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To analyze the distribution and factors associated with lack of knowledge about the human papillomavirus (HPV) vaccine among Brazilian adolescents.Cross-sectional study using the 2019 National School Health Survey among 17,805 Brazilian students of public and private schools, aged 13-17 years. The outcome variable was "lack of knowledge about the HPV vaccine" and the explanatory variables were sociodemographic, behaviors, knowledge, and health conditions. Logistic regression model was used to calculate Odds Ratio (OR) and 95% confidence intervals (95%CI). Spatial analysis techniques were used to determine the formation of clusters in the federated units with similar proportions of adolescents who were unaware of the vaccine. The lack of knowledge about the HPV vaccine was reported by 45.54% of Brazilian students. There was a higher chance of lack of knowledge having had sexual intercourse (OR 1.43; 95% CI 1.20-1.70); attending public school (OR 1.72; 95%CI 1.47-2.02) and located in the Northeast Region (OR 1.35; 95%CI 1.08-1.69). The lower chance of lack of knowledge were female gender (OR 0.41; 95% CI 0.35-0.48), higher maternal education (OR 0.62; 95% CI 0.50-0.77) self-rated health as Poor/very poor (OR 0.64; 95% CI 0.49-0.86) and receiving contraceptive counseling (OR 0.77; 95% CI 0.65-0.91). The proportion of lack of knowledge about the HPV vaccine was higher with the formation of High-High spatial clusters in the states of Maranhão, Piauí, and Pernambuco. Sociodemographic, health, and behavioral conditions and knowledge of students, as well as school characteristics, were associated with lack of knowledge about the HPV vaccine. A higher frequency of lack of knowledge about the HPV vaccine among adolescents was found in the states of the Northeastern Region.
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BACKGROUND AND PURPOSE: Inflammatory changes in the fat tissue surrounding the coronary arteries have been associated with coronary artery disease and high-risk vulnerable plaques. Our aim was to investigate possible correlations between the presence and degree of perivascular fat density and a marker of vulnerable carotid plaque, namely contrast plaque enhancement on CTA. MATERIALS AND METHODS: One-hundred patients (76 men, 24 women; mean age, 69 years) who underwent CT angiography for investigation of carotid artery stenosis were retrospectively analyzed. Contrast plaque enhancement and perivascular fat density were measured in 100 carotid arteries, and values were stratified according to symptomatic (ipsilateral-to-cerebrovascular symptoms)/asymptomatic status (carotid artery with the most severe degree of stenosis). Correlation coefficients (Pearson ρ product moment) were calculated between the contrast plaque enhancement and perivascular fat density. The differences among the correlation ρ values were calculated using the Fisher r-to-z transformation. Mann-Whitney analysis was also calculated to test differences between the groups. RESULTS: There was a statistically significant positive correlation between contrast plaque enhancement and perivascular fat density (ρ value = 0.6582, P value = .001). The correlation was stronger for symptomatic rather than asymptomatic patients (ρ value = 0.7052, P value = .001 versus ρ value = 0.4092, P value = .001). CONCLUSIONS: There was a positive association between perivascular fat density and contrast plaque enhancement on CTA. This correlation was stronger for symptomatic rather than asymptomatic patients. Our results suggest that perivascular fat density could be used as an indirect marker of plaque instability.
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Tejido Adiposo/patología , Estenosis Carotídea/patología , Placa Aterosclerótica/patología , Tejido Adiposo/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Angiografía por Tomografía Computarizada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Our aim was to assess the relationship between volume and percentage of intraplaque hemorrhage measured using CT and the occurrence of cerebrovascular events at the time of CT. MATERIALS AND METHODS: One-hundred-twenty-three consecutive subjects (246 carotid arteries) with a mean age of 69 years who underwent CTA were included in this retrospective study. Plaque volume of components and subcomponents (including intraplaque hemorrhage volume) was quantified with dedicated software. RESULTS: Forty-six arteries were excluded because no plaque was identified. In the remaining 200 carotid arteries, a statistically significant difference was found between presentation with cerebrovascular events and lipid volume (P = .002), intraplaque hemorrhage volume (P = .002), percentage of lipid (P = .002), percentage of calcium (P = .001), percentage of intraplaque hemorrhage (P = .001), percentage of lipid-intraplaque hemorrhage (P = .001), and intraplaque hemorrhage/lipid ratio (P = .001). The highest receiver operating characteristic area under the curve was obtained with the intraplaque hemorrhage volume with a value of 0.793 (P = .001), percentage of intraplaque hemorrhage with an area under the curve of 0.812 (P = .001), and the intraplaque hemorrhage/lipid ratio with an area under the curve value of 0.811 (P = .001). CONCLUSIONS: Results of our study suggest that Hounsfield unit values <25 have a statistically significant association with the presence of cerebrovascular events and that the ratio intraplaque hemorrhage/lipid volume represents a strong parameter for the association of cerebrovascular events.
