RESUMEN
BACKGROUND: Race and ethnicity classification systems have considerable implications for public health, including the potential to reveal or mask inequities. Given increasing "super-diversity" and multiple racial/ethnic identities in many global settings, especially among younger generations, different ethnicity classification systems can underrepresent population heterogeneity and can misallocate and render invisible Indigenous people and ethnic minorities. We investigated three ethnicity classification methods and their relationship to sample size, socio-demographics and sexual health indicators. METHODS: We examined data from New Zealand's HIV behavioural surveillance programme for men who have sex with men (MSM) in 2006, 2008, 2011, and 2014. Participation was voluntary, anonymous and self-completed; recruitment was via community venues and online. Ethnicity allowed for multiple responses; we investigated three methods of dealing with these: Prioritisation, Single/Combination, and Total Response. Major ethnic groups included Asian, European, indigenous Maori, and Pacific. For each classification method, statistically significant associations with ethnicity for demographic and eight sexual health indicators were assessed using multivariable logistic regression. RESULTS: Overall, 10,525 MSM provided ethnicity data. Classification methods produced different sample sizes, and there were ethnic disparities for every sexual health indicator. In multivariable analysis, when compared with European MSM, ethnic differences were inconsistent across classification systems for two of the eight sexual health outcomes: Maori MSM were less likely to report regular partner condomless anal intercourse using Prioritisation or Total Response but not Single/Combination, and Pacific MSM were more likely to report an STI diagnosis when using Total Response but not Prioritisation or Single/Combination. CONCLUSIONS: Different classification approaches alter sample sizes and identification of health inequities. Future research should strive for equal explanatory power of Indigenous and ethnic minority groups and examine additional measures such as socially-assigned ethnicity and experiences of discrimination and racism. These findings have broad implications for surveillance and research that is used to inform public health responses.
Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Etnicidad , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Grupos Minoritarios , Salud Pública , Conducta Sexual , Parejas SexualesRESUMEN
Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival- and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities.
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Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Relaxina/metabolismo , Animales , Antineoplásicos/farmacología , Progresión de la Enfermedad , Humanos , Masculino , Terapia Molecular Dirigida/métodos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Understanding HIV testing behaviour is vital to developing evidence-based policy and programming that supports optimal HIV care, support, and prevention. This has not been investigated among younger gay, bisexual, and other men who have sex with men (YMSM, aged 16-29) in New Zealand. METHODS: National HIV sociobehavioural surveillance data from 2006, 2008, and 2011 was pooled to determine the prevalence of recent HIV testing (in the last 12 months) among YMSM. Factors associated with recent testing were determined using manual backward stepwise multivariate logistic regression. RESULTS: Of 3,352 eligible YMSM, 1,338 (39.9%) reported a recent HIV test. In the final adjusted model, the odds of having a recent HIV test were higher for YMSM who were older, spent more time with other gay men, reported multiple sex partners, had a regular partner for 6-12 months, reported high condom use with casual partners, and disagreed that HIV is a less serious threat nowadays and that an HIV-positive man would disclose before sex. The odds of having a recent HIV test were lower for YMSM who were bisexual, recruited online, reported Pacific Islander or Asian ethnicities, reported no regular partner or one for >3 years, were insertive-only during anal intercourse with a regular partner, and who had less HIV-related knowledge. CONCLUSION: A priority for HIV management should be connecting YMSM at risk of infection, but unlikely to test with appropriate testing services. New generations of YMSM require targeted, culturally relevant health promotion that provides accurate understandings about HIV transmission and prevention.
