Antifungal Effects of Drimane Sesquiterpenoids Isolated from Drimys winteri against Gaeumannomyces graminis var. tritici.

Gaeumannomyces graminis var. tritici is a soilborne pathogen that causes "take-all" disease, affecting cereal roots. In wheat, G. graminis var. tritici is the most important biotic factor, causing around 30 to 50% losses of yield. Chemical control of this fungal disease is difficult because G. graminis var. tritici is able to reside for a long time in soils. Therefore, the development of environmentally friendly biotechnological strategies to diminish the incidence of soilborne diseases is highly desirable. Natural products are a promising strategy for biocontrol of plant pathogens. A special emphasis is on medicinal plants due to their reported fungitoxic effects. Drimys winteri (canelo) is a medicinal plant that is widely used by the Mapuche ethnic group from Chile due to its anti-inflammatory activity. In addition, inhibitory effects of canelo against phytopathogenic fungi and pest insects have been reported. In this study, we isolated, purified, and identified six drimane sesquiterpenoid compounds from canelo (drimenin, drimenol, polygodial, isodrimeninol, valdiviolide, and drimendiol). Then, we evaluated their antimicrobial effects against G. graminis var. tritici. Compounds were identified by comparing Fourier-transform infrared spectroscopy (FTIR) data and the retention time in thin-layer chromatography (TLC) with those of pure standards. The putative antagonistic effects were confirmed by assessing hyphal cell wall damage using confocal microscopy and lipid peroxidation. Here, we reported the high potential of drimane sesquiterpenoids as natural antifungals against G. graminis var. tritici. Polygodial and isodrimeninol were the most effective, with 50% lethal concentrations (LC50s) between 7 and 10 µg ml-1 and higher levels of fungal lipid peroxidation seen. Accordingly, natural sesquiterpenoids purified from canelo are biologically active against G. graminis var. tritici and could be used as natural biofungicides for sustainable agriculture.IMPORTANCE More than two billion tons of pesticides are used every year worldwide. An interesting sustainable alternative to control plant pathogens is the use of natural products obtained from plants, mainly medicinal plants that offer secondary metabolites important to human/animal health. In this study, we isolated and identified six pure drimane sesquiterpenoids obtained from the bark of Drimys winteri Additionally, we evaluated their antifungal activities against Gaeumannomyces graminis (the main biotic factor affecting cereal production, especially wheat) by assessing fungal cell wall damage and lipid peroxidation. The compounds obtained showed important antifungal properties against G. graminis var. tritici, mainly isodrimenol, which was the second-most-active compound after polygodial, with an LC50 against G. graminis var. tritici of around 9.5 µg ml-1 This information could be useful for the development of new natural or hemisynthetic antifungal agents against soilborne phytopathogens that could be used in green agriculture.

[Skin reactivity frequency to aeroallergens in patients with clinical symptoms of allergic disease]. / Frecuencia de reactividad cutánea hacia antígenos inhalables en pacientes con cuadro clínico de enfermedad alérgica.

BACKGROUND: Allergic diseases diagnosis must be based on adequate allergological anamnesis and an immunological sensitization test; the most sensitive and specific is the skin prick test. OBJECTIVE: To determine the frequency of skin reactivity to aeroallergens, by age groups, in patients of the Department of Allergy and Clinical Immunology of the Hospital Universitario de Puebla, in Mexico. METHODS: A cross-sectional study was conducted that included patients aged 2 to 64 years with symptoms suggestive of allergic disease, in which skin prick tests with aeroallergens were performed; the diagnostic criteria were those of international guidelines. Frequencies, percentages and dispersion measures were calculated. RESULTS: Of 173 patients, 63 % were females. Mean age was 22.3 years. The frequency of skin reactivity for Quercus sp. was 12.72 %, for Periplaneta americana, 9.83 %, for Dermatophagoides farinae, 9.25 %, for Cynodon dactylon, 8.09 %, for Blatella germanica, 8.09 %, for Holcus halepensis, 6.94 %, for Dermatophagoides pteronyssinus, 6.36 %, for Schinus molle, 5.78 %, for Fraxinus uhdei, 5.20 %, for Lolium perenne, 5.20 %, for Ambrosia eliator, 5.20 % and for Artemisa tridentata, 4.62 %. CONCLUSION: Although Dermatophagoides are the most frequently reported aeroallergens, the most common aeroallergen in this study was pollen, probably owing to geographical and environmental factors, although this was not observed in the analysis by age groups.

Antecedentes: El diagnóstico de las enfermedades alérgicas debe basarse en la historia clínica alergológica adecuada y en una prueba inmunológica de sensibilización; la de mayor sensibilidad y especificidad es la prueba cutánea por punción. Objetivo: Determinar la frecuencia de la reactividad cutánea hacia aeroalérgenos, por grupos etarios, en pacientes del Servicio de Alergia e Inmunología Clínica del Hospital Universitario de Puebla, México. Métodos: Se realizó estudio transversal que incluyó a pacientes de 2 a 64 años de edad, con síntomas sugestivos de enfermedad alérgica, en quienes se realizaron pruebas cutáneas con aeroalérgenos; los criterios diagnósticos fueron los de las guías internacionales. Se calcularon frecuencias, porcentajes y medidas de dispersión. Resultados: De 173 pacientes, 63 % fue del sexo femenino. La edad media fue de 22.3 años. La frecuencia de la reactividad cutánea para Quercus sp. fue 12.72 %, Periplaneta americana 9.83 %, Dermatophagoides farinae 9.25 %, Cynodon dactylon 8.09 %, Blatella germanica 8.09 %, Holcus halepensis 6.94 %, Dermatophagoides pteronyssinus 6.36 %, Schinus molle 5.78 %, Fraxinus uhdei 5.20 %, Lolium perenne 5.20 %, Ambrosia eliator 5.20 % y Artemisa tridentata 4.62 %. Conclusión: Los Dermatophagoides son los aeroalérgenos más identificados, pero en el presente estudio fue más común un polen, probablemente debido a factores geográficos-medioambientales, aunque no fue así en el análisis por grupos etarios.

Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression.

Fibroblast growth factor 23 (FGF 23) and phosphocalcic metabolism in chronic kidney disease.

BACKGROUND AND OBJECTIVES: The ample information available in relation to FGF 23, calcium, phosphorus, PTH, and 25/1,25 vitamin D has allowed us to define consistent values for each variable in each stage of chronic kidney disease (CKD). These values can define early stages, prognostic issues, and new treatment targets. We describe a cross-sectional study of these parameters in patients with different stages of CKD. METHOD: We measured FGF 23 by ELISA (intact molecule, Kainos Laboratory, Japan), calcium, phosphorus, PTH and vit D by standard methods. RESULTS: We examined 251 patients, 146 of which were men, with a mean age of 62.5 (11.5) years and 43% prevalence of type II DM. Levels of FGF 23 rose progressively, in a very significant manner, in correlation with the evolution of CKD, especially in stage 4 as compared to stage 1 (110.61 ng/L vs 31.32 ng/L). The same happened with iPTH values. Additionally, levels of 1,25 vitamin D decreased in a similar manner. Calcium values did not change. 25 vit D3 levels were low at all times and showed no tendency for a steady decline. Phosphorus rose in stage 4 CKD. Levels of FGF 23 were negatively correlated with renal function indicators and positively correlated with PTH and P. CONCLUSIONS: During the evolution of CKD, changes of FGF 23 and PTH would be the earliest markers. Calcium and 25 vit D3 do not vary with changes in the progression of CKD. Values of FGF 23 show an important correlation with PTH, 1,25 vit D3, P and estimated glomerular filtration rate.