Asunto(s)
Diagnóstico por Imagen/métodos , Diagnóstico por Imagen/tendencias , Eficiencia , Registros Electrónicos de Salud , Seguridad del Paciente , Servicio de Radiología en Hospital , Flujo de Trabajo , Análisis Costo-Beneficio , Diagnóstico por Imagen/economía , Humanos , Centros de Atención Terciaria , Factores de Tiempo , Listas de EsperaRESUMEN
AIMS AND OBJECTIVES: Varicocele embolization is a growing treatment modality owing to the safety, efficacy, and quick return to work following the procedure. The internet is the most dominant source of information for many. We aimed to assess the quality of information accessible by patients considering treatment. MATERIALS AND METHODS: A list of applicable, commonly used searchable terms was generated. Each term was assessed across the five most-used English language search engines to determine the two most commonly used terms. These two terms were then investigated across each search engine, with the first 25 web pages returned by each engine included for analysis. Duplicate web pages, nontext content such as video or audio, and web pages behind paywalls were excluded. Web pages were analyzed for quality and readability using validated tools including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary features including age, rank, author, and publisher were recorded. RESULTS: The most common applicable terms were "Testicular embolization" (378,300 results) and "Varicocele embolization" (375,800 results). Mean DISCERN quality of information provided by websites is "fair"; Adherence to JAMA Benchmark Criteria was 13.5%. Flesh-Kincaid readability tests demonstrated an average "9th grade" reading level. Scientific journals showed the highest quality scores, but were least up to date with an average web page age of 11.2 years. Web pages produced by "for-profit" organizations were the second most current (average age 2.7 years), but displayed the lowest quality of information scores. CONCLUSION: While quality of online information available to patients is "fair," adherence to JAMA benchmark criteria is poor. "For-profit" organization websites are far more numerous and significantly more up-to-date, yet showed significantly lower quality of information scores. Scientific journals were unsurprisingly of higher quality, yet more challenging for the general public to read. These findings call for the production of high-quality and comprehensible content regarding interventional radiology, where physicians can reliably direct their patients for information.
Asunto(s)
Embolización Terapéutica , Varicocele , Preescolar , Comprensión , Humanos , Internet , Masculino , Lectura , Motor de Búsqueda , Varicocele/diagnóstico por imagen , Varicocele/terapiaRESUMEN
Idiopathic intracranial hypertension (IIH) is positively associated with obesity, mostly in young women. The global increase in obesity may influence the burden of IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta-analysis and systematic review of epidemiological studies of IIH were performed up to June 2017. Temporal changes in IIH incidence were measured, and incidence rates of IIH were correlated with country-specific World Health Organization obesity rates. Prevalence data and shunting rates of IIH were recorded. The quality of epidemiological studies was assessed using the Standards of Reporting of Neurological Disorders (STROND) criteria. In 15 identified studies, there were 889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from 0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100 000 per year although there was very high heterogeneity (I2 98%). The incidence rates of IIH were correlated with country-specific prevalence of obesity (Spearman's correlation 0.82, P < 0.01). The prevalence of IIH was rarely recorded. A shunting procedure was reported in 8% of patients. STROND criteria were variably reported, median of 26.5 of 43 (range 16-35). IIH is a public health concern as increased obesity prevalence is associated with increased incidence of IIH. A better quality of epidemiological studies is required to improve understanding of IIH and inform health policy for IIH management.
Asunto(s)
Obesidad/epidemiología , Seudotumor Cerebral/epidemiología , Adulto , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study is to assess the applicability of standard adult carpal angle measurements, specifically the scapholunate and capitolunate angles, in the assessment of the pediatric wrist. MATERIALS AND METHODS: The study cohort comprised male and female children who underwent a wrist radiograph for the evaluation of suspected wrist injuries following trauma. A gender- and indication-matched adult cohort was also assessed. To ensure an accurate carpal angle measurement, only individuals with a sufficiently ossified carpus and an adequately positioned lateral wrist radiograph were included. RESULTS: Carpal angle measurements were performed on the lateral wrist radiographs of 256 individuals between the ages of 5 and 17 years (mean 11.2 years, SD ± 2.5 years) and 256 individuals between the ages of 18 and 40 years (mean 28.8 years, SD ± 6.2 years). The mean pediatric scapholunate angle was 47° (SD ± 8) and the mean pediatric capitolunate angle was 11° (SD ± 7). The mean adult scapholunate and capitolunate angles were 48° (SD ± 8°) and 10° (SD ± 6°) respectively. No statistically significant difference was observed between the scapholunate or capitolunate angle measurements in the two groups (p = 0.26 and p = 0.36). CONCLUSION: The study data supports the applicability of standard adult carpal angle values to the pediatric population provided the carpus is sufficiently ossified.