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Serodiagnóstico del SIDA/estadística & datos numéricos , Bisexualidad/estadística & datos numéricos , Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina/estadística & datos numéricos , Tamizaje Masivo/estadística & datos numéricos , Adolescente , Adulto , Promoción de la Salud/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Nueva Zelanda , Vigilancia de la Población , Prevalencia , Sexo Seguro/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Parejas Sexuales , Adulto JovenRESUMEN
OBJECTIVES: To investigate the effect of cooking with an iron ingot on the iron content of several water and Cambodian food preparations. METHODS: Various food and water samples were prepared, in replicate, in glass and aluminium pots with and without an iron ingot. The samples were subjected to iron content analysis using standard ICP-OES procedures. RESULTS: Prepared with an ingot, the iron content was 76.3 µg iron/g higher in lemon water, 32.6 µg iron/g higher in pork soup and 3.3 µg iron/g higher in fish soup, than in the same foods prepared without an ingot. Acidity of the food samples was positively associated with iron leaching. CONCLUSIONS: Even when taking into account the low bioavailability of contaminant iron, approximately 75% of the daily iron requirement can be met by consuming 1L of lemon water prepared with an iron ingot. Its use may be a cheap and sustainable means of improving iron intake for those with iron-deficient diets.
Asunto(s)
Culinaria/métodos , Análisis de los Alimentos , Hierro/análisis , Oligoelementos/análisis , Agua/análisis , Aluminio , Cambodia , Utensilios de Comida y Culinaria , Vidrio , HumanosRESUMEN
BACKGROUND: More than 3.5 billion people are affected by iron-deficiency anaemia (IDA). Previous studies have shown that the use of iron pots in daily cooking ameliorates IDA. We report a study on the use of a novel treatment to address IDA in rural women in Cambodia, where the use of iron pots is not common. METHODS: A community-wide randomized controlled trial was conducted in the village of Preak Ruessei, Kandal Province, Cambodia. Rural women (n = 189) were enrolled and randomly assigned by household to one of three groups: (i) control, (ii) iron treatment with no follow-up and (iii) iron treatment with follow-up visits to provide IDA education. Haemoglobin, serum iron and C-reactive protein concentrations were measured at baseline, 3 and 6 months. A reusable fish-shaped iron ingot was distributed to the two treatment groups and participants were directed to use them daily for cooking. We hypothesized that iron from the ingot would leach iron into food providing an effective iron source. RESULTS: Blood iron levels were higher in women in the iron fish plus follow-up at 3 months compared with controls, but this was not maintained. At 6 months, haemoglobin and serum iron had fallen in all groups and the proportion of anaemic women had increased. CONCLUSIONS: This study shows that the iron ingot was effective in the short but not longer-term against IDA. Though a novel treatment option, further research is warranted to determine bioavailability of leached iron and whether or not the surface area is large enough for sufficient iron leaching.
Asunto(s)
Anemia Ferropénica/terapia , Culinaria/métodos , Suplementos Dietéticos , Hierro/uso terapéutico , Salud Rural , Adulto , Anemia Ferropénica/epidemiología , Proteína C-Reactiva/análisis , Cambodia/epidemiología , Femenino , Hemoglobinas/análisis , Humanos , Hierro/administración & dosificación , Estudios Longitudinales , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Factores SocioeconómicosRESUMEN
The Foresight Report, published in 2007, provided a vision for the future of the veterinary profession. Many of the directions set in the report have already been remarkably accurate, but fiscal constraints stemming from the global recession that began in 2008 will have a significant impact on academia and on the future of the veterinary profession. Three primary forces will shape veterinary education in the coming decade: (1) the urgent need to lead an integrated approach to animal, human, and environmental health; (2) the continued information explosion; and (3) the challenge of delivering high-quality veterinary clinical training at a time of fiscal restraint. Despite economic woes and financial pressure, this is the time to rethink veterinary medical education. This article outlines these challenges and suggests ways to continue to evolve veterinary education.
