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1.
Proc Natl Acad Sci U S A ; 120(2): e2217303120, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36595703

RESUMEN

There are growing calls for conservation frameworks that, rather than breaking the relations between people and other parts of nature, capture place-based relationships that have supported social-ecological systems over the long term. Biocultural approaches propose actions based on biological conservation priorities and cultural values aligned with local priorities, but mechanisms that allow their global uptake are missing. We propose a framework to globally assess the biocultural status of specific components of nature that matter to people and apply it to culturally important species (CIS). Drawing on a literature review and a survey, we identified 385 wild species, mostly plants, which are culturally important. CIS predominate among Indigenous peoples (57%) and ethnic groups (21%). CIS have a larger proportion of Data-Deficient species (41%) than the full set of International Union for Conservation of Nature (IUCN) species (12%), underscoring the disregard of cultural considerations in biological research. Combining information on CIS biological conservation status (IUCN threatened status) and cultural status (language vitality), we found that more CIS are culturally Vulnerable or Endangered than they are biologically and that there is a higher share of bioculturally Endangered or Vulnerable CIS than of either biologically or culturally Endangered CIS measured separately. Bioculturally Endangered or Vulnerable CIS are particularly predominant among Indigenous peoples, arguably because of the high levels of cultural loss among them. The deliberate connection between biological and cultural values, as developed in our "biocultural status" metric, provides an actionable way to guide decisions and operationalize global actions oriented to enhance place-based practices with demonstrated long-term sustainability.


Asunto(s)
Conservación de los Recursos Naturales , Medio Social , Humanos , Animales , Pueblos Indígenas , Etnicidad , Biodiversidad , Especies en Peligro de Extinción
2.
Nature ; 571(7764): 257-260, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31217589

RESUMEN

Increasing global food demand, low grain reserves and climate change threaten the stability of food systems on national to global scales1-5. Policies to increase yields, irrigation and tolerance of crops to drought have been proposed as stability-enhancing solutions1,6,7. Here we evaluate a complementary possibility-that greater diversity of crops at the national level may increase the year-to-year stability of the total national harvest of all crops combined. We test this crop diversity-stability hypothesis using 5 decades of data on annual yields of 176 crop species in 91 nations. We find that greater effective diversity of crops at the national level is associated with increased temporal stability of total national harvest. Crop diversity has stabilizing effects that are similar in magnitude to the observed destabilizing effects of variability in precipitation. This greater stability reflects markedly lower frequencies of years with sharp harvest losses. Diversity effects remained robust after statistically controlling for irrigation, fertilization, precipitation, temperature and other variables, and are consistent with the variance-scaling characteristics of individual crops required by theory8,9 for diversity to lead to stability. Ensuring stable food supplies is a challenge that will probably require multiple solutions. Our results suggest that increasing national effective crop diversity may be an additional way to address this challenge.


Asunto(s)
Productos Agrícolas/clasificación , Productos Agrícolas/provisión & distribución , Abastecimiento de Alimentos/métodos , Abastecimiento de Alimentos/estadística & datos numéricos , Geografía , Riego Agrícola/estadística & datos numéricos , Biodiversidad , Calorimetría , Productos Agrícolas/crecimiento & desarrollo , Sequías/estadística & datos numéricos , Fertilizantes/provisión & distribución , Modelos Teóricos , Probabilidad , Lluvia , Temperatura
3.
Rev Med Suisse ; 19(831): 1200-1205, 2023 Jun 14.
Artículo en Francés | MEDLINE | ID: mdl-37314261

RESUMEN

Neurocognitive disorders (TNC) are of a public health concern. An early and accurate diagnosis is important to tailor a personalised care. We illustrate the importance of a graduated etiological diagnostic approach centered on the clinical presentation employing the case of a patient with a progressive neurovisual disorder suggestive of a common form of Alzheimer's disease. The results of the CSF biomarkers analysis argue against this diagnosis and justifies seeking a Lewy body disease as a differential diagnosis even if all the clinical criteria are initially incomplete. In this article, we illustrate the progressive and graduated approach in the use of complementary medical tests available for reliable and early diagnosis in order to optimise the care plan and predict clinical progress and needs.


