RESUMEN
BACKGROUND: A lack of conceptual modeling of how the components of opioid maintenance treatment (OMT) for opioid dependence (OD) work causes it to occasionally be labeled the "black-box" of treatment. This study had a two-fold objective: First, to analyze which factors related to OMT for OD contribute to the abstinence of problematic use of non-prescribed opioids and sustain recovery, from the patients' perspective; second, to understand which changes OMT produced in the individuals' lives might significantly contribute to relapse prevention. METHODS: We used qualitative methods of design, inquiry, and analysis from a convenience sample of 19 individuals in a Swedish treatment setting. RESULTS: All the participants reported previous cycles of problematic use of non-prescribed opioids and other non-prescribed psychoactive substances, treatment, abstinence, recovery, and relapse before starting the current OMT program. During the pre-treatment stage, specific events, internal processes, and social environments enhanced motivation toward abstinence and seeking treatment. During the treatment stage, participants perceived the quality of the human relationships established with primary social groups as important as medication and the individual plan of care in sustaining recovery. From the participants' perspective, OMT was a turning point in their life course, allowing them a sense of self-fulfillment and the reconstruction of personal and social identity. However, they still struggled with the stigmatization produced by a society that values abstinence-oriented over medication-assisted treatments. CONCLUSION: OMT is not an isolated event in individuals' lives but rather a process occurring within a specific social context. Structural factors and the sense of acceptance and belonging are essential in supporting the transformation. Treatment achievements and the risk for relapse vary over time, so the objectives of the treatment plan must account for characteristics of the pre-treatment stage and the availability and capacity of individuals to restructure their social network, besides the opioid maintenance treatment and institutional social care.
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Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Humanos , Motivación , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prevención SecundariaRESUMEN
BACKGROUND AND AIMS: Mitochondrial swelling is involved in the pathogenesis of many human diseases associated with oxidative stress including obesity. One of the strategies for prevention of deleterious effects related to obesity and overweight is engaging in regular physical activity, of which high intensity interval training (HIIT) is efficient in promoting biogenesis and improving the function of mitochondria. Therefore, our aims were to investigate the effects of HIIT on metabolic and neuro-cardiovascular dynamic control and mitochondrial swelling induced by high-fat diet (HFD). METHODS AND RESULTS: Twenty-three male Wistar rats (60 - 80g) were divided into 4 subgroups: control (C), HIIT, HFD and HFD+HIIT. The whole experimentation period lasted for 22 weeks and HIIT sessions were performed 5 days a week during the last 4 weeks. At the end of the experiments, fasting glucose and insulin tolerance tests were performed. Cerebral microcirculation was analyzed using cortical intravital microscopy for capillary diameter and functional density. Cardiac function and ergoespirometric parameters were also investigated. Mitochondrial swelling was evaluated on brain and heart extracts. HFD promoted an increase on body adiposity (p<0.001), fasting glucose levels (p<0.001), insulin resistance index (p<0.05), cardiac hypertrophy index (p<0.05) and diastolic blood pressure (p<0.05), along with worsened cardiac function (p<0.05), reduced functional cerebral capillary density (p<0.05) and its diameter (p<0.01), and heart and brain mitochondrial function (p<0.001). HFD did not affect any ergoespirometric parameter. After 4 weeks of training, HIIT was able to improve cardiac hypertrophy index, diastolic blood pressure, cerebral functional capillary density (p<0.01) and heart and brain mitochondrial swelling (p<0.001). CONCLUSION: In animals subjected to HFD, HIIT ameliorated both cerebral mitochondrial swelling and functional capillary density, but it did not improve cardiovascular function suggesting that the cardiovascular dysfunction elicited by HFD was not due to heart mitochondrial swelling.