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Estenosis Carotídea/patología , Hemorragia Cerebral/patología , Trastornos Cerebrovasculares/etiología , Placa Aterosclerótica/patología , Anciano , Estenosis Carotídea/complicaciones , Hemorragia Cerebral/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/complicaciones , Curva ROC , Estudios RetrospectivosRESUMEN
The reactions of 1,3,5-triaminobenzene derivatives with 2,3,4-trinitrothiophene and 2-bromo-3,4,5-trinitrothiophene gave new all-conjugated compounds bearing both an electron-withdrawing and an electron-donor moiety on the same unit. The reactions with 2,3,4-trinitrothiophene offered evidence, by NMR spectroscopy at low temperature, of the formation of new labile Wheland-Meisenheimer intermediates whereas at room temperature stable unexpected products derived from the attack of the nucleophile at C-4 with replacement of the nitro group were isolated. Their formation caused, in turn, the obtainment of a salt between 1-nitroso-2,4,6-triaminobenzenes and 2,4-dinitrothiophen-3-ol. The reactions with 2-bromo-3,4,5-trinitrothiophene produced in good yields the SNAr substitution product with the displacement of the bromide. All the new coupling products obtained are of applicative interest, considering the increasing concern for highly conjugated π-systems in solar energy conversion or optoelectronic devices.
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New all-conjugated C-C coupling products bearing both an electron-poor and an electron-rich aromatic moiety have been obtained from the reaction between sym-triaminobenzene derivatives and a series of isomeric chloro-nitrobenzofurazans. The reactions occur under mild reaction conditions, and in some cases a different behaviour depending on the presence, or not, of triethylamine was observed. From 1,3,5-tris(N-morpholinyl)benzene and 5-chloro-4-nitrobenzofurazan in the presence of triethylamine an unexpected product derived from the shift of the nitro group from C-4 to C-5 of the electrophile and bearing the nucleophile at position 4 was obtained. Moreover, from the coupling between 1,3,5-tris(N-pyrrolidinyl)benzene and 4-chloro-7-nitrobenzofurazan a highly stable Wheland intermediate was isolated.
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OBJECTIVE: Formaldehyde is an effective and popular semipermanent hair straightener, but the severe consequences for human health due to its toxicity have prompted the search for safer alternatives. Different carbonyl compounds, including glyoxylic acid, have recently been proposed as promising candidates. Despite the interest in this topic, there is a lack of information about the interactions between hair keratin and straightener agents. This study addresses this issue to gain new insights useful in the development of new products for safe, semipermanent hair deformation. METHODS: The possible reactions occurring between carbonyl groups and nucleophilic sites on amino acid residues belonging to the keratin were investigated using as model compounds some aldehydes and amino acid derivatives. Raman and IR analyses on yak hair subjected to the straightening treatment with glyoxylic acid in different conditions were carried out. Scanning electron microscope (SEM) analyses were carried out on yak and curly human hair after each step of the straightening procedure. RESULTS: The reactions between aldehydes and N-α-acetyl-L-lysine revealed the importance of the carbonyl electrophilicity and temperature to form imines. Raman and IR analyses on yak hair subjected to the straightening treatment evidenced rearrangements in the secondary structure distribution, conformational changes to the disulphide bridges, a decrease of the serine residues and formation of imines. It was also indicated that straightening produced major conformational rearrangements within the hair fibre rather than on the cuticle. CONCLUSION: This investigation revealed the role played by the electrophilicity of the carbonyl on the straightener agent and of the temperature, closely related to the dehydration process. Raman and IR studies indicated the involvement of imine bonds and the occurrence of a sequence of conformational modifications during the straightening procedure. SEM analyses showed the effectiveness of the treatment at the cuticular level.