Les troubles neurocognitifs (TNC) sont un enjeu de santé publique. Un diagnostic précoce et précis est important pour une prise en charge personnalisée. Nous illustrons l'intérêt d'une démarche diagnostique étiologique graduelle centrée sur la clinique à partir du cas d'un patient atteint d'un trouble neurovisuel progressif suggérant une forme commune de maladie d'Alzheimer. L'analyse des biomarqueurs du LCR argumente en défaveur de ce diagnostic et justifie de rechercher comme diagnostic différentiel une maladie à corps de Lewy même si l'ensemble des critères cliniques sont initialement incomplets. Nous discutons dans cet article la démarche progressive et graduelle dans l'emploi des examens complémentaires à disposition pour un diagnostic fiable et précoce afin d'optimiser le plan de soins et de prédire l'évolution clinique et les besoins.


Asunto(s)
Enfermedad de Alzheimer , Trastornos Neurocognitivos , Humanos , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/etiología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/etiología , Diagnóstico Diferencial , Salud Pública
4.
Proc Biol Sci ; 289(1983): 20221542, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36168758

RESUMEN

Over the course of history, humans have moved crops from their regions of origin to new locations across the world. The social, cultural and economic drivers of these movements have generated differences not only between current distributions of crops and their climatic origins, but also between crop distributions and climate suitability for their production. Although these mismatches are particularly important to inform agricultural strategies on climate change adaptation, they have, to date, not been quantified consistently at the global level. Here, we show that the relationships between the distributions of 12 major food crops and climate suitability for their yields display strong variation globally. After investigating the role of biophysical, socio-economic and historical factors, we report that high-income world regions display a better match between crop distribution and climate suitability. In addition, although crops are farmed predominantly in the same climatic range as their wild progenitors, climate suitability is not necessarily higher there, a pattern that reflects the legacy of domestication history on current crop distribution. Our results reveal how far the global distribution of major crops diverges from their climatic optima and call for greater consideration of the multiple dimensions of the crop socio-ecological niche in climate change adaptive strategies.


Asunto(s)
Cambio Climático , Productos Agrícolas , Agricultura/métodos , Ecosistema , Granjas , Humanos
5.
6.
Proc Natl Acad Sci U S A ; 112(43): 13411-6, 2015 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-26460005

RESUMEN

Managing multiple ecosystem services (ES), including addressing trade-offs between services and preventing ecological surprises, is among the most pressing areas for sustainability research. These challenges require ES research to go beyond the currently common approach of snapshot studies limited to one or two services at a single point in time. We used a spatiotemporal approach to examine changes in nine ES and their relationships from 1971 to 2006 across 131 municipalities in a mixed-use landscape in Quebec, Canada. We show how an approach that incorporates time and space can improve our understanding of ES dynamics. We found an increase in the provision of most services through time; however, provision of ES was not uniformly enhanced at all locations. Instead, each municipality specialized in providing a bundle (set of positively correlated ES) dominated by just a few services. The trajectory of bundle formation was related to changes in agricultural policy and global trends; local biophysical and socioeconomic characteristics explained the bundles' increasing spatial clustering. Relationships between services varied through time, with some provisioning and cultural services shifting from a trade-off or no relationship in 1971 to an apparent synergistic relationship by 2006. By implementing a spatiotemporal perspective on multiple services, we provide clear evidence of the dynamic nature of ES interactions and contribute to identifying processes and drivers behind these changing relationships. Our study raises questions about using snapshots of ES provision at a single point in time to build our understanding of ES relationships in complex and dynamic social-ecological systems.


Asunto(s)
Agricultura/métodos , Conservación de los Recursos Naturales/historia , Conservación de los Recursos Naturales/métodos , Ecosistema , Modelos Teóricos , Conservación de los Recursos Naturales/estadística & datos numéricos , Historia del Siglo XX , Historia del Siglo XXI , Política Pública , Quebec , Factores Socioeconómicos , Análisis Espacial , Factores de Tiempo
7.
Rev Med Suisse ; 11(498): 2338-41, 2015 Dec 09.
Artículo en Francés | MEDLINE | ID: mdl-26790241

RESUMEN

Demographic evolution results in a growing use of emergency department by elderly patients. They require special care to avoid any further degradation of cognitive and functional abilities already compromised by the disease or injury that led them to hospital in the first place. Through a clinical case, we list the risks related to the care of these particular patients in the emergency department. Early recognition of those risks and careful management of these patients' specific needs can significantly contribute to reduce lengths of stay, an important outcome from both the individual patient's and society's perspective.