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Sistema Cardiovascular/patología , Dieta Alta en Grasa , Mitocondrias/fisiología , Condicionamiento Físico Animal , Adiposidad , Animales , Glucemia/análisis , Presión Sanguínea , Prueba de Tolerancia a la Glucosa , Hemodinámica , Hipertrofia/patología , Resistencia a la Insulina , Masculino , Microcirculación , Obesidad/metabolismo , Obesidad/patología , Ratas , Ratas WistarRESUMEN
The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-κB p50/50. Herein, we demonstrated the occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L. major-infected macrophages. The parasite intracellular load was reduced in HDAC1 knocked-down macrophages, which presented increased nitric oxide levels. HDAC1 silencing led to the occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification. Importantly, the immunostaining of skin samples from hiporeactive cutaneous leishmaniasis patients infected with L. amazonensis, revealed high levels of HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which contribute to parasite survival and is associated to hiporeactive stage found in L. amazonensis infected patients.
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Histona Desacetilasa 1/metabolismo , Leishmania braziliensis/fisiología , Leishmaniasis Cutánea/inmunología , Macrófagos/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Piel/patología , Adolescente , Adulto , Células Cultivadas , Niño , Extinción Biológica , Femenino , Histona Desacetilasa 1/genética , Interacciones Huésped-Parásitos , Humanos , Evasión Inmune , Leishmaniasis Cutánea/genética , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Carga de Parásitos , Regiones Promotoras Genéticas/genética , Unión Proteica , ARN Interferente Pequeño/genética , Factor de Transcripción Sp1/metabolismo , Adulto JovenRESUMEN
Leishmania parasites utilize adaptive evasion mechanisms in infected macrophages to overcome host defenses and proliferate. We report here that the PERK/eIF2α/ATF4 signaling branch of the integrated endoplasmic reticulum stress response (IERSR) is activated by Leishmania and this pathway is important for Leishmania amazonensis infection. Knocking down PERK or ATF4 expression or inhibiting PERK kinase activity diminished L. amazonensis infection. Knocking down ATF4 decreased NRF2 expression and its nuclear translocation, reduced HO-1 expression and increased nitric oxide production. Meanwhile, the increased expression of ATF4 and HO-1 mRNAs were observed in lesions derived from patients infected with the prevalent related species L.(V.) braziliensis. Our data demonstrates that Leishmania parasites activate the PERK/eIF2α/ATF-4 pathway in cultured macrophages and infected human tissue and that this pathway is important for parasite survival and progression of the infection.
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Factor de Transcripción Activador 4/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Leishmaniasis Cutánea/patología , Factor de Transcripción Activador 4/antagonistas & inhibidores , Factor de Transcripción Activador 4/genética , Animales , Estrés del Retículo Endoplásmico , Células HEK293 , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Humanos , Leishmania/patogenicidad , Leishmaniasis Cutánea/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Macrófagos/parasitología , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico/metabolismo , Fosforilación , Células RAW 264.7 , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
We aimed to analyze the impact of several parenting factors on the relationship between psychopathy and antisocial behavior. Nine hundred youths and their mothers reported on parent-youth interactions, and youth self-report measures of psychopathy, delinquency and violent behavior were taken. Multiple regression was used to test for the significance of interactions between parenting and psychopathy scores. In terms of delinquency, linear interactions between psychopathy and the level of conflict with parents and parents' knowledge of their youths' whereabouts/youths' willingness to disclose information were found based on the data reported by the youths. Data reported by mothers indicated a linear interaction between psychopathy and parents' knowledge/youth disclosure, and a quadratic interaction of conflict with parents. For violence, we used logistic regression models to analyze moderation. No interaction effects between psychopahy scores and parenting factors were found. Youths' reports of high conflict with parents and parents' knowledge/youth disclosure showed to have an impact on violence regardless of the level of psychopathic traits. Implications for the prevention and treatment are discussed.
