and leukotriene C4 suggests that the analgesic effect of Manoalide is at least in part linked to the inhibition of eicosanoid production in vivo. Since it has been shown that eicosanoids have immunoregulatory functions, a future possibility is that a phospholipase A2 inhibitor such as Manoalide may prove useful to investigate the biological role of eicosanoid metabolites on the immune function.

Manoalide: un nuevo inhibidor de fosfolipasa A2 de origen marino con una potencial accion inmunorregulatoria / Monoalide: a new phospholipase A2 inhibitor of marine origin with a potential immunoregulatory effect

Manoalide, un sesterterpenoide no esteroidal aislado de una esponja marina, es un potente analgésico y antiinflamatorio. Manoalide inactiva la enzima fosfolipasa A2 de origen extracelular (veneno de erpiente, abeja, etc.), la liberación del ácido araquidónico de leucocitos polimorfonucleares, como así también bloquea la mobilización del calcio. Estos antecedentes sugierieron la posibilidad de que el efecto antiinflamatorio de Manoalide podría deberse, en parte, a la regulación de la biosíntesis de los eicosanoides. El macrófago participa de la respuesta inmune y del proceso inflamatorio, puede secretar productos oxigenados del ácido araquidónico y ha sido muy utilizado como modelo para estudiar inhibidores de fosfolipasasas, ciclooxigenasas y lipooxigenasas. Nuestros resultados demuestran que Manoalidade modifica la liberación de ácido arquidónico y su posterior metabolismo a prostaglandinas y leucotrienos en el macrófago peritoneal murino estimulado por miristado de forbol, ionóforo de calcio A 23187 y zimosán. Debido al hecho de que se ha demostrado la asociación de los eicosanoides al proceso del dolor se estudió liberación de eicosanoides in vivo, Manoalide inhibió parcialmente el dolor asociado a la inoculación intraperitoneal de zimosán en el ratón, como así también la liberación de 6-keto prostaglandina F1 alfa y leucotrieno C4 en el líquido peritoneal, sugiriendo que el efecto analgésico de Manoalide estaría relacionado en parte a la inhibición de la liberación de los...

Manoalide: un nuevo inhibidor de fosfolipasa A2 de origen marino con una potencial acción inmunorregulatoria. / [Manoalide: a new phospholipase A2 inhibitor of marine origin with potential immunoregulatory effect]

Manoalide, a non-steroidal sesterterpenoid isolated from a marine sponge, is a potent analgesic and antiinflammatory compound. Manoalide inhibits phospholipase A2 from extracellular sources (snake venoms, bee, etc.), the release of arachidonic acid from rabbit polymorphonuclear leukocytes as well as calcium mobilization. This suggests that the anti-inflamatory effect might be caused by the regulation of eicosanoid biosynthesis. The macrophage plays a major role in the immune response and the inflammatory process, it has the capacity to synthesize and secrete arachidonic acid oxygenation products derived from both cyclooxygenase and lipoxygenase catalyzed pathways, and has been used extensively to study the effect of inhibitors of phospholipases, cyclooxygenase and lipoxygenase enzymes. Our results demonstrate that Manoalide modified the release of arachidonic acid and its further metabolism into prostaglandins and leukotrienes in mouse cultured peritoneal macrophages stimulated by phorbol myristate acetate, calcium ionophore A23187 and zymosan. Since eicosanoids have been shown to cause pain, we studied the possibility that the analgesic effect of Manoalide might be correlated with a decrease of eicosanoid release in vivo. The fact that Manoalide reduced both zymosan-induced peritoneal writhing in the mouse and the synthesis of both 6-keto-prostaglandin F1 alfa and leukotriene C4 suggests that the analgesic effect of Manoalide is at least in part linked to the inhibition of eicosanoid production in vivo. Since it has been shown that eicosanoids have immunoregulatory functions, a future possibility is that a phospholipase A2 inhibitor such as Manoalide may prove useful to investigate the biological role of eicosanoid metabolites on the immune function.

Manoalide: un nuevo inhibidor de fosfolipasa A2 de origen marino con una potencial accion inmunorregulatoria / Monoalide: a new phospholipase A2 inhibitor of marine origin with a potential immunoregulatory effect

Manoalide, un sesterterpenoide no esteroidal aislado de una esponja marina, es un potente analgésico y antiinflamatorio. Manoalide inactiva la enzima fosfolipasa A2 de origen extracelular (veneno de erpiente, abeja, etc.), la liberación del ácido araquidónico de leucocitos polimorfonucleares, como así también bloquea la mobilización del calcio. Estos antecedentes sugierieron la posibilidad de que el efecto antiinflamatorio de Manoalide podría deberse, en parte, a la regulación de la biosíntesis de los eicosanoides. El macrófago participa de la respuesta inmune y del proceso inflamatorio, puede secretar productos oxigenados del ácido araquidónico y ha sido muy utilizado como modelo para estudiar inhibidores de fosfolipasasas, ciclooxigenasas y lipooxigenasas. Nuestros resultados demuestran que Manoalidade modifica la liberación de ácido arquidónico y su posterior metabolismo a prostaglandinas y leucotrienos en el macrófago peritoneal murino estimulado por miristado de forbol, ionóforo de calcio A 23187 y zimosán. Debido al hecho de que se ha demostrado la asociación de los eicosanoides al proceso del dolor se estudió liberación de eicosanoides in vivo, Manoalide inhibió parcialmente el dolor asociado a la inoculación intraperitoneal de zimosán en el ratón, como así también la liberación de 6-keto prostaglandina F1 alfa y leucotrieno C4 en el líquido peritoneal, sugiriendo que el efecto analgésico de Manoalide estaría relacionado en parte a la inhibición de la liberación de los... (AU)