Asunto(s)
Articulaciones del Carpo/diagnóstico por imagen , Traumatismos de la Muñeca/diagnóstico por imagen , Adolescente , Adulto , Hueso Grande del Carpo/diagnóstico por imagen , Huesos del Carpo , Articulaciones del Carpo/anatomía & histología , Niño , Preescolar , Femenino , Humanos , Inestabilidad de la Articulación , Hueso Semilunar/diagnóstico por imagen , Masculino , Radiografía , Estudios Retrospectivos , Hueso Escafoides/diagnóstico por imagen , Articulación de la Muñeca/diagnóstico por imagen , Adulto JovenRESUMEN
PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation in the prostate epithelium promotes both epithelial-mesenchymal transition (EMT) and metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically defined cellular and in vivo model systems from which epithelial, EMT and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial-mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and markedly reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589.
Asunto(s)
Transición Epitelial-Mesenquimal/efectos de los fármacos , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Animales , Western Blotting , Línea Celular Tumoral , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Masculino , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Ratones Transgénicos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Panobinostat , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacosRESUMEN
The planet Mars hosts an atmosphere that is perhaps the closest in terms of its meteorology and climate to that of the Earth. But Mars differs from Earth in its greater distance from the Sun, its smaller size, its lack of liquid oceans and its thinner atmosphere, composed mainly of CO(2). These factors give Mars a rather different climate to that of the Earth. In this article we review various aspects of the martian climate system from a physicist's viewpoint, focusing on the processes that control the martian environment and comparing these with corresponding processes on Earth. These include the radiative and thermodynamical processes that determine the surface temperature and vertical structure of the atmosphere, the fluid dynamics of its atmospheric motions, and the key cycles of mineral dust and volatile transport. In many ways, the climate of Mars is as complicated and diverse as that of the Earth, with complex nonlinear feedbacks that affect its response to variations in external forcing. Recent work has shown that the martian climate is anything but static, but is almost certainly in a continual state of transient response to slowly varying insolation associated with cyclic variations in its orbit and rotation. We conclude with a discussion of the physical processes underlying these long- term climate variations on Mars, and an overview of some of the most intriguing outstanding problems that should be a focus for future observational and theoretical studies.
RESUMEN
A significant amount of valuable undergraduate medical teaching may be informal, unscheduled and delivered by non-consultant hospital doctors (NCHDs). 800 Questionnaires were distributed to consultants, NCHDs and medical students in Irish teaching hospitals. The aim was to quantify the level of unscheduled teaching carried out in these hospitals and the manner in which it was performed. The response rate was 46% (364/800). 71% of doctors who replied are independently teaching undergraduate medical students (77/109), including 71% of interns and senior house officers (48/68). Students tend to prefer small group teaching. Fifty-six percent of students suggest they would benefit from more surgical teaching time (144/255). No interns surveyed were scheduled to teach as part of a formal curriculum. A significant amount of unscheduled teaching by interns and senior house officers takes place in Irish hospitals. It may prove beneficial to incorporate interns into scheduled surgical teaching curricula.
Asunto(s)
Actitud del Personal de Salud , Educación de Pregrado en Medicina , Cirugía General/educación , Enseñanza , Curriculum , Educación de Pregrado en Medicina/métodos , Educación de Pregrado en Medicina/organización & administración , Hospitales de Enseñanza , Humanos , Irlanda , Cuerpo Médico de Hospitales/psicología , Evaluación de Necesidades , Estudiantes de Medicina/psicología , Encuestas y CuestionariosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Khaya species, endemic to Africa and Madagascar, continues to be valuable in indigenous traditional medicine. Their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. In the Budongo rain forest of Western Uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed. MATERIALS AND METHODS: Extracts were prepared by sequential fractionation with solvents of increasing polarities and assayed using standard procedures. Bioassay guided purification of the petroleum ether extract by column chromatography yielded three pure limonoids, Grandifolione (1), 7-deacetylkhivorin (2) and 1,3-deacetyldeoxyhavenensin (3). The antitrypanosomal, antileishmanial and antiplasmodial activities of pure compounds (1) and (2) were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi trypomastigotes (Tulahuen C4), and axenic Leishmania donovani MHOMET-67/L82 and for cytotoxicity against L6 rat skeletal myoblast cells, in parallel with standard drugs. RESULTS: Of the four extracts tested, the petroleum ether extract showed activity against Plasmodium falciparum (IC50 0.955 µg/ml) and Trypanosoma brucei rhodesiense (IC50 5.72 µg/ml). The pure compounds (1) and (2) demonstrated activity against Plasmodium falciparum (KI strain) and marginal activities against Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. CONCLUSION: The present study provides evidence justifying the use of Khaya preparations in traditional medicine to treat fevers and microbial infections. The observed antiprotozoal activity of grandifolione and 7-deacetylkhivorin from the seed of Khaya anthotheca further confirms the ethnomedicinal potential of this plant and supports the hypothesis that non-human hominids (chimpanzees and baboons) too, eat the bitter bark and seeds for self-medication and in general, the use of Khaya plant material for medication by humans in disease endemic tropical areas. The antiprotozoal activity of gradifolione, and, the antitrypanosomal and antileishmanial activities of 7-deacetylkhivorin are reported here for the first time.
