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Infantile haemangiomas (IHs) with functional or cosmetic concerns necessitate systemic treatment for which propranolol is the preferred treatment. However, the mechanism of action is unknown. Mouse models suggest the angiopoietin-2 (Ang2)/Tie-2 system is implicated. Ang2 can promote endothelial growth or induce apoptosis depending on the presence of vascular endothelial growth factor. This pilot study investigates the saliva Ang2 levels in infants with IH treated with and without systemic propranolol. Patients with clinically confirmed IHs were recruited from an academic paediatric dermatology centre. Treatment was based on clinical evaluation. Saliva samples were collected over 6 months. An enzyme-linked immunosorbent assay determined Ang2 levels. Ang2 levels were detectable in 45% of samples. However, by the late time point, only 28% had detectable levels. There were no changes of Ang2 over time, and there were no differences in Ang2 levels between groups. However, Ang2 levels were correlated with baseline size and changes in size from baseline. Ang2 is detectable in saliva of affected infants, but does not decrease with propranolol treatment. However, Ang2 levels are positively correlated with size and changes in size. Thus, Ang2 is not the primary factor in the mechanism of propranolol resulting in IH reduction.
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Angiopoyetina 2/metabolismo , Hemangioma Capilar/tratamiento farmacológico , Hemangioma Capilar/metabolismo , Síndromes Neoplásicos Hereditarios/tratamiento farmacológico , Síndromes Neoplásicos Hereditarios/metabolismo , Propranolol/uso terapéutico , Saliva/metabolismo , Vasodilatadores/uso terapéutico , Femenino , Hemangioma Capilar/patología , Humanos , Lactante , Masculino , Síndromes Neoplásicos Hereditarios/patología , Proyectos Piloto , Factores de TiempoRESUMEN
Unique iodine-containing meroditerpenes iodocallophycoic acid A (1) and iodocallophycols A-D (2-5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 µg mL-1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 µg mL-1.
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Diterpenos/análisis , Yodo/química , Rhodophyta/química , Diterpenos/química , Diterpenos/farmacología , Enterococcus faecium/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Teóricos , Análisis Espectral/métodos , EstereoisomerismoRESUMEN
BACKGROUND: Plant material from different organs of Pistacia terebinthus L., (Anacardiaceae) were collected in Kosovo with aim to analyze the chemical variability of the essential oils among native populations and to test them for potential antibacterial activity against Staphylococcus aureus. METHODS: Essential oils obtained from leaves, pedicels, fruits and galls were analyzed by GC-FID and GC/MS. Minimum inhibitory concentration (MIC) against three clinically relevant strains of S. aureus (NRS385, LAC and UAMS-1) were used to evaluate the antibacterial activity of essential oils. RESULTS: In total, 33 different compounds were identified. The main constituents were α-pinene (12.58-66.29 %), D-limonene (13.95-46.29 %), ß-ocimene (0.03-40.49 %), ß-pinene (2.63-20.47 %), sabinene (0.00-5.61 %) and (Z)-ß-ocimene (0.00-44.85 %). Antibacterial testing of the essential oils against three clinical isolates of S. aureus revealed that seven of the eight samples had some activity at the concentration range tested (0.04-0.512 % v/v). The gall tissues from both sites produced the highest yield of essential oil (3.24 and 6 %), and both exhibited growth inhibitory activity against S. aureus. The most bioactive essential oils, which exhibited MIC90 values ranging from 0.032-0.128 % v/v, obtained from the fruits of the Ura e Shejtë collection site. Likewise, the leaf and pedicel essential oil from the same site was highly active with MIC90 values of 0.064-0.128 and 0.032-0.256 % v/v, respectively. CONCLUSIONS: Principle Component Analyses demonstrated that there is a variation in the chemical composition of essential oil depending on the plant organs from which essential oil are obtained and the geographical origin of the plant populations. The highest variability regarding the chemical composition of essential oil was found between oils obtained from different organs originating from the Prizren site. The MIC90 activity of Pistacia terebinthus was on par or superior compared with Tea Tree Oil control (0.128 % v/v), suggesting that essential oils from this species may have some potential for development as an antibacterial agent for S. aureus infections.