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Educación en Veterinaria/tendencias , Innovación Organizacional , Educación en Veterinaria/métodos , Salud Ambiental , Humanos , Comunicación Interdisciplinaria , Modelos Educacionales , Práctica de Salud Pública , Facultades de Medicina VeterinariaRESUMEN
OBJECTIVES: To assess trends in sexual health outcomes among men who have sex with men (MSM) disaggregated by ethnicity. DESIGN: Repeated cross-sectional. SETTING: Behavioural surveillance data from 2006, 2008, 2011 and 2014 were collected in-person and online across Aotearoa New Zealand. PARTICIPANTS: Eligible participants were self-identified men aged 16 years or older who reported sex with another man in the past 5 years. We classified 10 525 participants' ethnicities: Asian (n=1003, 9.8%), Maori (Indigenous people of Aotearoa New Zealand, n=1058, 10.3%), Pacific (n=424, 4.1%) and European (n=7867, 76.8%). OUTCOME MEASURES: The sexual health outcomes examined were >20 recent (past 6 months) male sexual partners, past-year sexually transmitted infection (STI) testing, past-year STI diagnosis, lifetime and past-year HIV testing, lifetime HIV-positive diagnosis and any recent (past 6 months) condomless anal intercourse with casual or regular partners. RESULTS: When disaggregated, Indigenous and ethnic minority groups reported sexual health trends that diverged from the European MSM and each other. For example, Asian MSM increased lifetime HIV testing (adjusted OR, AOR=1.31 per survey cycle, 95% CI 1.17 to 1.47) and recent HIV testing (AOR=1.14, 95% CI 1.02 to 1.28) with no changes among Maori MSM or Pacific MSM. Condomless anal intercourse with casual partners increased among Maori MSM (AOR=1.13, 95% CI 1.01 to 1.28) with no changes for Asian or Pacific MSM. Condomless anal intercourse with regular partners decreased among Pacific MSM (AOR=0.83, 95% CI 0.69 to 0.99) with no changes for Asian or Maori MSM. CONCLUSIONS: Population-level trends were driven by European MSM, masking important differences for Indigenous and ethnic minority sub-groups. Surveillance data disaggregated by ethnicity highlight inequities in sexual health service access and prevention uptake. Future research should collect, analyse and report disaggregated data by ethnicity to advance health equity.
Asunto(s)
Infecciones por VIH , Salud Sexual , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Adolescente , Estudios Transversales , Etnicidad , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Grupos Minoritarios , Nueva Zelanda/epidemiología , Asunción de Riesgos , Conducta Sexual , Parejas Sexuales , Enfermedades de Transmisión Sexual/epidemiologíaRESUMEN
Hormone antagonists can be effective tools to delineate receptor signaling pathways and their resulting downstream physiological actions. Mutation of the receptor binding domain (RBD) of human H2 relaxin (deltaH2) impaired its biological function as measured by cAMP signaling. In a competition assay, deltaH2 exhibited antagonistic activity by blocking recombinant H2 relaxin from binding to receptors on THP-1 cells. In a flow cytometry-based binding assay, deltaH2 demonstrated weak binding to 293T cells expressing the LGR7 receptor in the presence of biotinylated H2 relaxin. When human prostate cancer cell lines (PC-3 and LNCaP) were engineered to overexpress eGFP, wild-type (WT) H2, or deltaH2, and subsequently implanted into NOD/SCID mice, tumor xenografts overexpressing deltaH2 displayed smaller volumes compared to H2 and eGFP controls. Plasma osmolality readings and microvessel density and area assessment suggest that deltaH2 modulates physiological parameters in vivo. In a second murine model, intratumoral injections of lentivectors engineered to express deltaH2/eGFP led to suppressed tumor growth compared to controls. This study provides further evidence supporting a role for H2 relaxin in prostate tumor growth. More importantly, we report how mutation of the H2 relaxin RBD confers the hormone derivative with antagonistic properties, offering a novel reagent for relaxin research.