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Formaldehído , Glioxilatos , Preparaciones para el Cabello , Aldehídos/química , Aminoácidos/química , Humanos , Microscopía Electrónica de Rastreo , Modelos Químicos , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría RamanRESUMEN
Introducción. El asma bronquial es una enfermedad inflamatoria crónica de las vías respiratorias. La reversibilidad de sus síntomas es su característica. La carga epigenética es un factor importante. Las estadísticas de mortalidad son una fuente importante de información para la salud ya que nos permite establecer estrategias terapéuticas preventivas. La Clasificación Internacional de Enfermedades CIE 10 nos provee un sistema alfanumérico vasto y didáctico. Objetivos. (1) Informar las tasas y porcentajes de fallecimientos por enfermedades del aparato respiratorio ocurridas entre los años 2000 a 2007 en la Provincia de Santa Fe y (2) Informar qué porcentaje y tasas de fallecimientos ocupa el asma bronquial dentro de las enfermedades crónicas de las vías respiratorias Inferiores. Material y métodos. El Ministerio de Salud de Santa Fe suministró los datos obtenidos de los certificados de defunción en el período 2000-2007; los informes se hacen en base a las normas de la OMS a través de la CIE 10, agrupados en el cap. 10 J00 a J99. Resultados. Objetivo 1: haciendo el análisis de los grupos J00 a J99 se puede observar que el mayor porcentaje de muerte es debido a neumonías agudas (J10 a J18) con 37%, le siguen J95 a J99 con 27%. Luego J40-J47 con el 22%. Este grupo incluye al asma y estado asmático con 3% del total. Los códigos J80 -84 y J60- 70 siguen con el 7 y 6% respectivamente. Objetivo 2: cuando analizamos en número y porcentaje las causas de muerte en el grupo 5 (J40-47), el grupo J44 (EPOC) tiene 82%, el grupo J45-46 (asma) 11%, el grupo J43 (enfisema) 4%, elgrupo J41-42 (bronquitis) 3% y el grupo J47 (bronquiectasias) menos del 1%. La tasa de mortalidad por asma bronquial en la provincia de Santa Fe años 2000- 2007 da un promedio anual de 24 muertes por millón de habitantes. En el grupo de 5-34 años es de 1,2 por millón de habitantes. La tasa de mortalidad por EPOC en el mismo período da un promedio de 187 por millón de habitantes. Conclusiones. Las tasas de muerte por asma son altas y los porcentajes de otras patologías del aparato respiratorio también son altas. La única fuente de datos son los certificados de defunción y es poco precisa a la hora de realizar estadísticas a pesar de ser coherentes comparando los datos de diferentes regiones del mundo. Para ajustar las estadísticas deberíamos analizar si el enfermo muere por su asma (válida) o muere con su asma (no válida). (AU)
Background. Bronchial asthma is a chronic inflammatory disease of the airways characterized by the reversibility of symptoms. The epigenetic burden is a major factor. Mortality statistics are an important source of health information since they allow us to establish preventive treatment strategies. The International Classification of Diseases, Tenth Revision (ICD-10) provides an extensive and educational alphanumeric system. Aims: (1) To report rates and percentages of respiratory system deaths occurred between years 2000-2007 in the province of Santa Fe; and (2) To report rates and percentages of deaths due to bronchial asthma among "chronic diseases of the lower respiratory system". Material and methods: The Ministry of Health of Santa Fe provided data from death records for the period between 2000 and 2007. Reports are based on WHO norms using the ICD-10 codes J00 to J99 from chapter X. Results: (1) A detailed analysis of codes J00 to J99 showed that the highest percentage of deaths are due to acute pneumonias (J10 to J18), accounting for 37% of deaths, followed by codes J95 to J99 with 27% and codes J40-J47 with 22%. This last group includes asthma and status asthmaticus with 3% of the total. There follow codes J80 -84 and J60-70 with 7% and 6%, respectively. (2) After assessing the number and percentages of causes of death from chronic lower respiratory diseases (J40-47), code J44 (chronic obstructive pulmonary disease) accounts for 82% of deaths, codes J45-46 (asthma-status asthmaticus) for 11%, code J43 (emphysema) for 4%, codes J41-42 (bronchitis) for 3% and code J47 (bronchiectasis) for less than 1%. Over the period 2000-2007, mortality rates from bronchial asthma in the province of Santa Fe yield an annual average of 24 deaths per million inhabitants; being 1.2 deaths per million inhabitants in the 5-34 age-groups. COPD mortality rates during that same period give an average of 187 deaths per million inhabitants. Conclusions. Asthma death rates are high as well as percentages from other respiratory system conditions. The only source of data are death records, which are scarce and imprecise to perform statistical calculations; despite being consistent with data from different regions of the world. To adjust statistics, we should determine if patients die from their asthma (valid) or with their asthma (not valid).(AU)
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Humanos , Niño , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Enfermedades Respiratorias , Asma/mortalidad , Mortalidad , Sistema RespiratorioRESUMEN
