RESUMEN
The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3µg/site) or histamine (1µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis increased both Tyrode and C48/80-induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S-releasing donors significantly attenuate C48/80-induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine-mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.
Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Inflamación/tratamiento farmacológico , Mastocitos/efectos de los fármacos , Sustancias Protectoras/farmacología , Prurito/tratamiento farmacológico , Piel/efectos de los fármacos , Animales , Gliburida/farmacología , Histamina/metabolismo , Inflamación/metabolismo , Canales KATP/metabolismo , Masculino , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Morfolinas/farmacología , Compuestos Organotiofosforados/farmacología , Prurito/metabolismo , Piel/metabolismoRESUMEN
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30µg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20µg) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines.
Asunto(s)
Sulfuro de Hidrógeno/farmacología , Oligopéptidos/farmacología , Prurito/tratamiento farmacológico , Receptor PAR-2/metabolismo , Animales , Modelos Animales de Enfermedad , Gliburida/farmacocinética , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos/farmacología , Isotiocianatos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Morfolinas/farmacología , Nitroprusiato/farmacología , Compuestos Organotiofosforados/farmacología , Prurito/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismoRESUMEN
This study examined the relationship between the domains of environmental factors, family illegal drug use, parental child-rearing practices, maternal and adolescent personality attributes, and adolescent illegal drug use. A nonclinical sample of 2,837 Colombian youths and their mothers were interviewed about intrapersonal, interpersonal, and environmental factors in their lives. Results indicated that certain environmental factors (e.g., violence, drug availability, and machismo), family drug use, a distant parent-child relationship, and unconventional behavior are risk factors for adolescent illegal drug use. As hypothesized, results showed that the adverse effects of family illegal drug use on adolescent drug use can be buffered by protective parental child-rearing practices and environmental factors, leading to less adolescent illegal drug use. Prevention and treatment efforts should incorporate protective environmental, familial, and intrapersonal components in order to reduce adolescent illegal drug use.
Asunto(s)
Conducta del Adolescente/psicología , Relaciones Familiares , Personalidad , Medio Social , Trastornos Relacionados con Sustancias/psicología , Adolescente , Niño , Femenino , Humanos , Masculino , Factores de Riesgo , América del Sur , ViolenciaRESUMEN
OBJECTIVES: The purpose of this study was to assess the relation of early adolescent marijuana use to late adolescent problem behaviors, drug-related attitudes, drug problems, and sibling and peer problem behavior. METHODS: African American (n = 627) and Puerto Rican (n = 555) youths completed questionnaires in their classrooms initially and were individually interviewed 5 years later. Logistic regression analysis estimated increases in the risk of behaviors or attitudes in late adolescence associated with more frequent marijuana use in early adolescence. RESULTS: Early adolescent marijuana use increased the risk in late adolescence of not graduating from high school; delinquency; having multiple sexual partners; not always using condoms; perceiving drugs as not harmful; having problems with cigarettes, alcohol, and marijuana; and having more friends who exhibit deviant behavior. These relations were maintained with controls for age, sex, ethnicity, and, when available, earlier psychosocial measures. CONCLUSIONS: Early adolescent marijuana use is related to later adolescent problems that limit the acquisition of skills necessary for employment and heighten the risks of contracting HIV and abusing legal and illegal substances. Hence, assessments of and treatments for adolescent marijuana use need to be incorporated in clinical practice.
Asunto(s)
Negro o Afroamericano/psicología , Hispánicos o Latinos/psicología , Abuso de Marihuana/prevención & control , Áreas de Pobreza , Adolescente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Femenino , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Abuso de Marihuana/epidemiología , Ciudad de Nueva York/epidemiología , Oportunidad Relativa , Grupo Paritario , Puerto Rico/etnología , Factores de Riesgo , Trastorno de la Conducta Social/psicologíaRESUMEN
OBJECTIVES: To identify general and differentiating risk and protective factors from domains of culture and ecology, peer, family, and personality, related to adolescent delinquency and marijuana use, and to study the protective role of the parent-child mutual attachment in offsetting cultural and ecological risk factors, leading to less delinquency and marijuana use. DESIGN: Cross-sectional analyses of interview data collected in Colombia. PARTICIPANTS: A total of 2837 Colombian adolescents, 12 to 17 years of age. SETTING: Adolescents were interviewed in their homes. MAIN MEASURES: Independent variables included measures from 4 domains: culture and ecology, peer, family, and personality. The dependent variables were delinquency and marijuana use. RESULTS: Several risk factors, such as tolerance of deviance and sensation seeking, were similarly related to both delinquency and marijuana use, suggesting that a common cause underlies the propensity to engage in different deviant behaviors. Some risk factors were more involved in delinquency and other risk factors were more highly related to the adolescent's marijuana use. Finally, when violence is endemic and illegal drugs are readily available, a close parent-child bond was capable of mitigating these risk factors, leading to less marijuana use and delinquency. CONCLUSIONS: The findings have implications for public health policy related to interventions in countries in which violence and drug use are prevalent. The results point to interventional procedures aimed at adolescents vulnerable to marijuana use and delinquency as well as efforts aimed at specific vulnerabilities in these areas. For example, reducing the risk factors and enhancing the protective factors for marijuana use and delinquency may result in less adolescent marijuana use and delinquency.