Asunto(s)
Antiprotozoarios/farmacología , Conducta Animal , Meliaceae , Pan troglodytes , Animales , Antimaláricos/farmacología , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/toxicidad , Bioensayo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fraccionamiento Químico , Cromatografía , Concentración 50 Inhibidora , Leishmania donovani/efectos de los fármacos , Meliaceae/química , Mioblastos Esqueléticos/efectos de los fármacos , Mioblastos Esqueléticos/patología , Pruebas de Sensibilidad Parasitaria , Fitoterapia , Corteza de la Planta , Plantas Medicinales , Plasmodium falciparum/efectos de los fármacos , Ratas , Semillas , Solventes/química , Tripanocidas/farmacología , Trypanosoma brucei rhodesiense/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Duplication of the gallbladder is a surprisingly common phenomenon. Clinically, these patients present with straightforward gallbladder pathologies. It is a challenging preoperative diagnosis on ultrasound, and most cases are diagnosed intra-operatively. We present a case of gallbladder duplication, where the patient presented with biliary colic, had a straightforward laparoscopic cholecystectomy, and then represented with biliary colic four years later.
Asunto(s)
Colecistectomía Laparoscópica , Vesícula Biliar/anomalías , Pancreatocolangiografía por Resonancia Magnética , Colecistolitiasis/diagnóstico por imagen , Femenino , Vesícula Biliar/diagnóstico por imagen , Humanos , Reoperación , Ultrasonografía , Adulto JovenRESUMEN
We studied the outcomes of seventeen patients treated surgically for extratemporal lobe epilepsy. A retrospective case review of medical charts was performed. Seizure freedom post surgery was appraised using the Engel classification system. Post-operatively seven patients (41%) were seizure free (Engel class I), four patients were class II (23.5%), two in class III (11.76%) and four in class IV (23.5%). Three patients (17.6%) suffered traumatic injuries due to seizures. The mean duration of epilepsy prior to surgery was 12.2 years and the mean number of anti-epileptic medications given was 6.5. Seizure freedom rates for surgical treatment of extratemporal epilepsy in this centre are similar to those of other centres. Post-operative morbidity in this centre was similar to other centres. Any complications resolved with no lasting impairment.
Asunto(s)
Epilepsias Parciales/cirugía , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Preescolar , Epilepsias Parciales/tratamiento farmacológico , Femenino , Humanos , Masculino , Procedimientos Neuroquirúrgicos , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Regression analyses of local medicinal floras are considered potentially useful when prioritising candidate plant taxa for pharmacological/bioprospecting investigations. AIM OF THE STUDY: To identify plant orders and subsequently families within the highly diverse ethnomedicinal flora of southern Africa, towards which biases by traditional healers are demonstrable. Taxa so identified can subsequently be weighted appropriately in semi-quantitative selection systems. METHODOLOGY: Plant data sourced from the SANBI MedList database, the most comprehensive inventory of ethnomedicinal plants for the Flora of southern Africa region were grouped by order. A least squares regression analysis was applied to test the null hypothesis that the use of these plants by traditional healers is strictly random. Of 'hot' orders subsequently identified, characteristics of taxa therein were assessed to better determine the roles played by (i) growth forms, and (ii) inherent chemical diversity, in plant selections by ethnomedicinal practitioners. RESULTS: Analyses identified seven principally 'hot' plant orders (Malpigiales, Fabales, Gentianales, Asteraceae, Solanales, Malvales and Sapindales) and 'hot' families therein from a total of 55 regional ethnomedicinal orders. Five 'cold' ethnomedicinal orders (Rosales, Proteales, Poales, Asparagales and Caryophyllales) were shown to be significantly less represented in the medicinal flora than predicted. No clear growth form preferences were identified across orders. The presence of highly diverse bioactives was evident in the 'hottest' plant families from 'hot' plant orders. CONCLUSIONS: These 12 outliers identified by the regression analyses allowed for the falsification of the null hypothesis. Indications are that 'hot' taxa are selected traditionally on the basis of bioactivity, which is reflected in chemical diversity.