Asunto(s)
Atención a la Salud/organización & administración , Servicio de Urgencia en Hospital/organización & administración , Necesidades y Demandas de Servicios de Salud , Factores de Edad , Anciano , Humanos , Tiempo de Internación , Masculino , Riesgo
8.
Rev Med Suisse ; 11(456-457): 124-8, 2015 Jan 14.
Artículo en Francés | MEDLINE | ID: mdl-25799668

RESUMEN

The main pharmacovigilance updates in 2014 are reviewed. Ivabradine: increased risk of cardiovascular death and myocardial infarction in patients with symptomatic angina treated with high dosages. Clopidogrel: rare observations of acquired hemophilia. Orlistat: may reduce the absorption of HIV antiretrovirals. Ponatinib: increased risk of arteriopathy and thrombosis. Axitinib: significant risk of heart failure (class effect). Tocilizumab: possible causal relationship with the emergence or aggravation of psoriasis. Lithium: hypercalcemia and hyperparathyroidism commonly observed. Sildenalfil: suspected causal association with melanoma, so far not proven, Methylphenidate: rare observations of priapism. St John's wort (Hypericum): reduced effectiveness of hormonal contraceptives, including implants.


Asunto(s)
Farmacovigilancia , Humanos
9.
Rev Med Suisse ; 10(412-413): 119-22, 2014 Jan 15.
Artículo en Francés | MEDLINE | ID: mdl-24558915

RESUMEN

The main pharmacovigilance updates in 2013 are reviewed. Nitrofurantoin: lower efficacy and an increased risk of adverse events when creatinine clearance is below 60 ml/min. Dabigatran: contraindicated in patients with mechanical heart valves. Azithromycin: QT prolongation and increased risk of death. Zolpidem: towards a lower dosage. Roflumilast: avoid in patients known or at risk for mood disorders. Retigabine: indication restricted to last-line use and new monitoring requirements after reports of pigment changes in retina and other tissues. Telaprevir and rituximab: severe mucocutaneous reactions. Fingolimod: rare cases of progressive multifocal leucoencephalopathy. Tolvaptan: potential for hepatotoxicity. Nicotinic acid/laropiprant: suspension of marketing authorization as benefits no longer outweigh risks.


Asunto(s)
Nitrofurantoína/efectos adversos , Farmacovigilancia , Aminopiridinas/efectos adversos , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Azitromicina/efectos adversos , Benzamidas/efectos adversos , Carbamatos/efectos adversos , Ciclopropanos/efectos adversos , Humanos , Oligopéptidos/efectos adversos , Fenilendiaminas/efectos adversos , Piridinas/efectos adversos , Rituximab , Zolpidem
10.
Proc Natl Acad Sci U S A ; 107(17): 7823-8, 2010 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-20385814

RESUMEN

The scale and nature of pre-Columbian human impacts in Amazonia are currently hotly debated. Whereas pre-Columbian people dramatically changed the distribution and abundance of species and habitats in some parts of Amazonia, their impact in other parts is less clear. Pioneer research asked whether their effects reached even further, changing how ecosystems function, but few in-depth studies have examined mechanisms underpinning the resilience of these modifications. Combining archeology, archeobotany, paleoecology, soil science, ecology, and aerial imagery, we show that pre-Columbian farmers of the Guianas coast constructed large raised-field complexes, growing on them crops including maize, manioc, and squash. Farmers created physical and biogeochemical heterogeneity in flat, marshy environments by constructing raised fields. When these fields were later abandoned, the mosaic of well-drained islands in the flooded matrix set in motion self-organizing processes driven by ecosystem engineers (ants, termites, earthworms, and woody plants) that occur preferentially on abandoned raised fields. Today, feedbacks generated by these ecosystem engineers maintain the human-initiated concentration of resources in these structures. Engineer organisms transport materials to abandoned raised fields and modify the structure and composition of their soils, reducing erodibility. The profound alteration of ecosystem functioning in these landscapes coconstructed by humans and nature has important implications for understanding Amazonian history and biodiversity. Furthermore, these landscapes show how sustainability of food-production systems can be enhanced by engineering into them follows that maintain ecosystem services and biodiversity. Like anthropogenic dark earths in forested Amazonia, these self-organizing ecosystems illustrate the ecological complexity of the legacy of pre-Columbian land use.