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Conducta del Adolescente/psicología , Agresión/psicología , Trastorno de Personalidad Antisocial/psicología , Responsabilidad Parental/psicología , Padres/psicología , Adolescente , Femenino , Humanos , Masculino , Relaciones Padres-Hijo , Autoinforme , Violencia/psicologíaRESUMEN
Leishmania amazonensis activates the NF-κB transcriptional repressor homodimer (p50/p50) and promotes nitric oxide synthase (iNOS) downregulation. We investigated the role of PI3K/Akt in p50/p50 NF-κB activation and the effect on iNOS expression in L. amazonensis infection. The increased occupancy of p50/p50 on the iNOS promoter of infected macrophages was observed and we demonstrated that both p50/p50 NF-κB induction and iNOS downregulation in infected macrophages depended on PI3K/Akt activation. Importantly, the intracellular growth of the parasite was also impaired during PI3K/Akt signalling inhibition and in macrophages knocked-down for Akt 1 expression. It was also observed that the increased nuclear levels of p50/p50 in L. amazonensis-infected macrophages were associated with reduced phosphorylation of 907 Ser p105, the precursor of p50. Corroborating these data, we demonstrated the increased levels of phospho-9 Ser GSK3ß in infected macrophages, which is associated with GSK3ß inhibition and, consequently, its inability to phosphorylate p105. Remarkably, we found that the levels of pPTEN 370 Ser, a negative regulator of PI3K, increased due to L. amazonensis infection. Our data support the notion that PI3K/Akt activity is sustained during the parasite infection, leading to NF-κB 105 phosphorylation and further processing to originate p50/p50 homodimers and the consequent downregulation of iNOS expression.
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Leishmania/fisiología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Línea Celular , Dimerización , Regulación hacia Abajo , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Leishmania/genética , Leishmaniasis/metabolismo , Leishmaniasis/parasitología , Leishmaniasis/patología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/química , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , ARN Interferente Pequeño/metabolismo , Transducción de SeñalRESUMEN
Little is known about adult outcomes of males who as adolescents sought treatment for alcohol misuse or drug use, and who additionally were engaging or not engaging in other forms of delinquency. Since the rates of negative outcomes vary in the general population, the study determined whether the sub-groups of clinic attendees fared differently as compared to males of the same age who had not sought treatment for substance misuse from age 21 to 45. Adolescent males who consulted the only substance misuse clinic in a Swedish city between 1968 and 1971 were divided into four groups: ALCOHOL no drug use, no criminal offending (n=52); ALCOHOL+D no drug use, plus criminal offending (n=105); DRUG use, no criminal offending (n=92); and DRUG+D plus criminal offending (n=474). These four groups were compared to a general population sample (GP) of males matched on age and birthplace, who did not seek treatment for SM in adolescence. National Swedish registers provided data on death, hospitalizations for substance misuse (SM), mental and physical disorders, and criminal convictions. Compared to the GP, and after controlling for co-occurring adult outcomes, ALCOHOL showed elevated risks for SM hospitalization and convictions for violent crimes, and DRUG showed elevated risks for SM hospitalization, convictions for non-violent crimes, and hospitalization for psychosis. ALCOHOL+D and DRUG+D showed increased risk for SM hospitalization, violent and non-violent convictions, and DRUG+D additionally, for death, and hospitalizations for psychosis and physical illness. Misuse of alcohol without drug use or other delinquency in adolescence was associated with increased risk for convictions for violent crimes during the subsequent 25 years, in addition to SM, while adolescent drug use without other forms of delinquency was associated with increased risks for convictions for non-violent crimes, hospitalizations for SM, and non-affective psychosis. Cannabis use, with and without delinquency, was associated with subsequent hospitalization for non-affective psychosis. Consistent with contemporary studies, most adolescents treated for SM from 1968-1971 presented delinquency that was associated with an increase in risk of all adverse outcomes to age 45.