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Antibacterianos/farmacología , Aceites Volátiles/farmacología , Pistacia/química , Aceites de Plantas/farmacología , Antibacterianos/química , Kosovo , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/química , Aceites de Plantas/química , Análisis de Componente Principal , Staphylococcus aureus/efectos de los fármacosRESUMEN
OBJECTIVE: Decision-making about antireflux procedures (ARPs) to treat gastroesophageal reflux disease in children with neurologic impairment and gastrostomy tubes is challenging and likely influenced by physicians' experience and perspectives. This study will explore physician attitudes about ARPs and determine if there are relationships to clinical practice and personal characteristics. METHODS: This is a national observational cross-sectional study that used an electronic questionnaire addressing reported practice, attitudes regarding the ARPs, and responses to clinical vignettes. Participants were physicians in Canadian tertiary-care pediatric settings. Descriptive statistics were used to analyze physician attitudes. Multivariable logistic regression modeling was used to determine associations between physician and practice characteristics and likelihood to consider ARP. RESULTS: Eighty three respondents represented 12 institutions, with a majority from general or complex care pediatrics. There was a wide disparity between likelihood to consider ARP in each clinical scenario. Likelihood to consider ARP ranged from to 19% to 78% depending on the scenario. Two scenarios were equally split in whether the respondent would offer an ARP. None of the demographic characteristics were significantly associated with likelihood to consider ARP. Often, gastrojejunostomy tubes alone were considered (56% to 68%). CONCLUSIONS: There is considerable variability in physician attitudes toward and recommendations regarding ARPs to treat gastroesophageal reflux disease. We did not find a significant association with clinical experience or location of practice. More research is needed to define indications and outcomes for ARPs. This is a scenario where shared decision-making, bringing together physician and family knowledge and expertise, is likely the best course of action.
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Actitud del Personal de Salud , Reflujo Gastroesofágico , Pautas de la Práctica en Medicina , Humanos , Reflujo Gastroesofágico/terapia , Estudios Transversales , Canadá , Masculino , Femenino , Pautas de la Práctica en Medicina/estadística & datos numéricos , Niño , Enfermedades del Sistema Nervioso/terapia , Encuestas y Cuestionarios , Gastrostomía , Toma de Decisiones Clínicas , Fundoplicación , AdultoRESUMEN
BACKGROUND: There is growing global concern about poor mental health among adolescents in sub-Saharan Africa. In particular, adolescent girls face multiple challenges in managing menstruation which can impact both their health and wellbeing. In this study we address an evidence gap on the association of a broad range of menstrual-related factors with mental health problems amongst secondary school female adolescents in Uganda. METHODS: We used baseline data from a cluster-randomised menstrual health intervention trial conducted in 60 secondary schools in two districts in Uganda. Baseline data were collected between March and July 2022, including socio-demographic characteristics, menstrual knowledge and attitudes, menstrual practices and self-efficacy, and mental health problems measured using the Strengths and Difficulties Questionnaire Total Difficulties score (SDQ-25). We used random-effects linear regression to estimate the adjusted mean difference (aMD) for the association between mental health problems (SDQ Total Difficulties Score) and menstrual-related factors, including the Menstrual Practice Needs Scale (MPNS) and the Self-Efficacy in Addressing Menstrual Needs scale (SAMNS)), accounting for school-level clustering and adjusting for prior confounders. RESULTS: Among the 3841 female participants, there was strong and consistent evidence of associations between mental health problems and menstrual-related factors. Mental health problems were associated with poor knowledge about menstruation (aMD = 1.17, 95%CI 0.50, 1.84 <0.001), using disposable and reusable menstrual products compared to using just disposable products (aMD = 1.42, 95%CI 0.92, 1.92, p <0.001), and experiencing menstrual pain even when using an effective management method at last menstrual period (LMP) compared to those experiencing no pain (aMD = 1.60, 95%CI 1.19, 2.01, p <0.001). Mental health problems were also associated with greater unmet menstrual needs according to the MPNS (aMD = 4.40 95%CI 3.96, 4.84, p <0.001), and with lower menstrual self-efficacy measured by the SAMNS (aMD = 0.94 95% CI 0.51, 1.37, p <0.001). CONCLUSION: This study shows strong evidence that mental health problems reported by adolescent girls in Uganda are associated with poor menstrual health. The association between menstrual health and mental health provides evidence as to why menstrual health should be a public health priority. TRIAL REGISTRATION: Trial registration: ISRCTN 45461276. Registered on 16 September 2021.