Asunto(s)
Neoplasias de la Próstata/prevención & control , Relaxina/uso terapéutico , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones SCID , Trasplante de Neoplasias , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/prevención & control , Neoplasias de la Próstata/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
UNLABELLED: Background Condom promotion remains a cornerstone of HIV/STI control, but must be informed by evidence of uptake and address disparities in use. This study sought to determine the prevalence of, and demographic, behavioural and relational factors associated with, condom use during insertive and receptive anal intercourse with casual partners among younger gay, bisexual and other men who have sex with men (YMSM) in New Zealand. METHODS: The 2006-2011 national HIV behavioural surveillance data for YMSM aged 16-29 years was pooled. Separately for each sexual position, frequent (always/almost always) versus infrequent condom use was regressed onto explanatory variables using manual backward stepwise multivariable logistic regression analysis. RESULTS: Three-quarters of YMSM reported frequent condom use during insertive (76.0%) and receptive (73.8%) anal intercourse. YMSM who were exclusively insertive were more likely to report frequent condom use than versatile YMSM. Factors positively associated with frequent condom use, irrespective of sexual position were: in-person versus web-based recruitment, testing HIV negative versus never testing or testing HIV positive, having no recent sex with women, reporting two to five versus one male sexual partner in the past 6 months, reporting no current regular partner, but if in a regular relationship, reporting a boyfriend-type versus fuckbuddy-type partner, and frequent versus infrequent regular partner condom use. Pacific ethnicity and less formal education were negatively associated with frequent condom use only during receptive anal intercourse. CONCLUSIONS: The findings from this study demonstrate that condom norms can be actively established and maintained among YMSM. Condom promotion efforts must increase YMSM's capacity, agency and skills to negotiate condom use, especially for the receptive partner.
Asunto(s)
Bisexualidad , Condones , Homosexualidad Masculina , Conducta Sexual , Adolescente , Adulto , Infecciones por VIH , Humanos , Masculino , Nueva Zelanda , Parejas Sexuales , Minorías Sexuales y de Género , Adulto JovenRESUMEN
A recombinant adenovirus containing the human H2 preprorelaxin (hH2) cDNA and a reporter gene was coinjected with a transactivator virus (Ad-tTA) into the lateral cerebral ventricles of female rats. Cardiovascular effects were measured over a 21-day period. Circulating vasopressin in the periphery was significantly greater (P < .0001) in the relaxin-treated group throughout the experimental period, compared with controls. There was a significant decrease in plasma osmolality (P < .05) by approximately 10 mmol/L in the treated group by day 14. Immunofluorescence for hH2 present in cryosections showed rAd transduction and hH2 expression from ependymal cells of the ventricular system. Adenovirus-mediated delivery of hH2 to the brain is capable of producing bioactive relaxin that affects cardiovascular parameters.
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Expresión Génica , Relaxina/genética , Relaxina/metabolismo , Adenoviridae/genética , Animales , Humanos , Concentración Osmolar , Precursores de Proteínas/genética , Ratas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factores de Tiempo , Vasopresinas/sangreRESUMEN
Iron deficiency and associated anemia are severe public health problems, which are prevalent in the developing world. We conducted a cross-sectional survey, comprised of written interview questions and laboratory analysis of blood biomarkers, in Kandal Province, Cambodia. The objective of this study is to examine possible factors that are associated with anemia in rural Cambodia. Data on socioeconomic status, water source/treatment practices, and meat consumption was also collected. Of the 297 women surveyed, 51.2% were anemic. Of those women found to be anemic, iron deficiency was implicated in 9.7% of cases (SF <15 ng/L), with an additional 18.5% reported to be borderline iron deficient (serum ferritin=15-30 ng/L). Meat consumption was very low, with nearly one-half of the women consuming meat one time per month or less. This study highlights the multi-faceted etiology of anemia in Cambodia and emphasizes the need for comprehensive nutrition surveying in order to better inform prevention and treatment programming and policy development.
Asunto(s)
Anemia Ferropénica/epidemiología , Población Rural , Clase Social , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Cambodia/epidemiología , Estudios Transversales , Dieta , Femenino , Ferritinas/sangre , Hemoglobinas/análisis , Humanos , Hierro de la Dieta/administración & dosificación , Carne , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Abastecimiento de AguaRESUMEN
Main partners are a common source of new HIV infections among men who have sex with men (MSM). National behavioral surveillance data (2006-2011) for younger MSM (YMSM, aged 16-29) in New Zealand were analyzed to investigate condom use during anal intercourse with a regular partner (boyfriend/fuckbuddy) by sexual position (insertive/receptive). Backward-stepwise multivariate multinomial logistic regression was used to identify demographic, relational, behavioral, and cognitive factors associated with condom use frequency (high, medium, low). Most YMSM who reported a current regular partner (n=1,221) classified them as a boyfriend (59.5%) versus fuckbuddy (40.5%), though condom use was higher with the latter partner type. Condom use or nonuse was habitual across partners, although insertive sexual position was positively associated with condom use. YMSM who believed condoms reduce sensitivity reported lower condom use. Condoms remain the leading HIV/STI prevention tool for YMSM; efforts to improve condom use must consider sexual position and relationship factors.