BACKGROUND/AIMS: Endoscopic variceal banding ligation (EVL), first described by Stiegmann in 1988, is now an accepted alternative to sclerotherapy (EVS) for esophageal varices with previous bleeding. However, results are conflicting in terms of complications, eradication, recurrence, rebleeding and mortality rate. We aimed to compare EVL with EVS in a prospective randomized trial in patients with previous esophageal bleeding proved by endoscopy. End points were rebleeding rate and death during a short (eradication period) or long-term follow-up (> 1 year). METHODOLOGY: One hundred patients (50 EVL, 50 EVS) were enrolled. Eradication rate, number of treatments needed to achieve eradication, recurrence of varices, rebleeding and complications were recorded and analyzed. RESULTS: No differences were observed between the two groups regarding age, sex and Child class. One patient dropped out in the EVL group and 6 in the EVS group. Eradication was obtained in 44 (88%) with EVL and 41 (82%) with EVS with a mean of 3.41 and 5.29 treatments (p<0.001), respectively. Rebleeding occurred during eradication in 6 patients (12%) in the EVL group and 21 (42%) in the EVS group (p=0.001); after eradication, 7 patients (14%) rebled in the EVL group and 4 (8%) in the EVS group (not significant). Non-variceal bleeding was observed in 5 patients (2 EVL and 3 EVS) during follow-up. Two patients in the EVL group died after variceal rebleeding; 3 died of gastric bleeding; and, 15 from non-hemorrhagic events (8 EVL and 7 EVS). In the EVL group 14 patients had recurrent varices and 7 rebled; in the EVS group 11 recurred, with rebleeding in 5. Major complications were fewer in the EVL group (1 stenosis, 4 chronic ulcers) compared to 18 patients in the EVS group (9 stenosis and 9 chronic ulcers) (p<0.005). CONCLUSIONS: EVL might be preferable to EVS for faster reduction and obliteration of varices, with a lower rate of complications and rebleeding before eradication. No differences were observed in recurrence.
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Várices Esofágicas y Gástricas/terapia , Escleroterapia , Adulto , Anciano , Anciano de 80 o más Años , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/mortalidad , Esofagoscopía , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/terapia , Humanos , Ligadura , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Retratamiento , Tasa de SupervivenciaRESUMEN
We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing human umbilical vein endothelial cells for 24 h to normal (5 mM), high concentration of glucose (30 mM), advanced glycosylation end product-albumin (100 microg/ml), or hyperglycemic (174-316 mg/dl) sera from patients with diabetes and abnormal hemoglobin A1c (8.1+/-1.4%). At the end of incubation endothelial cells were perfused with total leukocyte suspension in a parallel plate flow chamber under laminar flow (1.5 dyn/cm2). Rolling and adherent cells were evaluated by digital image processing. Results showed that 30 mM glucose significantly (P < 0. 01) increased the number of adherent leukocytes to endothelial cells in respect to control (5 mM glucose; 151+/-19 versus 33+/-8 cells/mm2). A similar response was induced by endothelial stimulation with IL-1beta, here used as positive control (195+/-20 cells/mm2). The number of rolling cells on endothelial surface was not affected by high glucose level. Stable adhesion of leukocytes to glucose-treated as well as to IL-1beta-stimulated endothelial cells was preceded by short interaction of leukocytes with the endothelial surface. The distance travelled by leukocytes before arrest on 30 mM glucose, or on IL-1beta-treated endothelial cells, was significantly (P < 0.01) higher than that observed for leukocytes adhering on control endothelium (30 mM glucose: 76.7+/-3.5; IL1beta: 69.7+/-4 versus 5 mM glucose: 21.5+/-5 microm). Functional blocking of E-selectin, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 on endothelial cells with the corresponding mouse mAb significantly inhibited glucose-induced increase in leukocyte adhesion (67+/-16, 83+/-12, 62+/-8 versus 144+/-21 cells/ mm2). Confocal fluorescence microscopy studies showed that 30 mM glucose induced an increase in endothelial surface expression of E-selectin, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1. Electrophoretic mobility shift assay of nuclear extracts of human umbilical vein endothelial cells (HUVEC) exposed for 1 h to 30 mM glucose revealed an intense NF-kB activation. Treatment of HUVEC exposed to high glucose with the NF-kB inhibitors pyrrolidinedithiocarbamate (100 microM) and tosyl-phe-chloromethylketone (25 microM) significantly reduced (P < 0.05) leukocyte adhesion in respect to HUVEC treated with glucose alone. A significant (P < 0.01) inhibitory effect on glucose-induced leukocyte adhesion was observed after blocking protein kinase C activity with staurosporine (5 nM). When HUVEC were treated with specific antisense oligodesoxynucleotides against PKCalpha and PKCepsilon isoforms before the addition of 30 mM glucose, a significant (P < 0.05) reduction in the adhesion was also seen. Advanced glycosylation end product-albumin significantly increased the number of adhering leukocytes in respect to native albumin used as control (110+/-16 versus 66+/-7, P < 0.01). Sera from diabetic patients significantly (P < 0.01) enhanced leukocyte adhesion as compared with controls, despite normal levels of IL-1beta and TNFalpha in these sera. These data indicate that high glucose concentration and hyperglycemia promote leukocyte adhesion to the endothelium through upregulation of cell surface expression of adhesive proteins, possibly depending on NF-kB activation.