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The DREAMS partnership aims to deliver a comprehensive package to reduce HIV incidence among adolescent girls and young women (AGYW), including through shifting gender norms. We evaluate DREAMS' effect on attitudes towards gender norms in two Kenyan settings. AGYW aged 15-22 in Nairobi (n = 852) and Gem (n = 761) were randomly selected for cohort enrolment in 2017-18 and followed-up to 2019. We described the proportion of AGYW and their male peers with equitable attitudes towards gender norms, using an adapted version of the GEM scale. We estimated the association between self-reported invitation to DREAMS (in 2017-18) and AGYW's attitudes towards two dimensions of gender norms, and then applied a causal inference framework to estimate the difference in the proportion of AGYW with equitable attitudes under the counterfactual scenarios that all versus none were DREAMS beneficiaries. We estimated that overall, 90.2% versus 87.1% of AGYW would have equitable norms around sexual and reproductive health decision-making in Nairobi if all versus none were DREAMS beneficiaries (+3.1; 95%CI:-2.5, +9.0). In Gem, we estimated a risk difference of +1.0 (89.6% vs 88.6%, 95%CI: -3.6,+5.6). There was no evidence for an effect of DREAMS on attitudes towards violence-related norms (Nairobi: 82.7% vs 82.2%, +0.5; 95%CI: -5.3,+6.5; Gem: 44.3% vs 48.2%, -3.9; 95%CI: -11.7,+3.0). We found no evidence of an impact of DREAMS invitation on individual attitudes towards gender norms. In some cases, equitable attitudes at enrolment left limited scope for improvement, and additional effort may be required to shift inequitable violence attitudes among both AGYW and their male peers.
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BACKGROUND: Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling. Development of animal models amenable to longitudinal examination enables distinct disease-associated mechanisms to be identified. RESULTS: Here we report the first longitudinal study of transgenic monkeys with genomic integration of various lengths of the human HTT gene and a range of polyQ repeats. With this unique group of transgenic HD nonhuman primates (HD monkeys), we profiled over 47,000 transcripts from peripheral blood collected over a 2 year timespan from HD monkeys and age-matched wild-type control monkeys. CONCLUSIONS: Messenger RNAs with expression patterns which diverged with disease progression in the HD monkeys considerably facilitated our search for transcripts with diagnostic or therapeutic potential in the blood of human HD patients, opening up a new avenue for clinical investigation.
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Enfermedad de Huntington/genética , Proteínas del Tejido Nervioso/genética , Transcriptoma , Animales , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Proteína Huntingtina , Enfermedad de Huntington/sangre , Estudios Longitudinales , Macaca mulatta , Masculino , ARN Mensajero/metabolismoRESUMEN
Adolescent girls face social, psychological, and physical problems managing menstruation in schools in low-resource settings. This study aimed to evaluate the social and physical menstrual health environment of secondary schools in Wakiso and Kalungu districts, Uganda, in preparation for a subsequent menstrual health intervention trial to improve education, health and wellbeing. We conducted a qualitative rapid assessment in 75 secondary schools in Uganda. This involved conducting in-depth interviews with 150 head/senior teachers and 274 students, 26 Focus Group Discussions with students, and 13 transect walks to observe school Water, Sanitation and Hygiene (WASH) facilities between May and October 2021. Due to COVID-19 related school closures, face-to-face research activities were halted and in-depth interviews were conducted over phone and replaced focus group discussions. We employed a thematic framework analysis approach using the social-ecological model (which focuses on the complex interplay between individual, interpersonal, institutional, and societal factors) to generate themes and key concepts. Participants described the social and physical menstrual health environment of secondary schools at the individual level (knowledge gaps on menstruation before menarche, negative norms and beliefs about menstrual health); interpersonal level (limited psycho-social support, myths and misconceptions about the disposal of sanitary materials and pain relief, menstrual hygiene management (MHM) support from school nurses, peers and senior teachers); institutional level (non-implementation of Government circulars on MHM, lack of school-level guidelines policies and programs on MHM and poor WASH facilities, i.e. lack of soap, safe water and unclean toilets); and societal level (MHM programmes provided by civil society groups, health workers, and students' school associations). The findings showed individual, societal and institutional burdens related to menstrual experiences. Multi-level evidence-based interventions aimed at improving the social and physical environment for menstrual health among school-going girls are needed.