Asunto(s)
Agricultura/historia , Agricultura/métodos , Ecosistema , Conducta Espacial/fisiología , Arqueología , Guyana Francesa , Historia Antigua , Historia Medieval , Humanos , Suelo/análisis
11.
Rev Med Suisse ; 9(405): 2054-8, 2013 Nov 06.
Artículo en Francés | MEDLINE | ID: mdl-24308143

RESUMEN

Elderly people are prone to drug-induced adverse events (AEs), which often manifest as an atypical clinical picture. The differential diagnosis of any new symptom or alteration in the general state of health in the elderly must, therefore, include AEs. This article offers a practical tool designed to help clinicians to rapidly identify which drugs may induce which kind of frequent symptoms or syndromes.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Estado de Salud , Factores de Edad , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Humanos
12.
Ann Bot ; 110(5): 943-51, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22875811

RESUMEN

BACKGROUND AND AIMS: Plant defence traits against herbivores incur production costs that are usually difficult to measure. However, estimating these costs is a prerequisite for characterizing the plant defence strategy as a whole. Myrmecophytes are plants that provide symbiotic ants with specialized nesting cavities, called domatia, in exchange for protection against herbivores. In the particular case of stem domatia, production of extra wood seems to be the only associated cost, making this indirect defence trait a particularly suitable model for estimating the cost of defence. METHODS: Measurements were made of growth pattern and cumulative production cost of domatia over secondary growth in the myrmecophyte Leonardoxa africana subsp. africana, whose internodes display both a solid basal segment and a hollow distal part (the domatium), thus allowing paired comparison of investment in wood. KEY RESULTS: Previous studies showed that 'overconstruction' of the hollow part of internodes during primary growth is needed for mechanical support. In this study, it is shown that the relationship between the woody cross-sectional area of the solid and hollow parts of internodes is negatively allometric at the beginning of secondary growth and nearly isometric later on. Thus, in hollow stems, the first phase of slow secondary growth compensates for the 'overconstruction' of the ring of wood during primary growth. Moreover, the cumulative production cost of a domatium (estimated as the additional volume of wood required for a hollow stem compared with a solid one) is very high at the beginning of secondary growth and then quickly tends to zero. CONCLUSIONS: Making domatia incurs high costs early in ontogeny, costs that are then amortized later in development of stems and of individual plants. Characterizing ontogenetic variation of the net cost of this peculiar defence mechanism will help us build more accurate theoretical models of resource allocation in myrmecophytes.


Asunto(s)
Fabaceae/crecimiento & desarrollo , Tallos de la Planta/crecimiento & desarrollo , Animales , Hormigas/fisiología , Fabaceae/fisiología , Interacciones Huésped-Parásitos , Modelos Biológicos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Tallos de la Planta/fisiología , Simbiosis , Madera/crecimiento & desarrollo , Madera/fisiología
13.
Rev Med Suisse ; 8(361): 2109-14, 2012 Nov 07.
Artículo en Francés | MEDLINE | ID: mdl-23173345

RESUMEN

Providing care to multimorbid older patients is complex, not only because of the coexistence of multiple chronic conditions, but also because of their frequent intrication with psychological and social problems. This article describes a guide for clinicians to assess and manage multimorbid older patients. This guide was adapted from the work of a group of expert US geriatricians. It proposes seven steps: identification of the main problem; identification of patients' preferences; setting of goals of care; estimation of life expectancy; identification of relevant evidence in the literature; revision of the plan of care; and discussion of the options with the patient. The use of this guide is illustrated by a clinical case.


Asunto(s)
Envejecimiento , Diabetes Mellitus Tipo 2/terapia , Insuficiencia Cardíaca/terapia , Hipertensión/terapia , Isquemia Miocárdica/terapia , Enfermedad Pulmonar Obstructiva Crónica/terapia , Trastornos del Sueño-Vigilia/terapia , Anciano de 80 o más Años , Algoritmos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Evaluación Geriátrica , Geriatría , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Hipertensión/complicaciones , Hipertensión/mortalidad , Esperanza de Vida , Masculino , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/mortalidad , Guías de Práctica Clínica como Asunto , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Factores de Riesgo , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/mortalidad , Fumar/efectos adversos , Resultado del Tratamiento
14.
Rev Med Suisse ; 7(292): 923-7, 2011 Apr 27.
Artículo en Francés | MEDLINE | ID: mdl-21674897

RESUMEN

Efficacy of iron therapy, whether oral or intravenous, on biological markers of body iron stores is well recognized in medical literature, but current studies are heterogeneous, of sometimes dubious quality, and rarely address clinical outcomes. Precise practical guidelines appear available only for indications related to kidney disease. First-line intravenous use is reserved for situations comprising chronic renal failure, or patients presenting with malabsorption syndromes such as in inflammatory bowel disease. In all other situations, because of the non-negligible risk of hypersensitivity reactions, intravenous iron use is considered justified only in clinically sustained indications, for patients in whom oral administration of iron is unsatisfactory or impossible.


Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Hierro/uso terapéutico , Oligoelementos/uso terapéutico , Anemia Ferropénica/etiología , Humanos
15.
Curr Biol ; 31(19): R1154-R1158, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34637721

RESUMEN

A confluence of discoveries in ecology and agriculture suggests that biodiversity can help address the sustainability problems facing modern intensive agriculture. Here we explore several questions related to this possibility. Can increases in national crop diversity help increase the stability and security of national food systems? Can practices based on greater crop biodiversity produce yields that compete with those obtained through the long-standing, high-input monoculture model? What are the appropriate levels and combinations of crops to be used? We highlight recent research that suggests it is time to begin unlocking the agricultural potential of biodiversity - from the level of crop genetic diversity to species diversity - and to do so on spatial scales from individual fields to nations. Recent research suggests that the biodiversification of agriculture may lead to greater and more stable yields, decrease land clearing, and lower the use of harmful agrochemicals.


Asunto(s)
Biodiversidad , Productos Agrícolas , Agricultura , Ecosistema , Seguridad Alimentaria , Abastecimiento de Alimentos
16.
Sci Rep ; 11(1): 4922, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649430

RESUMEN

Ensuring the temporal stability of national food production is crucial for avoiding sharp drops in domestic food availability. The average stability of individual crop yields and asynchrony among crop yield fluctuations are two candidate mechanisms to stabilize national food production. However, the quantification of their respective influence on the stability of national food production is lacking, as is the identification of the factors regulating both mechanisms. Using yield data for 138 crops and 115 countries over a 50-year period, we first show that the stability of total national yield mostly relies on the fluctuations of the yield of crops covering the largest share of cropland. The average yield stability of these crops exert a stabilizing effect on national food production that is twice as important as the one of the asynchronous yield fluctuations among them. Climate variability reduces the stability of national food production by synchronizing yield fluctuations among crops and destabilizing the yield of individual crops. However, our results suggest that increasing crop diversity can counteract the synchronizing effects of climate variability by enhancing asynchronous dynamics among crops. Irrigation can promote the average stability of individual crop yields but cannot compensate for the destabilizing effect of climate variability. Considering both the response of each crop to climatic variations and the dynamics emerging from crop baskets will help agricultural policies to ensure stable food supply at the national level.

17.
Bioorg Med Chem ; 17(23): 8123-37, 2009 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-19833521

RESUMEN

The synthesis of some novel azasteroids and thiasteroids based on a pregnan nucleus with a Delta7 double bond in two to five steps from the key aldehyde (3S,20S)-20-formylpregn-7-en-3-yl acetate has been disclosed herein. These compounds were evaluated as potential inhibitors of the enzyme Delta24-sterol methyltransferase (24-SMT), which is a key enzyme in the biosynthesis of ergosterol, and for their effects on the growth of the yeast Yarrowia lipolytica. Most of the side chain modified analogues were recognized as 24-SMT inhibitors, and in particular the 23-azasteroids 5f-5i and the 24-azasteroid 11 showed potent antifungal activity. The target enzyme could be identified unambiguously using an improved whole-cell assay combined with GC-MS analysis of the sterol pattern resulting upon incubation with the inhibitors.


Asunto(s)
Antifúngicos/síntesis química , Azaesteroides/síntesis química , Inhibidores Enzimáticos/síntesis química , Ergosterol/biosíntesis , Metiltransferasas/metabolismo , Antifúngicos/química , Antifúngicos/farmacología , Azaesteroides/química , Azaesteroides/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Metiltransferasas/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Yarrowia/crecimiento & desarrollo
18.
Ecology ; 100(7): e02719, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31081945