Asunto(s)
Evaluación Preclínica de Medicamentos/estadística & datos numéricos , Medicinas Tradicionales Africanas , Plantas Medicinales/clasificación , África Austral , Animales , Bases de Datos Factuales , Humanos , Análisis de los Mínimos Cuadrados , Modelos Estadísticos , Plantas Medicinales/química , Análisis de Regresión , SudáfricaRESUMEN
Hermannia species are widely used in traditional medicine in southern Africa, however no extensive study has been conducted on this genus. The acetone extracts of 12 indigenous Hermannia species (flowers, stems and leaves combined) were evaluated for various pharmacological activities. All investigated species displayed promising antimicrobial activity, with Hermannia saccifera being the most active against Staphylococcus aureus (MIC=19.5 microg/ml), Bacillus cereus (MIC=19.5 microg/ml) and Enterococcus faecalis (MIC=125 microg/ml). Time-kill studies on H. saccifera against S. aureus indicated bacteriostatic activity at 1.25, 2.5 and 5.0%, and a concentration of 7.5% achieved complete bactericidal activity after 4h. Ten of the 12 species indicated good free radical scavenging activity, with H. cuneifolia demonstrating the most promising activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH():IC(50)=10.26 microg/ml) and 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)/TEAC: IC(50)=10.32 microg/ml) assays. In addition, all species exhibited moderate anti-inflammatory activity in the 5-lipoxygenase assay with the exception of H. cuneifolia (IC(50)=15.32 microg/ml). Overall, the selected species were low in cytotoxicity, except for H. saccifera and H. trifurca. Several Hermannia species indicated promising in vitro biological activity which relate to their traditional use in treating a number of disease states.
Asunto(s)
Malvaceae/química , Fitoterapia , Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Benzotiazoles , Compuestos de Bifenilo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Hongos/efectos de los fármacos , Humanos , Cinética , Inhibidores de la Lipooxigenasa , Malvaceae/clasificación , Medicinas Tradicionales Africanas , Pruebas de Sensibilidad Microbiana , Picratos , Extractos Vegetales/farmacología , Solventes , Sudáfrica , Ácidos SulfónicosRESUMEN
Years ago we undertook to define Health Informatics (HI) competencies. This effort resulted in the creation of a document that articulated HI roles, the challenges faced by HI professionals, the high-level tasks that they needed to undertake to address these challenges and the competencies (skills, knowledge, and experience) they needed to complete these tasks. Unfortunately, in so doing we created what is arguably the most boring book in history, shoes contents are very difficult to extract, use, maintain and improve. We report here the completion of a pilot of a system that we believe corrects this situation. It is a webbased tool that incorporates all of the material, from roles to detailed competencies, enabling them to be accessed and used for a variety of purposes, the most notable of which is professional self-assessment.
Asunto(s)
Alfabetización Digital , Evaluación Educacional/métodos , Informática/educación , Autoevaluación (Psicología) , Bases de Datos como Asunto , Humanos , Internet , Proyectos Piloto , Competencia ProfesionalRESUMEN
In this analysis, employing 2002 data from SLAN Survey of Lifestyles, Attitudes and Nutrition and mortality data from the Eastern region of the Republic of Ireland, we examined predictors of area level variability in self-rated health across 101 electoral divisions (ED)s. Overall 11.5% of 1500 participants reported fair or poor health. We found area level variation in poor self-rated health (0.0357 (SE 0.160), p = 0.03), which was related significantly to area-level standardised mortality ratio. Odds of poor self-rated health, adjusted for age and sex were 1.55 (95% CI 0.89, 2.71) in average SMR areas and 2.61 (95% CI 1.38, 4.92) in high SMR areas compared to low SMR areas. Adjusted models for age, sex, general medical services eligibility, an established proxy for income, problems in the neighbourhood and smoking rates largely explained any variability, suggesting a strong role for individual disadvantage in predicting health status, regardless of area, in Ireland.