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BACKGROUND: Anthracycline and taxane-based doublets have largely replaced cyclophosphamide, methotrexate, and fluorouracil (CMF) as preferred regimens in the adjuvant treatment of breast cancer. Metronomic CMF is associated with improved tolerability over anthracycline or taxane-based regimens. Previously, there have been no direct comparisons between taxane-based regimens and CMF. MATERIALS AND METHODS: We performed a retrospective review of 98 breast cancer patients treated at the Seattle Cancer Care Alliance from February 2015 through December 2018 that received either metronomic CMF or docetaxel and cyclophosphamide (TC) as adjuvant therapy for early-stage, hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) breast cancer. The primary outcome assessed was disease-free survival (DFS). Secondary outcomes included overall survival (OS), dose intensity, and adverse effects. RESULTS: With an average follow-up of 35.9 and 28.2 months for CMF and TC, respectively, there was no significant difference in DFS or OS between the chemotherapy regimens. DFS at 3 years was 96.7% vs. 94.3% and OS 96.7% vs. 100% for CMF and TC, respectively. There were more dose delays in the CMF group, but on average, patients receiving either regimen achieved a dose intensity ≥85%. There was a trend towards increased hospitalization or emergency department utilization (23.1% vs. 10.6%) and Grade 4 toxicities (9.6% vs. 4.3%) with TC vs. CMF. CONCLUSION: Metronomic CMF offers equivalent survival outcomes to TC and remains a viable option in the adjuvant treatment of HR+/HER2- breast cancer. There was a trend towards increased Grade 4 toxicities and hospitalizations with TC, suggesting that metronomic CMF may offer a more tolerable treatment option while maintaining excellent disease outcomes.
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Neoplasias de la Mama , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Ciclofosfamida , Docetaxel/uso terapéutico , Femenino , Fluorouracilo , Humanos , Metotrexato , Estudios Retrospectivos , Taxoides/uso terapéuticoRESUMEN
BACKGROUND: Menstrual health is an increasingly recognised public health issue, defined as complete physical, mental, and social well-being in relation to the menstrual cycle. The MENISCUS trial aims to assess whether a multi-component intervention addressing physical and emotional aspects of menstrual health improves educational attainment, mental health problems, menstrual management, self-efficacy, and quality of life among girls in secondary school in Uganda. METHODS: The study is a parallel-arm cluster-randomised controlled trial with 60 schools (clusters) in Wakiso and Kalungu districts, with a mixed-methods process evaluation to assess intervention fidelity and acceptability and economic and policy analyses. The schools will be randomised 1:1 to immediate intervention or to optimised usual care with delayed intervention delivery. The intervention includes creation of a Menstrual Health Action Group at schools and NGO-led training of trainers on puberty education, development of a drama skit, delivery of a menstrual health kit including reusable pads and menstrual cups, access to pain management strategies including analgesics, and basic improvements to school water, sanitation, and hygiene facilities. Baseline data will be collected from secondary 2 students in 2022 (median age ~15.5 years), with endline after 1 year of intervention delivery (~3600 females and a random sample of ~900 males). The primary outcomes assessed in girls are (i) examination performance based on the Mathematics, English, and Biology curriculum taught during the intervention delivery (independently assessed by the Uganda National Examinations Board) and (ii) mental health problems using the Total Difficulties Scale of the Strengths and Difficulties 25-item questionnaire. Secondary outcomes are menstrual knowledge and attitudes in girls and boys and, in girls only, menstrual practices, self-efficacy in managing menstruation, quality of life and happiness, prevalence of urogenital infections, school and class attendance using a self-completed menstrual daily diary, and confidence in maths and science. DISCUSSION: The trial is innovative in evaluating a multi-component school-based menstrual health intervention addressing both physical and emotional aspects of menstrual health and using a "training of trainers" model designed to be sustainable within schools. If found to be cost-effective and acceptable, the intervention will have the potential for national and regional scale-up. TRIAL REGISTRATION: ISRCTN 45461276 . Registered on 16 September 2021.
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Menisco , Menstruación , Adolescente , Femenino , Humanos , Masculino , Menstruación/psicología , Salud Mental , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Instituciones Académicas , Estudiantes/psicología , Uganda/epidemiologíaRESUMEN
INTRODUCTION: COVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever) and rVSV-ZEBOV (Ebola virus disease). METHODS: We conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants' experiences. Interview data were analysed thematically according to seven implementation domains. RESULTS: Participants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities. CONCLUSION: As supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.