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Endotelio Vascular/fisiología , Glucosa/farmacología , Hiperglucemia/metabolismo , Leucocitos/fisiología , FN-kappa B/metabolismo , Adhesión Celular , Moléculas de Adhesión Celular/biosíntesis , Endotelio Vascular/efectos de los fármacos , Productos Finales de Glicación Avanzada/farmacología , Hemorreología , Humanos , Procesamiento de Imagen Asistido por Computador , Microscopía por Video , FN-kappa B/antagonistas & inhibidores , Oligonucleótidos Antisentido/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/genética , Regulación hacia ArribaRESUMEN
The aim of the present study was to assess in the rat the pharmacological, biochemical and molecular (including in situ hybridization) consequences in the striatum of a prolonged (50 days) treatment with dizocilpine maleate (MK-801), an N-methyl-D-aspartate (NMDA) antagonist. We observed a sensitization-like effect characterized by a behavioural hyperresponsiveness to an acute injection of haloperidol (0.25 mg/kg), a dopaminergic antagonist. In rats chronically treated with MK-801, this hyperresponsiveness was associated with an increased D2 receptor (D2R) density in the striatum. At the transcriptional level, the D2R mRNA was also enhanced in the striatum. Quantitative in situ hybridization studies revealed that the number of neurons expressing the D2R mRNA was significantly enhanced in treated rats, whereas the mean amount of message per cell was unchanged. These changes could represent the neurobiological substrate of the observed sensitization. These results suggest that the D2R gene is under glutamate control via NMDA receptor in striatal neurons.
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Dopamina/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Neostriado/fisiología , Animales , Conducta Animal/efectos de los fármacos , Northern Blotting , Maleato de Dizocilpina/farmacología , Dopamina/metabolismo , Hibridación in Situ , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Enfermedad de Parkinson Secundaria/fisiopatología , ARN Mensajero/biosíntesis , Ratas , Receptores de Dopamina D2/biosíntesis , Receptores de Dopamina D2/efectos de los fármacosRESUMEN
We investigated the effect of cyclosporine (CyA) on leukocyte adhesion to endothelium under flow conditions. Confluent human umbilical vein endothelial cells (HUVECs) were incubated for 24 hours with CyA (1, 5, and 10 micromol/L) and then exposed to a total human leukocyte suspension in a parallel plate flow chamber under laminar flow (1.5 dynes/cm2. Human umbilical vein endothelial cells stimulated with interleukin-1beta (20 U/mL) were used as a positive control. Adherent cells were measured by digital image analysis. Results showed that CyA dose-dependently increased the number of leukocytes adhering to HUVECs compared with control cells. Leukocyte adhesion markedly increased on HUVECs incubated with interleukin-lbeta, one of the most potent inducers of endothelial cell adhesiveness. Exposure of endothelial cells to CyA did not affect the number of rolling leukocytes, which was similar to control values. To examine the role of adhesion molecules in CyA-induced leukocyte adhesion, HUVECs were incubated with monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin before adhesion assay. Functional blocking of ICAM-1, VCAM-1, and E-selectin on endothelial cells significantly inhibited CyA (10 micromol/L)-induced leukocyte adhesion. Confocal fluorescence microscopy studies showed that CyA induced an increase in the endothelial surface expression of ICAM-1, VCAM-1, and E-selectin. Pretreatment of leukocytes with the platelet activating factor receptor antagonist L659,989 significantly reduced the number of leukocytes adhering to CyA-treated HUVECs. We suggest that CyA enhances leukocyte adhesion to endothelium by upregulating adhesive proteins on endothelial surface membrane. Blocking leukocyte receptor for platelet-activating factor partially prevents adhesion, suggesting a role for endothelial cell-associated platelet-activating factor in the interaction between leukocytes and CyA-treated endothelium.