RESUMEN

Because natural ecosystems are complex, it is difficult to predict how their variability scales across space and levels of organization. The species-insurance hypothesis predicts that asynchronous dynamics among species should reduce variability when biomass is aggregated either from local species populations to local multispecies communities, or from metapopulations to metacommunities. Similarly, the spatial-insurance hypothesis predicts that asynchronous spatial dynamics among either local populations or local communities should stabilize metapopulation biomass and metacommunity biomass, respectively. In combination, both species and spatial insurance reduce variation in metacommunity biomass over time, yet these insurances are rarely considered together in natural systems. We partitioned the extent that species insurance and spatial insurance reduced the annual variation in macroalgal biomass in a southern California kelp forest. We quantified variability and synchrony at two levels of organization (population and community) and two spatial scales (local plots and region) and quantified the strength of species and spatial insurance by comparing observed variability and synchrony in aggregate biomass to null models of independent species or spatial dynamics based on cyclic-shift permutation. Spatial insurance was weak, presumably because large-scale oceanographic processes in the study region led to high spatial synchrony at both population- and community-level biomass. Species insurance was stronger due to asynchronous dynamics among the metapopulations of a few common species. In particular, a regional decline in the dominant understory kelp species Pterygophora californica was compensated for by the rise of three subdominant species. These compensatory dynamics were associated with positive values of the Pacific Decadal Oscillation, indicating that differential species tolerances to warmer temperature and nutrient-poor conditions may underlie species insurance in this system. Our results illustrate how species insurance can stabilize aggregate community properties in natural ecosystems where environmental conditions vary over broad spatial scales.


Asunto(s)
Ecosistema , Kelp , Biomasa , California , Bosques , Dinámica Poblacional
19.
Steroids ; 73(3): 299-308, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18164739

RESUMEN

Inhibition of cholesterol biosynthesis offers the opportunity for treatment of cardiovascular diseases. Numerous enzymes are involved in the post-squalene part of this biosynthesis, and selective inhibitors for almost all of the enzymes involved there have been described in literature. The only exception is the enzyme lathosterol oxidase (EC 1.14.21.6), for which up to now no selective inhibitor has been found. Up to date only triarimol has been reported as a weak inhibitor. In this paper we report on lathosterol side chain amides as a new class of selective lathosterol oxidase inhibitors. To study the influence of different sterol amides on inhibition of this enzyme, numerous compounds were prepared and the sterol patterns resulting from incubation of HL 60 cells with these enzyme inhibitors were monitored in a whole cell screening assay by means of GC/MS analysis. Small alkyl residues at the amide nitrogen (hydrogen and methyl) lead to an inhibition of the enzyme Delta24-reductase, the N-ethyl and N-propyl derivatives show a dual action, inhibiting both Delta24-reductase and lathosterol oxidase. Lathosterol-derived amides with larger substituents (butyl, isobutyl, tert-butyl, pentyl) at the amide nitrogen were found to be selective inhibitors of lathosterol oxidase. The corresponding 3beta-acetoxy derivatives showed comparable activities and can be considered as prodrugs, since they are transformed into the 3beta-hydroxy derivatives under the test conditions, as proven by HPLC analysis.


Asunto(s)
Colesterol/química , Colesterol/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Amidas/química , Amidas/farmacología , Cromatografía Líquida de Alta Presión , Inhibidores Enzimáticos/clasificación , Cromatografía de Gases y Espectrometría de Masas , Células HL-60 , Humanos
20.
Phytopathology ; 96(11): 1278-86, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18943966

RESUMEN

ABSTRACT The prophylactic efficiency of Milsana against powdery mildew was evaluated on wheat (Triticum aestivum). A single short spraying on 10-day-old plantlets reduced the infection level by 85% and two long sprayings led to the total restriction of the disease. Although microscopic studies showed that Milsana treatments enhance hydrogen peroxide accumulation at the fungal penetration site, biochemical analysis did not allow us to correlate this accumulation with the activation of several enzyme activities involved in active oxygen species (AOS) metabolism. Only lipoxygenase activity, which is involved in both AOS metabolism and lipid peroxidation, showed a 26 to 32% increase 48-h posttreatment in leaves infiltrated with Milsana. This weak effect of Milsana on wheat lipid metabolism was confirmed at the lipid peroxidation level, which surprisingly, was shown to decrease in treated plants. In order to explain the high efficacy of Milsana, the fungistatic effect on conidia germination was also examined. In planta, we showed that a Milsana treatment resulted in a higher proportion of abnormally long appressorial germ tubes, whereas in vitro, it dramatically inhibited fungal conidia germination. The partial activity of Milsana in terms of defense response induction in the wheat/powdery mildew pathosystem and its newly described direct fungistatic activity are discussed.

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