Natural Substances as Valuable Alternative for Improving Conventional Antifungal Chemotherapy: Lights and Shadows.

Fungi are eukaryotic organisms with relatively few pathogenic members dangerous for humans, usually acting as opportunistic infections. In the last decades, several life-threatening fungal infections have risen mostly associated with the worldwide extension of chronic diseases and immunosuppression. The available antifungal therapies cannot combat this challenge because the arsenal of compounds is scarce and displays low selective action, significant adverse effects, and increasing resistance. A growing isolation of outbreaks triggered by fungal species formerly considered innocuous is being recorded. From ancient times, natural substances harvested from plants have been applied to folk medicine and some of them recently emerged as promising antifungals. The most used are briefly revised herein. Combinations of chemotherapeutic drugs with natural products to obtain more efficient and gentle treatments are also revised. Nevertheless, considerable research work is still necessary before their clinical use can be generally accepted. Many natural products have a highly complex chemical composition, with the active principles still partially unknown. Here, we survey the field underlying lights and shadows of both groups. More studies involving clinical strains are necessary, but we illustrate this matter by discussing the potential clinical applications of combined carnosic acid plus propolis formulations.

Insight into the Antifungal Effects of Propolis and Carnosic Acid-Extension to the Pathogenic Yeast Candida glabrata: New Propolis Fractionation and Potential Synergistic Applications.

Fungi have traditionally been considered opportunistic pathogens in primary infections caused by virulent bacteria, protozoan, or viruses. Consequently, antimycotic chemotherapy is clearly less developed in comparison to its bacterial counterpart. Currently, the three main families of antifungals (polyenes, echinocandins, and azoles) are not sufficient to control the enormous increase in life-threatening fungal infections recorded in recent decades. Natural substances harvested from plants have traditionally been utilized as a successful alternative. After a wide screening of natural agents, we have recently obtained promising results with distinct formulations of carnosic acid and propolis on the prevalent fungal pathogens Candida albicans and Cryptococcus neoformans. Here, we extended their use to the treatment against the emerging pathogenic yeast Candida glabrata, which displayed lower susceptibility in comparison to the fungi mentioned above. Taking into account the moderate antifungal activity of both natural agents, the antifungal value of these combinations has been improved through the obtention of the hydroethanolic fractions of propolis. In addition, we have demonstrated the potential clinical application of new therapeutical designs based on sequential pre-treatments with carnosic/propolis mixtures, followed by exposure to amphotericin B. This approach increased the toxic effect induced by this polyene.

Pitcairniaabscondita (Pitcairnioideae, Bromeliaceae), a hidden novelty from north-western Jalisco, Mexico.

Pitcairniaabscondita sp. nov., known until now only from the Municipalities of Cabo Corrientes, Mascota, Puerto Vallarta, San Sebastián del Oeste and Talpa de Allende in the State of Jalisco, Mexico, is here described and illustrated. The new taxon was confused with P.imbricata for long time, but differs from this species by its green floral bracts with the apex divergent to spreading (vs. red and appressed) and by the appendiculate at the base chartreuse-green petals (vs. not appendiculate yellow petals). Images and a distribution map of the taxa are presented.

ResumenSe describe e ilustra Pitcairniaabscondita sp. nov., conocida hasta ahora únicamente de los municipios de Cabo Corrientes, Mascota, Puerto Vallarta, San Sebastián del Oeste y Talpa de Allende, en el estado de Jalisco, México. El nuevo taxon fue por largo tiempo confundido con P.imbricata, pero difiere de la misma por sus brácteas florales verdes con el ápice divergente a extendido (vs. brácteas rojas y adpresas) y por sus pétalos verdes chartreuse con apéndices en la base (vs. pétalos amarillos sin apéndices en la base). Se incluyen imágenes y un mapa de distribución de las especies.

A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans.