Asunto(s)
Delincuencia Juvenil/prevención & control , Abuso de Marihuana/prevención & control , Responsabilidad Parental , Adolescente , Adulto , Niño , Colombia , Estudios Transversales , Femenino , Humanos , Masculino , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
To evaluate the efficacy of ganciclovir, foscarnet, or the combination of both for the treatment of cytomegalovirus polyradiculomyelopathy (CMV-PRAM), we reviewed the records of seven patients with AIDS, diagnosed with CMV-PRAM. Muscle strength was graded according to the Medical Research Council (MRC) scale. Response to treatment was also classified according to MRC scale, based on the degree of improvement in muscle strength. Six of 7 patients had a good response to treatment, reaching the MRC scale of 4, or improving at least 3 degrees in the same scale. CMV-PRAM may be treated with ganciclovir alone or in combination with foscarnet.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Foscarnet/uso terapéutico , Ganciclovir/uso terapéutico , Polirradiculopatía/tratamiento farmacológico , Polirradiculopatía/virología , Enfermedades de la Médula Espinal/tratamiento farmacológico , Enfermedades de la Médula Espinal/virología , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Quimioterapia Combinada , Electromiografía , Femenino , Humanos , Masculino , Tono Muscular/efectos de los fármacos , Resultado del Tratamiento , Retención Urinaria/tratamiento farmacológico , Retención Urinaria/virologíaRESUMEN
OBJECTIVE: To examine the linkages, cultural/ecological factors, and major psychosocial risk factors as they relate to drug use in a sample from Colombia, South America. METHOD: The participants were 1.687 adolescents living in mixed urban-rural communities in Colombia, South America. An individual interview was administered to youths in their homes by Colombian interviewers. The scales used were based on item intercorrelations grouped into the following risk categories: (1) adolescent personality, (2) family traits, (3) peer factors, and (4) cultural/ecological variables. RESULTS: Pearson correlations were computed for each variable and the frequency of marijuana use. Results show that each of the domains was related to adolescent marijuana use, with some notable gender differences. As regards the interrelation of domains, a mediational model was operative. CONCLUSIONS: Findings support a family interactional theory. The domains of family, personality, and peer factors had a direct effect on the adolescents' marijuana use. Implications for prevention are also addressed.
Asunto(s)
Fumar Marihuana/psicología , Personalidad , Ajuste Social , Adolescente , Niño , Colombia , Características Culturales , Familia , Femenino , Humanos , Masculino , Grupo Paritario , Factores de Riesgo , Factores SexualesRESUMEN
Correlational and net regression techniques were used to examine the commonalities and differences in risks for later drug use and delinquency among African American and Puerto Rican adolescents. Eight-eight percent of the risks were significantly related to both problem behaviors. Within the personality, family, peer, ecology, and acculturation domains, many risks independently contributed to the prediction of each problem. Only three risks had a significantly stronger relationship to one of the problem behaviors than to the other. Finding so many common predictors supports a general dimension of problem behavior and highlights the psychosocial risks for drug use and delinquency. The commonalities suggest that interventions targeting these adolescent risks might reduce both problem behaviors.