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Conducta del Adolescente , Criminales/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Delincuencia Juvenil/estadística & datos numéricos , Trastornos Psicóticos/epidemiología , Sistema de Registros/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Violencia/estadística & datos numéricos , Adolescente , Adulto , Alcoholismo/epidemiología , Humanos , Masculino , Abuso de Marihuana/epidemiología , Persona de Mediana Edad , Mortalidad , Suecia/epidemiología , Adulto JovenRESUMEN
The aim of this exploratory study was twofold. First, the severity of physical and emotional abuse perpetrated by parents and its association with internalizing and externalizing problems were explored in a sample of 104 male and female youth offenders. Second, we tested the moderate effect of callous-unemotional traits on the relation between physical and emotional victimization and internalizing and externalizing problems in boys. The analyses revealed that a high percentage of youth offenders reported having been physically abused. More severe physical abuse was not related to higher levels of internalizing or externalizing problems. Young offenders' emotional abuse levels were low; however, this type of abuse was positively associated with externalizing problems among boys, regardless of the level of callous-unemotional traits. Thus, we suggest that youth offenders must be assessed using measures of physical and emotional abuse, and their case management should integrate specific programs to focus on the family environment to which the adolescents will most likely return after their sentence.
Asunto(s)
Trastorno de Personalidad Antisocial/psicología , Maltrato a los Niños/psicología , Control Interno-Externo , Delincuencia Juvenil/psicología , Prisioneros/psicología , Adolescente , Trastorno de Personalidad Antisocial/rehabilitación , Manejo de Caso , Maltrato a los Niños/rehabilitación , Violencia Doméstica , Femenino , Humanos , Delincuencia Juvenil/rehabilitación , Masculino , Determinación de la Personalidad , Quebec , Factores de RiesgoRESUMEN
BACKGROUND: Chemotherapy for leishmaniasis, a disease caused by Leishmania parasites, is expensive and causes side effects. Furthermore, parasite resistance constitutes an increasing problem, and new drugs against this disease are needed. In this study, we examine the effect of the compound 8,10,18-trihydroxy-2,6-dolabelladiene (Dolabelladienetriol), on Leishmania growth in macrophages. The ability of this compound to modulate macrophage function is also described. METHODOLOGY/PRINCIPAL FINDINGS: Leishmania-infected macrophages were treated with Dolabelladienetriol, and parasite growth was measured using an infectivity index. Nitric oxide (NO), TNF-α and TGF-ß production were assayed in macrophages using specific assays. NF-kB nuclear translocation was analyzed by western blot. Dolabelladienetriol inhibited Leishmania in a dose-dependent manner; the IC(50) was 44 µM. Dolabelladienetriol diminished NO, TNF-α and TGF-ß production in uninfected and Leishmania-infected macrophages and reduced NF-kB nuclear translocation. Dolabelladienetriol inhibited Leishmania infection even when the parasite growth was exacerbated by either IL-10 or TGF-ß. In addition, Dolabelladienetriol inhibited Leishmania growth in HIV-1-co-infected human macrophages. CONCLUSION: Our results indicate that Dolabelladienetriol significantly inhibits Leishmania in macrophages even in the presence of factors that exacerbate parasite growth, such as IL-10, TGF-ß and HIV-1 co-infection. Our results suggest that Dolabelladienetriol is a promising candidate for future studies regarding treatment of leishmaniasis, associated or not with HIV-1 infection.
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Antiprotozoarios/farmacología , Extractos Celulares/farmacología , Diterpenos/farmacología , Leishmania/efectos de los fármacos , Phaeophyceae/química , Animales , Antiprotozoarios/aislamiento & purificación , Extractos Celulares/aislamiento & purificación , Células Cultivadas , Diterpenos/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Leishmania/crecimiento & desarrollo , Macrófagos/inmunología , Macrófagos/parasitología , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Pruebas de Sensibilidad Parasitaria , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
While many studies have observed a positive association between maltreatment in childhood and criminality in adolescence and adulthood, others have failed to detect such an association. Most studies, however, have not examined different types of maltreatment, nor taken account of other family and childhood factors that are predictive of criminality. Using data from a prospective, longitudinal investigation of a community sample of 1,037 males, we calculated hierarchical logistic regression models to estimate the associations of boys' self-reports of neglect, emotional abuse, and physical abuse at ages 10 and 12, with convictions for criminal offenses from age 12 to 24, after taking account of conduct problems, hurtful and uncaring behaviours (HUB), and parent's criminality. At ages 10 and 12, boys' reports of neglect, emotional abuse, and physical abuse, were not associated with criminal convictions for non-violent or for violent crimes from age 12 to 24. Among boys who did not engage in HUB towards others reports of emotional abuse were associated with subsequent criminality, while this association disappeared among the boys engaging in such behaviours. In this community sample of males, levels of each type of maltreatment were low and there were no direct associations with subsequent criminal convictions. The findings add to emerging evidence that the characteristics of the child and parents, as well as the type of maltreatment modify the association with future criminal offending.