Asunto(s)
Bisexualidad/psicología , Condones/estadística & datos numéricos , Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina/psicología , Parejas Sexuales , Adolescente , Adulto , Factores de Edad , Encuestas Epidemiológicas , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Nueva Zelanda , Factores de Riesgo , Asunción de Riesgos , Sexo Seguro , Conducta Sexual , Encuestas y CuestionariosRESUMEN
The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke.
Asunto(s)
Infarto de la Arteria Cerebral Media/prevención & control , Relaxina/uso terapéutico , Animales , Astrocitos/efectos de los fármacos , Encéfalo/patología , Células Cultivadas , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Infarto de la Arteria Cerebral Media/patología , Masculino , Distribución Aleatoria , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores de Péptidos/agonistas , Receptores de Péptidos/antagonistas & inhibidores , Proteínas Recombinantes/uso terapéutico , Relaxina/farmacologíaRESUMEN
This study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.
Asunto(s)
Adenoviridae/genética , Neoplasias Mamarias Animales/patología , Invasividad Neoplásica , Precursores de Proteínas/genética , Relaxina/genética , Animales , Western Blotting , División Celular , Línea Celular , Movimiento Celular , Medios de Cultivo Condicionados/química , Perros , Expresión Génica , Vectores Genéticos , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/genética , Espectrometría de Masas , Monocitos/metabolismo , Precursores de Proteínas/análisis , Precursores de Proteínas/fisiología , Proteínas Recombinantes/análisis , Relaxina/análisis , Relaxina/fisiología , TransfecciónRESUMEN
The peptide relaxin has recently been shown to protect brain tissues from the detrimental effects of ischemia. To date, the mechanisms for this remain unclear. In order to investigate the neuroprotective mechanisms by which relaxin may protect the brain, we investigated the possibility that relaxin protects astrocytes from hypoxia or oxygen/glucose deprivation (OGD). Cultured astrocytes were pre-treated with either relaxin-2 or relaxin-3 and exposed to OGD for 24 or 48 hours. Following OGD exposure, viability assays showed that relaxin-treated cells exhibited a higher viability when compared to astrocytes that experienced OGD-alone. Next, to test whether relaxin reduced the production of reactive oxygen species (ROS) astrocytes were exposed to the same conditions as the previous experiment and a commercially available ROS detection kit was used to detect ROS production. Astrocytes that were treated with relaxin-2 and relaxin-3 showed a marked decrease in ROS production when compared to control astrocytes that were exposed only to OGD. Finally, experiments were performed to determine whether or not the mitochondrial membrane potential was affected by relaxin treatment during 24 hour OGD. Mitochondrial membrane potential was higher in astrocytes that were treated with relaxin-2 and relaxin-3 compared to untreated OGD-alone astrocytes. Taken together, these data present novel findings that show relaxin protects astrocytes from ischemic conditions through the reduction of ROS production and the maintenance of mitochondrial membrane potential.