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Ciclosporina/farmacología , Selectina E/fisiología , Endotelio Vascular/fisiología , Inmunosupresores/farmacología , Molécula 1 de Adhesión Intercelular/fisiología , Leucocitos/fisiología , Factor de Activación Plaquetaria/fisiología , Receptores de Superficie Celular , Receptores Acoplados a Proteínas G , Molécula 1 de Adhesión Celular Vascular/fisiología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Furanos/farmacología , Humanos , Técnicas In Vitro , Interleucina-1/farmacología , Leucocitos/efectos de los fármacos , Microscopía Confocal , Glicoproteínas de Membrana Plaquetaria/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Hemolytic uremic syndrome (HUS), which is the most common cause of acute renal failure in infants and small children, is caused by verotoxin (VT)-producing Escherichia coli infection. Endothelial injury determines microvascular thrombosis and evidence is available from recent studies that suggests that leukocyte activation participates in endothelial damage. We studied here the effect of VT-1 on leukocyte adhesion to vascular endothelium under physiologic flow conditions. Human umbilical vein endothelial cells (HUVECs) were incubated for 24 hours with VT-1 (0.1, 1, and 10 pmol/L) and then exposed to a total leukocyte suspension in a parallel plate flow chamber under laminar flow conditions (1.5 dynes/cm2). Adherent cells were counted by digital image processing. Results showed that VT-1 dose-dependently increased the number of adhering leukocytes to HUVECs as compared with unstimulated cells. The adhesive response elicited by VT-1 was comparable to that of interleukin-1 beta (IL-1 beta), one of the most potent inducers of endothelial cell adhesiveness. Exposure of HUVECs to VT-1 did not affect the number of rolling leukocytes, which was similar to that of control values. To examine the role of adhesion molecules in VT-1-induced leukocyte adhesion, HUVECs were incubated with mouse monoclonal antibodies against E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) before adhesion assay. Functional blocking of E-selectin, ICAM-1, and VCAM-1 on endothelial cells significantly inhibited VT-1-induced increase in leukocyte adhesion. In some experiments, before VT-1 incubation, HUVECs were pretreated for 24 hours with tumor necrosis factor alpha (TNF alpha; 100 U/mL), which is known to increase VT receptor expression on HUVECs. The number of adhering leukocytes on HUVECs exposed to TNF alpha and VT-1 significantly increased as compared with HUVECs incubated with VT-1 and TNF alpha alone. These results suggest that VT-1 modulates leukocyte-endothelium interaction, thus increasing leukocyte adhesion and upregulating adhesive proteins on endothelial surface membrane.
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Toxinas Bacterianas/farmacología , Endotelio Vascular/citología , Hemorreología , Leucocitos/efectos de los fármacos , Animales , Anticuerpos Monoclonales/inmunología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Quimiotaxis de Leucocito/efectos de los fármacos , Niño , Selectina E/biosíntesis , Selectina E/inmunología , Síndrome Hemolítico-Urémico/fisiopatología , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-1/farmacología , Riñón/irrigación sanguínea , Leucocitos/citología , Ratones , Microcirculación , Circulación Renal , Toxina Shiga I , Estimulación Química , Factor de Necrosis Tumoral alfa/farmacología , Venas Umbilicales , Regulación hacia Arriba/efectos de los fármacos , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Molécula 1 de Adhesión Celular Vascular/inmunologíaRESUMEN
Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic clones encoding the human mu- and kappa-opioid receptor genes. Their organization appears similar to that of the human delta receptor gene, with exon-intron boundaries located after putative transmembrane domains 1 and 4. The kappa gene was mapped at position q11-12 in human chromosome 8. A full-length cDNA encoding the human kappa-opioid receptor has been isolated. The cloned receptor expressed in COS cells presents a typical kappa 1 pharmacological profile and is negatively coupled to adenylate cyclase. The expression of kappa-opioid receptor mRNA in human brain, as estimated by reverse transcription-polymerase chain reaction, is consistent with the involvement of kappa-opioid receptors in pain perception, neuroendocrine physiology, affective behavior, and cognition. In situ hybridization studies performed on human fetal spinal cord demonstrate the presence of the transcript specifically in lamina II of the dorsal horn. Some divergences in structural, pharmacological, and anatomical properties are noted between the cloned human and rodent receptors.