Asunto(s)
Conducta del Adolescente/psicología , Maltrato a los Niños/psicología , Trastorno de la Conducta/psicología , Criminales/psicología , Violencia/psicología , Poblaciones Vulnerables/psicología , Adolescente , Niño , Trastorno de la Conducta/diagnóstico , Humanos , Estudios Longitudinales , Masculino , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Adulto JovenRESUMEN
BACKGROUND: Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. METHODS: From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-alpha, IL-1alpha were searched and quantified. RESULTS: We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the expression of these molecules ranged from absent to medium intensity. It was not observed any correlation between severity of the disease and these markers. There was a correlation between the number of Leishmania antigen positive cells and CD4+ T cells, and between the number of CD4+ T cells and CD8+ T cells. In dogs presenting different histopathological patterns of glomerulonephritis, parameters of proliferation and apoptosis were studied. Ki-67, a proliferative marker, was not detected locally, but fewer apoptotic cells and lower TNF-alpha expression were seen in infected animals than in non-infected controls. CONCLUSION: Immunopathogenic mechanisms of VL glomerulonephritis are complex and data in the present study suggest no clear participation of immunoglobulin and C3b deposits in these dogs but the possible migration of CD4+ T cells into the glomeruli, participation of adhesion molecules, and diminished apoptosis of cells contributing to determine the proliferative pattern of glomerulonephritis in VL.
Asunto(s)
Apoptosis , Linfocitos T CD4-Positivos/inmunología , Moléculas de Adhesión Celular/inmunología , Enfermedades de los Perros/inmunología , Glomerulonefritis/inmunología , Leishmaniasis Visceral/veterinaria , Animales , Perros , Enfermedades del Complejo Inmune/inmunología , Inmunohistoquímica , Riñón/patología , Leishmania infantum/inmunología , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/inmunología , MicroscopíaRESUMEN
Host invasion by pathogens is frequently associated with the activation of nuclear factor kappaB (NF-kappaB), which modulates the expression of genes involved in the immunological response of the host. However, pathogens may also subvert these mechanisms to secure their survival. We describe the effect of Leishmania amazonensis infection on NF-kappaB transcriptional factor activation in macrophages and the subsequent reduction in inducible nitric oxide synthase (iNOS) expression. L. amazonensis promastigote infection activates the p50/p50 NF-kappaB complex, a classic transcriptional repressor. Interestingly, L. amazonensis promotes the change of the classical p65/p50 NF-kappaB dimer induced by LPS, leading to the p50/p50 NF-kappaB complex activation in macrophages stimulated with LPS. Moreover, this parasite promotes the reduction of p65 total levels in infected macrophages. All these effects contribute to the observation that this parasite is able to restrain the NF-kappaB-dependent transcriptional activity induced by LPS. Strikingly, L. amazonensis reduces the mRNA levels of the iNOS in addition to protein expression and the production of nitric oxide in LPS-stimulated macrophages. Accordingly, as revealed by reporter-gene assays, L. amazonensis-induced iNOS repression requires NF-kappaB sites in the iNOS promoter region. In summary, our results suggest that L. amazonensis has developed an adaptive strategy to escape from host defense by activating the NF-kappaB repressor complex p50/p50. The activation of this specific host transcriptional response negatively regulates the expression of iNOS, favoring the establishment and success of L. amazonensis infection.