Asunto(s)
Negro o Afroamericano/psicología , Hispánicos o Latinos/psicología , Delincuencia Juvenil/etnología , Trastornos Relacionados con Sustancias/etnología , Aculturación , Adolescente , Adulto , Familia/psicología , Femenino , Humanos , Masculino , Ciudad de Nueva York/epidemiología , Puerto Rico/etnología , Análisis de Regresión , Factores de Riesgo , Medio SocialRESUMEN
OBJECTIVE: To examine the interrelationship of acculturation, family, personality, ecology, and peer domains measured in adolescence as they impact drug use 5 years later and to assess the role of family variables as buffers against personality risks. METHOD: Youths completed questionnaires in classrooms at T1 and were individually interviewed at T2 (mean age = 20 years). Data were analyzed separately for African-Americans and Puerto Ricans using correlations, hierarchical multiple regressions, and two-way interactions. RESULTS: Most results were similar for both ethnic groups. Eighty percent of the T1 variables significantly related to T2 stage of drug use. A mediational model of the path to drug use was supported. Acculturative influences were associated with family relations, which in turn were related to personality attributes. A reciprocal relationship emerged between the personality and peer domains in their impact on drug use. Family variables primarily enhanced the effect of protective personality traits on drug use. CONCLUSIONS: Stability of drug use alone cannot explain the relationship between the earlier domains and later drug use. Specific adolescent risks have long-lasting effects. The personality domain has a direct effect on later drug use despite a benign picture in the acculturation, family, and peer domains.
Asunto(s)
Conducta del Adolescente , Negro o Afroamericano/estadística & datos numéricos , Salud de la Familia/etnología , Hispánicos o Latinos/estadística & datos numéricos , Trastornos Relacionados con Sustancias/etnología , Aculturación , Adolescente , Adulto , Negro o Afroamericano/psicología , Estudios Transversales , Análisis Factorial , Femenino , Hispánicos o Latinos/psicología , Humanos , Estudios Longitudinales , Masculino , Ciudad de Nueva York/epidemiología , Relaciones Padres-Hijo , Grupo Paritario , Desarrollo de la Personalidad , Puerto Rico/etnología , Análisis de Regresión , Factores de Riesgo , Conformidad Social , Salud UrbanaRESUMEN
The shared and unshared psychosocial risk factors related to stage of drug use and delinquency were examined. The sample consisted of 655 African American and 600 Puerto Rican male and female adolescents. Net regression analysis was used to analyze the data. The results showed that adolescent stage of drug use and delinquency reflect shared and unshared risk factors. The magnitude of the risk factors for adolescent delinquency was greater than for stage of drug use. The findings support a socialization hypothesis (from parent, to personality, to behavior), and the data were congruent with a dispositional model (from child, to parent or peer, to behavior).
Asunto(s)
Negro o Afroamericano/psicología , Hispánicos o Latinos/psicología , Delincuencia Juvenil/psicología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Adolescente , Estudios Transversales , Salud de la Familia , Femenino , Humanos , Delincuencia Juvenil/estadística & datos numéricos , Masculino , Ciudad de Nueva York/epidemiología , Grupo Paritario , Personalidad , Puerto Rico/etnología , Análisis de Regresión , Factores de Riesgo , Muestreo , SocializaciónRESUMEN
Using a family interactional theoretical framework giving primacy to the mutual attachment between parent and child, we examined the interrelationship of acculturation, ecological factors, family, personality, peers, and drug context domains with drug use in an inner city sample. We also assessed the extent to which family protective factors mitigated against risks for drug use from most of the other domains. The sample consisted of 695 African-American and 637 Puerto Rican 7th-10th graders who answered the questionnaire while listening to it on personal tape players in their classrooms. The results of hierarchical regression analyses sufficiently supported the hypothesized sequence of interrelationships in both ethnic groups to substantiate our developmental model of drug use. We also found protective buffers common to both ethnic groups and buffers specific to each group. The implications of the results for targets and timing of intervention in the path to drug use are discussed.
Asunto(s)
Negro o Afroamericano/psicología , Hispánicos o Latinos/psicología , Trastornos Relacionados con Sustancias/psicología , Adolescente , Comparación Transcultural , Familia , Humanos , Relaciones Interpersonales , Masculino , Relaciones Padres-Hijo , Personalidad , Puerto Rico/etnología , Factores de Riesgo , Trastornos Relacionados con Sustancias/etnología , Estados Unidos/etnologíaRESUMEN
This study examines the interactive effects of background factors and personality/attitudinal and perceived environmental dimensions on adolescent drug behavior. Data were collected during home interviews using a structured interview schedule. The sample consisted of 403 British West Indian black, American black, and white adolescents, ranging in age from 13 to 17. Results suggested that two processes, nonconformity to conventional middle class values at both the personality/attitudinal and institutional level, and modeling of familial and peer drug use account in large part for adolescent drug behavior. The majority of correlates of adolescent drug behavior were similar in different sex, age, and ethnic groups.