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Sistema Nervioso Central/química , Cromosomas Humanos Par 8/genética , Receptores Opioides kappa/genética , Receptores Opioides mu/genética , Adenilil Ciclasas , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Sistema Nervioso Central/fisiología , Mapeo Cromosómico , Clonación Molecular , ADN Complementario/genética , Exones/genética , Biblioteca Genómica , Humanos , Hibridación in Situ , Ligandos , Persona de Mediana Edad , Datos de Secuencia Molecular , ARN Mensajero/aislamiento & purificación , Receptores Opioides kappa/aislamiento & purificación , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/aislamiento & purificación , Receptores Opioides mu/metabolismo , Proteínas Recombinantes/metabolismo , Homología de Secuencia de Aminoácido , Transducción de Señal , Distribución TisularRESUMEN
We investigated the effect of hemodynamic shear forces on the expression of adhesive molecules, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC) exposed to laminar (8 dynes/cm2) or turbulent shear stress (8.6 dynes/cm2 average), or to a static condition. Laminar flow induced a significant time-dependent increase in the surface expression of ICAM-1, as documented by flow cytometry studies. Endothelial cell surface expression of ICAM-1 in supernatants of HUVEC exposed to laminar flow was not modified, excluding the possibility that HUVEC exposed to laminar flow synthetize factors that upregulate ICAM-1. The effect of laminar flow was specific for ICAM-1, while E-selectin expression was not modulated by the flow condition. Turbulent flow did not affect surface expression of either E-selectin or ICAM-1. To evaluate the functional significance of the laminar-flow-induced increase in ICAM-1 expression, we studied the dynamic interaction of total leukocyte suspension with HUVEC exposed to laminar flow (8 dynes/cm2 for 6 hours) in a parallel-plate flow chamber or to static condition. Leukocyte adhesion to HUVEC pre-exposed to flow was significantly enhanced, compared with HUVEC maintained in static condition (233 +/- 67 v 43 +/- 16 leukocytes/mm2, respectively), and comparable with that of interleukin-1 beta treated HUVEC. Mouse monoclonal antibody anti-ICAM-1 completely blocked flow-induced upregulation of leukocyte adhesion. Interleukin-1 beta, which upregulated E-selectin expression, caused leukocyte rolling on HUVEC that was significantly lower on flow-conditioned HUVEC and almost absent on untreated static endothelial cells. Thus, laminar flow directly and selectively upregulates ICAM-1 expression on the surface of endothelial cells and promotes leukocyte adhesion. These data are relevant to the current understanding of basic mechanisms that govern local inflammatory reactions and tissue injury.
Asunto(s)
Moléculas de Adhesión Celular/biosíntesis , Endotelio Vascular/metabolismo , Regulación de la Expresión Génica , Molécula 1 de Adhesión Intercelular/biosíntesis , Proteínas de la Membrana/biosíntesis , Estrés Mecánico , Anticuerpos Monoclonales/farmacología , Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular/genética , Células Cultivadas , Selectina E , Endotelio Vascular/citología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Recién Nacido , Molécula 1 de Adhesión Intercelular/genética , Interleucina-1/farmacología , Leucocitos/citología , Proteínas de la Membrana/genética , Reología , Venas UmbilicalesRESUMEN
N-methyl-D-aspartate antagonists have been proposed as potential therapeutic agents in different neurological diseases, including Parkinson's disease. The effects of gene expression of a chronic treatment with the non-competitive N-methyl-D-aspartate antagonist, dizocilpine maleate (0.8 mg/kg day, per os for 50 days) were analysed in rat striata. Using quantitative in situ hybridization, we measured the messenger RNA expression of the genes encoding D1, D2 dopamine receptors, N-methyl-D-aspartate receptor 1 subunit of N-methyl-D-aspartate receptor, preproenkephalin A and substance P. Chronic treatment with dizocilpine maleate induced a moderate but significant increase in messenger RNA of the N-methyl-D-aspartate receptor 1 subunit in the striatum and the adjacent cortex, suggesting an action of dizocilpine maleate in these two regions. This treatment did not induce any change in D1 receptor, preproenkephalin A or substance P messenger RNA content in the striatum, whereas D2 receptor messenger RNA was increased in the striatum of treated rats. Microscopic analysis revealed that it was the number of medium-sized neurons expressing D2 receptor messenger RNA that was significantly enhanced, while the mean amount of message per cell remained unchanged. These results demonstrate that glutamate via N-methyl-D-aspartate receptors, regulates the D2 receptor gene in striatal neurons. A chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene, suggesting a recruiting phenomenon.