Asunto(s)
Astrocitos/citología , Astrocitos/efectos de los fármacos , Citoprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Relaxina/farmacología , Animales , Apoptosis/efectos de los fármacos , Astrocitos/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Glucosa/deficiencia , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Óxido Nítrico/metabolismo , Oxígeno , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Androgen hormones and the androgen receptor (AR) pathway are the main targets of anti-hormonal therapies for prostate cancer. However, resistance inevitably develops to treatments aimed at the AR pathway resulting in androgen-independent or hormone-refractory prostate cancer (HRPC). Therefore, there is a significant unmet need for new, non-androgen anti-hormonal strategies for the management of prostate cancer. We demonstrate that a relaxin hormone receptor antagonist, AT-001, an analog of human H2 relaxin, represents a first-in-class anti-hormonal candidate treatment designed to significantly curtail the growth of androgen-independent human prostate tumor xenografts. Chemically synthesized AT-001, administered subcutaneously, suppressed PC3 xenograft growth by up to 60%. AT-001 also synergized with docetaxel, standard first-line chemotherapy for HRPC, to suppress tumor growth by more than 98% in PC3 xenografts via a mechanism involving the downregulation of hypoxia-inducible factor 1 alpha and the hypoxia-induced response. Our data support developing AT-001 for clinical use as an anti-relaxin hormonal therapy for advanced prostate cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores de Péptidos/antagonistas & inhibidores , Taxoides/farmacología , Animales , Apoptosis/efectos de los fármacos , Unión Competitiva , Western Blotting , Proliferación Celular/efectos de los fármacos , Docetaxel , Sinergismo Farmacológico , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In Cambodia, both anaemia and vitamin A deficiency are serious health problems. Despite this, few comprehensive nutritional surveys have been completed to date. This study evaluates the adequacy of iron and vitamin A intakes, as well as women's nutritional knowledge in rural Kandal province. Twenty-four hour recalls, pile sort activities, socioeconomic surveys, focus groups, and market surveys were carried out with 67 women from 5 villages in rural Kandal Province. Ninety seven percent of women did not meet their daily-recommended intake of iron, while 70% did not meet their daily-recommended intake of vitamin A. Although many women consume vitamin A-rich and iron rich-foods daily, they do not consume large enough quantities of these foods. Results suggest that both the cost of foods as well as the extent of health knowledge is linked to nutritional practice. Most animal-source iron and vitamin A-rich foods are considered expensive; however, small fish, and several plant-source vitamin A-rich foods are inexpensive and easy to access. Despite health education, food restrictions lead some healthy foods to be considered to be harmful to women. Ultimately, this study demonstrates the importance of developing comprehensive nutritional interventions in Cambodia. Health programming must provide women with not only suggestions to include low-cost nutrient-rich foods, but also advise them about the quantities that are likely to have an impact on nutritional status. Programs should take a community-based, inter-sectoral approach that simultaneously combines culturally informed health education with initiatives that combat poverty and increase access to nutrient rich foods.
Asunto(s)
Dieta/métodos , Conocimientos, Actitudes y Práctica en Salud , Encuestas Nutricionales/métodos , Estado Nutricional/fisiología , Población Rural/estadística & datos numéricos , Adulto , Anciano , Anemia/epidemiología , Cambodia/epidemiología , Dieta/estadística & datos numéricos , Registros de Dieta , Ingestión de Energía/fisiología , Femenino , Grupos Focales , Humanos , Hierro de la Dieta/administración & dosificación , Persona de Mediana Edad , Encuestas Nutricionales/estadística & datos numéricos , Pobreza/estadística & datos numéricos , Factores Socioeconómicos , Vitamina A/administración & dosificación , Deficiencia de Vitamina A/epidemiología , Adulto JovenRESUMEN
Relaxin produces a sustained decrease in total peripheral resistance, but the effects of relaxin on skeletal muscle arterioles, an important contributor to systemic resistance, are unknown. Using the intact, blood-perfused hamster cremaster muscle preparation in situ, we tested the effects of relaxin on skeletal muscle arteriolar microvasculature by applying 10(-10)âM relaxin to second-, third- and fourth-order arterioles and capillaries. The mechanisms responsible for relaxin-induced dilations were explored by applying 10(-10)âM relaxin to second-order arterioles in the presence of 10(-5)âM N(G)-nitro-l-arginine methyl ester (l-NAME, nitric oxide (NO) synthase inhibitor), 10(-5)âM glibenclamide (GLIB, ATP-dependent potassium (K(+)) channel inhibitor), 10(-3)âM tetraethylammonium (TEA) or 10(-7)âM iberiotoxin (IBTX, calcium-associated K(+) channel inhibitor). Relaxin caused second- (peak change in diameter: 8.3 ± 1.7âµm) and third (4.5 ± 1.1âµm)-order arterioles to vasodilate transiently while fourth-order arterioles did not (0.01 ± 0.04âµm). Relaxin-induced vasodilations were significantly inhibited by l-NAME, GLIB, TEA and IBTX. Relaxin stimulated capillaries to induce a vasodilation in upstream fourth-order arterioles (2.1 ± 0.3âµm), indicating that relaxin can induce conducted responses vasodilation that travels through blood vessel walls via gap junctions. We confirmed gap junction involvement by showing that gap junction uncouplers (18-ß-glycyrrhetinic acid (40 × 10(-6)âM) or 0.07% halothane) inhibited upstream vasodilations to localised relaxin stimulation of second-order arterioles. Therefore, relaxin produces transient NO- and K(+) channel-dependent vasodilations in skeletal muscle arterioles and stimulates capillaries to initiate conducted responses. The transient nature of the arteriolar dilation brings into question the role of skeletal muscle vascular beds in generating the sustained systemic haemodynamic effects induced by relaxin.