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COVID-19 , Vacunas contra el Virus del Ébola , Fiebre Hemorrágica Ebola , Meningitis , Fiebre Amarilla , Adulto , Vacunas contra la COVID-19 , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Programas de Inmunización , SARS-CoV-2 , Fiebre Amarilla/epidemiología , Fiebre Amarilla/prevención & controlRESUMEN
BACKGROUND: The medical tourism market is a rapidly growing sector fueled by increasing health care costs, longer domestic waiting times, economic recession, and cheaper air travel. OBJECTIVES: The authors investigate public opinion on undergoing cosmetic surgery abroad and then explore the information patients are likely to encounter on the Internet when searching for such services. METHODS: A poll of 197 members of the general public was conducted in the United Kingdom. An Internet search including the terms plastic surgery abroad was conducted, and the first 100 relevant sites were reviewed. RESULTS: Of the 197 respondents, 47% had considered having some form of cosmetic surgery. Most (97%) would consider going abroad for their procedure. The Internet was a source of information for 70%. The review of the first 100 sites under "plastic surgery abroad" revealed that most centers were located in Eastern Europe (26%), South America (14%), and the Far East (11%). Exploring the information provided on the Web sites, we found 37% contained no information regarding procedures. Only 10% of sites contained any information about potential complications. Even less frequently mentioned (4%) were details of aftercare or follow-up procedures. CONCLUSIONS: The authors found that the overwhelming majority of respondents considering plastic surgery would also consider seeking cosmetic surgical treatment abroad. The Internet sites that appear most prominently in an online search contained a distinct lack of information for potential patients, particularly with regard to complications and aftercare. There is, therefore, a need for improved public awareness and education about the considerations inherent in medical tourism. The introduction of more stringent regulations for international centers providing such services should also be considered to help safeguard patients.
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Internet , Turismo Médico , Procedimientos de Cirugía Plástica/psicología , Opinión Pública , Viaje , Actitud Frente a la Salud , Recolección de Datos , Costos de la Atención en Salud , Humanos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/psicología , Procedimientos de Cirugía Plástica/economía , Procedimientos de Cirugía Plástica/normas , Reino UnidoRESUMEN
A shortage of conventional medicine during the American Civil War (1861-1865) spurred Confederate physicians to use preparations of native plants as medicines. In 1863, botanist Francis Porcher compiled a book of medicinal plants native to the southern United States, including plants used in Native American traditional medicine. In this study, we consulted Porcher's book and collected samples from three species that were indicated for the formulation of antiseptics: Liriodendron tulipifera, Aralia spinosa, and Quercus alba. Extracts of these species were tested for the ability to inhibit growth in three species of multidrug-resistant pathogenic bacteria associated with wound infections: Staphylococcus aureus, Klebsiella pneumoniae, and Acinetobacter baumannii. Extracts were also tested for biofilm and quorum sensing inhibition against S. aureus. Q. alba extracts inhibited growth in all three species of bacteria (IC50 64, 32, and 32 µg/mL, respectively), and inhibited biofilm formation (IC50 1 µg/mL) in S. aureus. L. tulipifera extracts inhibited biofilm formation (IC50 32 µg/mL) in S. aureus. A. spinosa extracts inhibited biofilm formation (IC50 2 µg/mL) and quorum sensing (IC50 8 µg/mL) in S. aureus. These results support that this selection of plants exhibited some antiseptic properties in the prevention and management of wound infections during the conflict.
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Guerra Civil Norteamericana , Antiinfecciosos Locales/farmacología , Aralia/química , Biopelículas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Medicina de Hierbas/historia , Liriodendron/química , Medicina Militar/historia , Extractos Vegetales/farmacología , Plantas Medicinales/química , Quercus/química , Percepción de Quorum/efectos de los fármacos , Antiinfecciosos Locales/aislamiento & purificación , Antiinfecciosos Locales/toxicidad , Farmacorresistencia Bacteriana Múltiple , Bacterias Grampositivas/fisiología , Historia del Siglo XIX , Humanos , Queratinocitos/efectos de los fármacos , Estructura Molecular , Fitoterapia , Extractos Vegetales/toxicidad , Especificidad de la Especie , Infección de Heridas/tratamiento farmacológicoAsunto(s)
Fenómenos Fisiológicos Nutricionales del Lactante , Fenómenos Fisiologicos Nutricionales Maternos , Probióticos , Lactancia Materna , Candidiasis Vulvovaginal/prevención & control , Cólico/prevención & control , Femenino , Humanos , Hipersensibilidad Inmediata/prevención & control , Sistema Inmunológico/crecimiento & desarrollo , Lactante , Fórmulas Infantiles , Mastitis/prevención & control , EmbarazoRESUMEN