Asunto(s)
Maleato de Dizocilpina/farmacología , Neostriado/citología , Neuronas/metabolismo , Receptores de Dopamina D2/biosíntesis , Animales , Sondas de ADN , Encefalinas/biosíntesis , Hibridación in Situ , Masculino , Neostriado/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/ultraestructura , Núcleo Accumbens/metabolismo , Precursores de Proteínas/biosíntesis , ARN Mensajero/biosíntesis , Ratas , Receptores de Dopamina D1/biosíntesis , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/biosíntesis , Sustancia P/biosíntesisRESUMEN
We have used the mouse delta-opioid receptor (mDOR) cDNA to isolate the mDOR gene and its human homologue. In both species the coding region is interrupted by two introns with conserved exon-intron boundaries located after transmembrane domains 1 and 4. Using the polymerase chain reaction and primers based on the sequence of the cloned human delta-opioid receptor (hDOR) gene, we have obtained a full length cDNA encoding the hDOR from SH-SY5Y neuroblastoma cells. The cDNA sequence is 100% identical to the cloned human genomic sequence and 94% identical to the mouse sequence at the protein level. When expressed in COS cells, hDOR displays nanomolar affinities for delta-selective ligands, whereas the affinities for mu- and kappa-selective ligands are in the micromolar range. The delta agonists [D-Ala2, D-Leu5]enkephalin, cyclic [D-penicillamine2,D-penicillamine5]enkephalin, and BW373U86 efficiently decrease forskolin-induced cAMP levels in hDOR-expressing COS cells, indicating functional coupling of the receptor. The distribution of hDOR mRNA in human brain was investigated using delta-selective reverse transcription-polymerase chain reaction amplification, followed by Southern hybridization with a delta-specific probe. The transcript is found in cortical areas, including olfactory bulb, hippocampus, and amygdala, as well as in basal ganglia and hypothalamus. No expression is detected in internal globus pallidus, thalamus, any investigated brainstem structure, or pituitary gland. Taken together, our results indicate similar structural, pharmacological, functional, and anatomical properties for the hDOR and the mDOR and therefore support the use of rodent models for the study of these receptors in opioid function.
Asunto(s)
Encéfalo/metabolismo , Receptores Opioides delta/genética , Anciano , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario , Humanos , Ratones , Persona de Mediana Edad , Datos de Secuencia Molecular , Unión Proteica , Receptores Opioides delta/metabolismo , Células Tumorales CultivadasRESUMEN
The present paper deals with relationships between neural systems which control motor behaviour (pyramidal and extrapyramidal) and sleep-wakefulness states (in particular the reticular formation). We examined successively their anatomical and neurochemical substrates, electrophysiological and functional motor alterations depending on ascending and descending influences from brain stem during the sleep-wakefulness cycle. These data suggest that sleep-wake states result from the modulation of excitability in neuronal pools and that each state results from the co-ordinated working of several functionally different neuronal pools. Thus, each state could be understood as a sum of behavioural events depending on a neural network. We hypothesized that abnormal motor events occurring specifically during a sleep state could result from motor structures abnormally recruited in neural networks specifically involved in this sleep state.
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Actividad Motora/fisiología , Red Nerviosa/fisiología , Sueño/fisiología , Vigilia/fisiología , Animales , Nivel de Alerta/fisiología , Humanos , Formación Reticular/fisiologíaRESUMEN
The incidence of local recurrence of colo-rectal carcinoma is about 15-50%. The parietal recurrence is localized next parietal incision and its incidence is rare (0.2-2%). The treatment of this lesion is based on palliative radiotherapy and chemotherapy; the surgical treatment is based on parietal resection. The Authors describe a case of parietal recurrence after colo-rectal adenocarcinoma and conclude that the prognosis of this lesions is infaust.
Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Colorrectales/cirugía , Recurrencia Local de Neoplasia , Adenocarcinoma/mortalidad , Anciano , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Recurrencia Local de Neoplasia/mortalidad , Cuidados Paliativos , PronósticoRESUMEN
The role of some so-called primary and secondary (or oligo-elements) elements in the physiopathology of the cardiocirculatory system has been well known from a number of years and they have been regularly included in the treatment protocols. Some, including K, Ca, Mg and Zn, are extremely well known and widely used in clinical practice. Recently, however, a growing number of studies have focused on the biological importance of other oligo-elements in the pathogenetic mechanisms of atherogenesis and its clinical manifestations. This study aimed to verify the exact role of free cobalt in the physiopathology of the chronic obstructive arterial diseases (COAD). A total of 80 patients affected by 2nd stage COAD were examined and the levels of some oligo-elements, including Co, were assayed. Constantly low levels were found (85% of cases) in relation to other oligo-elements studied (Cu, Zn, Mg, Ca). This findings is particularly interesting since it confirms the biochemical hypothesis of atherosclerosis according to which parietal damage plays a central role in the pathogenetic mechanism. Some enzymatic deficiencies, which lead to changes in membrane stability at the level of the endothelial cells, are closely related to the presence of tissutal and humoral peroxidation products. These peroxides (lipid peroxides), which are formed following the interaction of fatty acids with oxygen free radicals, have been identified by a number of studies as being responsible for endothelial damage. Several authors have shown that lipid peroxidation is involved in the atherogenic process through several mechanisms entailing monocytic activity and reduced prostacyclin (PG2) synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)