Asunto(s)
Arteriolas/fisiología , Microcirculación , Músculo Esquelético/irrigación sanguínea , Relaxina/metabolismo , Vasodilatación , Vasodilatadores/metabolismo , Animales , Cricetinae , Masculino , Mesocricetus , Músculo Esquelético/metabolismoRESUMEN
Anemia is a severe global public health problem with serious consequences for both the human and socio-economic health. This paper presents a situation analysis of the burden of anemia in Cambodia, including a discussion of the country-specific etiologies and future research needs. All available literature on the prevalence and etiology of anemia in Cambodia was collected using standard search protocols. Prevalence data was readily identified for pre-school aged children and women of reproductive age, but there is a dearth of information for school-aged children, men and the elderly. Despite progress in nation-wide programming over the past decade, anemia remains a significant public health problem in Cambodia, especially for women and children. Anemia is a multifaceted disease and both nutritional and non-nutritional etiologies were identified, with iron deficiency accounting for the majority of the burden of disease. The current study highlights the need for a national nutrition survey, including collection of data on the iron status and prevalence of anemia in all population groups. It is impossible to develop effective intervention programs without a clear picture of the burden and cause of disease in the country.
Asunto(s)
Anemia/epidemiología , Anemia/etiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anemia/etnología , Anemia Ferropénica/epidemiología , Anemia Ferropénica/etnología , Anemia Ferropénica/etiología , Cambodia/epidemiología , Niño , Enfermedades Carenciales/epidemiología , Enfermedades Carenciales/etnología , Enfermedades Carenciales/etiología , Enfermedades Carenciales/fisiopatología , Dieta/efectos adversos , Suplementos Dietéticos , Femenino , Helmintiasis/epidemiología , Helmintiasis/etnología , Helmintiasis/fisiopatología , Hemoglobinopatías/epidemiología , Hemoglobinopatías/etnología , Hemoglobinopatías/fisiopatología , Humanos , Lactante , Hierro de la Dieta/administración & dosificación , Hierro de la Dieta/uso terapéutico , Malaria/epidemiología , Malaria/etnología , Malaria/fisiopatología , Masculino , Embarazo , PrevalenciaRESUMEN
Evidence suggests that relaxin-3 may have biological functions in the reproductive and central nervous systems. To date, however, relaxin-3 biodistribution has only been investigated in the mouse, rat, pig and teleost fish. Characterizing relaxin-3 gene structure, expression patterns, and function in non-human primates and humans is critical to delineating its biological significance. Experiments were performed to clone the rhesus macaque orthologues of the relaxin-3 peptide hormone and its cognitive receptors (RXFP1 and RXFP4). An investigation of rhesus relaxin-3 bioactivity and RXFP1 binding properties was also performed. Next we sought to investigate relaxin-3 immunoreactivity in human and rhesus macaque tissues. Immunohistofluorescence staining for relaxin-3 in the brain, testis, and prostate indicated predominant immunostaining in the ventral and dorsal tegmental nuclei, interstitial space surrounding the seminiferous tubules, and prostatic stromal cells, respectively. Further, in studies designed towards exploring biological functions, we observed neuroprotective actions of rhesus relaxin-3 on human neuronal cell cultures. Taken together, this study broadens the significance of relaxin-3 as a peptide involved in both neuronal cell function and reproductive tissues in primates.