Asunto(s)
Actitud Frente a la Salud , Estado de Salud , Pobreza , Calidad de Vida , Poblaciones Vulnerables/psicología , Factores de Edad , Estudios Transversales , Femenino , Geografía , Encuestas Epidemiológicas , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Factores Sexuales , Análisis de Área Pequeña , Encuestas y CuestionariosRESUMEN
The stem bark of Zanthoxylum rubescens (syn. Fagara rubescens) is used for treating fevers associated with malaria in the Ivory Coast. Three alkaloids: N-nornitidine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, and bis[6-5,6-dihydrochelerythrinyl)] ether; and two amides: zanthomamide and lemairamide, were isolated from the stem bark of this plant. These compounds were screened in vitro against the chloroquine-sensitive 3D7 strain and the chloroquine-resistant FCM29 strain of P. falciparum. N-nornitidine was found to be inactive. 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, lemairamide and zanthomamide showed weak activity with average IC50 values ranging from 45.6 microM to 149.9 microM. Bis[6-15,6-dihydrochelerythrinyl)] ether was the most active of the tested compounds with mean IC50s of 14.9 +/- 1.4 microM in FCM29 strain and 15.3 +/- 3.4 microM in 3D7 strain (approximately 58 to approximately 1130 times less active than chloroquine respectively). The anti-Plasmodium activities of the tested alkaloids of Z. rubescens were low; and do not encourage the use of this plant as antimalarial.
Asunto(s)
Antimaláricos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plasmodium falciparum/efectos de los fármacos , Zanthoxylum/química , Alcaloides/aislamiento & purificación , Alcaloides/uso terapéutico , Amidas/aislamiento & purificación , Amidas/uso terapéutico , Animales , Cloroquina/uso terapéutico , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Resultado del TratamientoRESUMEN
Oleanolic acid, scoparone, scopoletin and a novel iridoid derivative, angelone, were isolated from Tachiadenus longiflorus (Gentianaceae). The structure of angelone was determined from NMR data, given as input to the Logic for Structure Determination Programme, and was finally confirmed by comparison of experimental 13C-NMR chemical shifts with those obtained by quantum mechanical calculations.
Asunto(s)
Gentianaceae/química , Iridoides/química , Pironas/química , Programas Informáticos , Estructura Molecular , Corteza de la Planta/química , Tallos de la Planta/químicaRESUMEN
Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.
Asunto(s)
Antimutagênicos/farmacología , Mutágenos/farmacología , Extractos Vegetales/química , Plantas/química , Salmonella typhimurium/efectos de los fármacos , Datura stramonium/química , Helichrysum/química , Medicinas Tradicionales Africanas , Metanol/metabolismo , Cloruro de Metileno/metabolismo , Pruebas de Mutagenicidad , Salmonella typhimurium/crecimiento & desarrollo , SudáfricaRESUMEN
Prostate cancer (PrCa) is characterized by progression from an androgen-dependent phenotype to one that is inevitably androgen independent (AI) and lethal. Recent evidence strongly suggests that the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) and androgen receptor (AR) signalling pathways provide prostatic epithelium with the necessary signalling events to escape the apoptotic response associated with androgen withdrawal therapy. Silencing of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and glycogen synthase kinase beta (GSK3beta) are frequently associated with advanced PrCa systems and likely serve critical roles in promoting AR and PI3K/Akt gain-of-function. That PTEN negatively regulates AR and is sufficient to promote metastatic PrCa in murine models strongly implies its role as a gatekeeper of progressive PrCa. In human PrCa, PTEN loss is correlated with substantial increases in Akt(Ser473) and integrin-linked kinase expression, both of which promote Ser(9) phospho-inhibition of GSK3beta and inactivation of apoptotic factors. Sufficient evidence also suggests that GSK3beta is not only a critical regulator of proproliferative signalling but also a promiscuous one as PI3K/Akt pools of GSK3beta are, at least in part, functionally interchangeable with those of the Wnt/beta-catenin pathway. Thus, GSK3beta may serve not only as a mediator of PI3K/Akt activation but may also regulate the potent transactivation and proproliferative effects that Wnt3a and beta-catenin confer upon AR. These data suggest that prostate-specific activation of GSK3beta may serve as a viable pharmacological option. Thus, in this review, we emphasize that temporal changes in GSK3beta and PTEN expression during progression to AI PrCa are important factors when considering the potential for therapies targeting the oncogenic contributions of PI3K/Akt and AR signalling pathways.