Asunto(s)
Leishmania/inmunología , Leishmaniasis/inmunología , Macrófagos/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Animales , Línea Celular , Represión Enzimática , Interacciones Huésped-Patógeno , Humanos , Leishmania/patogenicidad , Leishmaniasis/enzimología , Leishmaniasis/genética , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/patología , Ratones , Subunidad p50 de NF-kappa B/genética , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Activación TranscripcionalRESUMEN
BACKGROUND: To evaluate the prevalence of hepatitis B virus (HBV) and associated factors in 949 heroin users (HU): injectors (IHUs) and non-injectors (NIHUs). METHODS: Cross-sectional study; structured questionnaire administered by computer-assisted personal interviewing and audio computer-assisted self-interviewing; dry blood samples analysed for the hepatitis B core antigen and hepatitis B surface antigen; bivariate analysis and logistic regression. RESULTS: The prevalence of infection was significantly higher in IHUs (22.5%) than in NIHUs (7.4%) in the three cities. In the logistic analysis of male IHUs, infection was found to be associated with living in Seville, age over 25, foreign nationality, having had a sexual partner who traded sex, hepatitis C virus infection, and having injected for more than 5 years. In female IHUs, HBV infection was associated with age over 25, having injected as the first main route of administration, and having begun to inject before 18 years of age. In NIHUs, the associated factors were female gender, foreign nationality and having been tattooed. In young IHUs, the prevalence of HBV infection remains four times higher than in the general population of the same age group. CONCLUSION: The vaccination strategy urgently needs to be reinforced and redesigned to achieve acceptable control of the HBV infection in the most vulnerable groups, with special attention to immigrants.
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Hepatitis B/epidemiología , Hepatitis B/transmisión , Dependencia de Heroína/epidemiología , Jóvenes sin Hogar/estadística & datos numéricos , Asunción de Riesgos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adolescente , Adulto , Áreas de Influencia de Salud , Estudios Transversales , Demografía , Femenino , Humanos , Incidencia , Masculino , Factores de Riesgo , Conducta Sexual , España/epidemiologíaRESUMEN
To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 street-recruited current heroin users aged 18-30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and pre-coded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed.
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Conocimientos, Actitudes y Práctica en Salud , Dependencia de Heroína/psicología , Narcóticos/efectos adversos , Adolescente , Adulto , Computadores , Sobredosis de Droga/psicología , Femenino , Conductas Relacionadas con la Salud , Humanos , Entrevistas como Asunto , Modelos Logísticos , Masculino , Factores de Riesgo , España , Encuestas y Cuestionarios , Salud UrbanaRESUMEN
During Trypanosoma cruzi infection, T cells up-regulate caspase-8 activity. To assess the role of caspase-8 in T cell-mediated immunity, we investigated the effects of caspase-8 inhibition on T cells in viral FLIP (v-FLIP) transgenic mice. Compared with wild-type controls, increased parasitemia was observed in v-FLIP mice infected with T. cruzi. There was a profound decrease in expansion of both CD4 and CD8 T cell subsets in the spleens of infected v-FLIP mice. We did not find differences in activation ratios of T cells from transgenic or wild-type infected mice. However, the numbers of memory/activated CD4 and CD8 T cells were markedly reduced in v-FLIP mice, possibly due to defective survival. We also found decreased production of IL-2 and increased secretion of type 2 cytokines, IL-4 and IL-10, which could enhance susceptibility to infection. Similar, but less pronounced, alterations were observed in mice treated with the caspase-8 inhibitor, zIETD. Furthermore, blockade of caspase-8 by zIETD in vitro mimicked the effects observed on T. cruzi infection in vivo, affecting the generation of activated/memory T cells and T cell cytokine production. Caspase-8 is also required for NF-kappaB signaling upon T cell activation. Blockade of caspase-8 by either v-FLIP expression or treatment with zIETD peptide decreased NF-kappaB responses to TCR:CD3 engagement in T cell cultures. These results suggest a critical role for caspase-8 in the establishment of T cell memory, cell signaling, and regulation of cytokine responses during protozoan infection.