Hypericum perforatum L. (Hypericaceae), or St. John's Wort, is a well-known medicinal herb often associated with the treatment of anxiety and depression. Additionally, an oil macerate (Oleum Hyperici) of its flowering aerial parts is widely used in traditional medicine across the Balkans as a topical wound and ulcer salve. Other studies have shown that Oleum Hyperici reduces both wound size and healing time. Of its active constituents, the naphthodianthrone hypericin and phloroglucinol hyperforin are effective antibacterial compounds against various Gram-positive bacteria. However, hyperforin is unstable with light and heat, and thus should not be present in the light-aged oil macerate. Additionally, hypericin can cause phototoxic skin reactions if ingested or absorbed into the skin. Therefore, the established chemistry presents a paradox for this H. perforatum oil macerate: the hyperforin responsible for the antibacterial bioactivity should degrade in the sunlight as the traditional oil is prepared; alternately, if hypericin is present in established bioactive levels, then the oil macerate should cause photosensitivity, yet none is reported. In this research, various extracts of H. perforatum were compared to traditional oil macerates with regards to chemical composition and antibacterial activity (inhibition of growth, biofilm formation, and quorum sensing) vs. several strains of Staphylococcus aureus in order to better understand this traditional medicine. It was found that four Kosovar-crafted oil macerates were effective at inhibiting biofilm formation (MBIC50 active range of 0.004-0.016% v/v), exhibited moderate inhibition of quorum sensing (QSIC50 active range of 0.064-0.512% v/v), and contained detectable amounts of hyperforin, but not hypericin. Overall, levels of hypericin were much higher in the organic extracts, and these also exhibited more potent growth inhibitory activity. In conclusion, these data confirm that oil macerates employed in traditional treatments of skin infection lack the compound credited with phototoxic reactions in H. perforatum use and exhibit anti-biofilm and modest quorum quenching effects, rather than growth inhibitory properties against S. aureus.
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Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract "430D-F5" against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2-32 µg mL-1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections.
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Anacardiaceae/química , Percepción de Quorum , Enfermedades de la Piel/patología , Alelos , Animales , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Modelos Animales de Enfermedad , Proteínas Hemolisinas/farmacología , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Microbiota , Necrosis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Percepción de Quorum/efectos de los fármacos , Piel/efectos de los fármacos , Piel/microbiología , Piel/patología , Enfermedades de la Piel/microbiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/patología , Toxinas Biológicas/química , Toxinas Biológicas/toxicidad , Virulencia/efectos de los fármacosRESUMEN
Schisandra chinensis (Chinese starvine) is a popular dietary supplement with a rich history of use in traditional Chinese medicine. Schisandra glabra (bay starvine) is the only North American representative of the genus, and little is known about its history of traditional use, chemistry, and potential biological activity. In this study, we conducted comparative high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis on S. glabra and S. chinensis fruits. Additional characterization of S. glabra was performed by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS). Quantitative analysis of four bioactive marker compounds revealed that S. glabra does not have statistically higher levels of schisandrin A or schisandrol B than S. chinensis. S. glabra has lower levels of schisandrol A and γ-schisandrin. Total phenolic contents of the two species' fruits were not statistically different. S. glabra had higher total tannin content than S. chinensis. We discuss the relevance of this analytical analysis to the study of S. glabra as a potential dietary supplement ingredient and give specific consideration to the conservation challenges involved in commercially developing a regionally threatened species, even in semicultivated conditions.
Asunto(s)
Suplementos Dietéticos , Fitoquímicos/análisis , Extractos Vegetales/análisis , Schisandra/química , Cromatografía Líquida de Alta Presión , Ciclooctanos/análisis , Dioxoles/análisis , Frutas/química , Lignanos/análisis , Medicina Tradicional China , Fenoles/análisis , Compuestos Policíclicos/análisis , Schisandra/clasificación , Espectroscopía Infrarroja por Transformada de Fourier , Taninos/análisisRESUMEN
Staphylococcus aureus is a leading cause of hospital-acquired infections. It is listed among the top "serious threats" to human health in the USA, due in large part to rising rates of resistance. Many S. aureus infections are recalcitrant to antibiotic therapy due to their ability to form a biofilm, which acts not only as a physical barrier to antibiotics and the immune system, but results in differences in metabolism that further restricts antibiotic efficacy. Development of a modular strategy to synthesize a library of phenolic glycosides allowed for bioactivity testing and identification of anti-biofilm compounds within an extract of the elmleaf blackberry (Rubus ulmifolius). Two ellagic acid (EA) derivatives, EA xyloside and EA rhamnoside, have been identified as components of the Rubus extract. In addition, EA rhamnoside has been identified as an inhibitor of biofilm formation, with activity comparable to the complex extract 220D-F2 (composed of a mixture of EA glycosides), and confirmed by confocal laser scanning microscopy analyses.