Current antifungal chemotherapy against the prevalent basidiomycete Cryptococcus neoformans displays some drawbacks. This pathogenic fungus is refractory to echinocandins, whereas conventional treatment with amphotericin B plus 5-fluorocytosine has a limited efficacy. In this study, we explored the potential cryptococcal activity of some natural agents. After conducting a screening test with a set of propolis from different geographical areas, we selected an extract from China, which displayed a certain cytotoxic activity against C. neoformans, due to this extract being cheap and easily available in large amounts. The combination of this kind of propolis with carnosic acid in a 1:4 ratio induced a stronger fungicidal effect, which occurred following a synergistic pattern, without visible alterations in external cell morphology. Furthermore, several carnosic acid-propolis formulations applied onto preformed biofilms decreased the metabolic activity of the sessile cells forming biofilms. These data support the potential application of mixtures containing these two natural extracts in the design of new antifungal strategies in order to combat opportunistic infections caused by prevalent pathogenic fungi.

Novel Bi-Factorial Strategy against Candida albicans Viability Using Carnosic Acid and Propolis: Synergistic Antifungal Action.

The potential fungicidal action of the natural extracts, carnosic acid (obtained from rosemary) and propolis (from honeybees' panels) against the highly prevalent yeast Candida albicans, used herein as an archetype of pathogenic fungi, was tested. The separate addition of carnosic acid and propolis on exponential cultures of the standard SC5314 C. albicans strain caused a moderate degree of cell death at relatively high concentrations. However, the combination of both extracts, especially in a 1:4 ratio, induced a potent synergistic pattern, leading to a drastic reduction in cell survival even at much lower concentrations. The result of a mathematical analysis by isobologram was consistent with synergistic action of the combined extracts rather than a merely additive effect. In turn, the capacity of SC5314 cells to form in vitro biofilms was also impaired by the simultaneous presence of both agents, supporting the potential application of carnosic acid and propolis mixtures in the prevention and treatment of clinical infections as an alternative to antibiotics and other antifungal agents endowed with reduced toxic side effects.

Validation of the SCOFF questionnaire for screening of eating disorders among Mexican university students.

PURPOSE: To evaluate the criterion validity and diagnostic utility of the SCOFF, a brief eating disorder (ED) screening instrument, in a Mexican sample. METHODS: The study was conducted in two phases in 2012. Phase I involved the administration of self-report measures [the SCOFF and the Eating Disorder Inventory-2, (EDI-2)] to 1057 students aged 17-56 years (M age = 21.0, SD = 3.4; 67 % female) from three colleges at the Universidad Autónoma de San Luis Potosí, Mexico. In Phase II, a random subsample of these students (n = 104) participated in the eating disorder examination, a structured interview that yields ED diagnoses. Analyses were conducted to evaluate the SCOFF's criterion validity by examining (a) correlations between scores on the SCOFF and the EDI-2 and (b) the SCOFF's ability to differentiate diagnosed ED cases and non-cases. RESULTS: EDI-2 subscales showed high correlations with the SCOFF scores proving initial evidence of criterion validity. A score of two points on the SCOFF optimized the sensitivity (78 %) and specificity (84 %). With this cutoff, the SCOFF correctly classified over half the cases (PPV = 58 %) and screened out the majority of non-cases (NPV = 93 %) providing further evidence of criterion validity. Analyses were repeated separately for men and women, yielding gender-specific information on the SCOFF's performance. CONCLUSIONS: Taken as a whole, results indicated that the SCOFF can be a useful tool for identifying Mexican university students who are at risk of eating disorders.

Specific stress-induced storage of trehalose, glycerol and D-arabitol in response to oxidative and osmotic stress in Candida albicans.

Candida albicans exponential yeast cells are able to face environmental challenges by mounting a rapid and efficient "general stress response". Here we show that one of the main components of this response consists of the intracellular protective accumulation of the non-reducing disaccharide trehalose and two polyols, glycerol and D-arabitol, an accumulation that occurs in a stress-specific dependent manner. Thus, oxidative exposures promoted a marked increase in both trehalose and D-arabitol in the wild type strain, RM-100, whereas the glycerol content remained virtually unaffected with respect to basal levels. In contrast, osmotic challenges induced the significant storage of glycerol accompanied by minor changes, or even a slight drop, in the intracellular content of trehalose and D-arabitol. We examined the hypothetical role in this process of the MAP kinase Hog1, which regulates the protective responses in C. albicans against both oxidative and osmotic stress. Interestingly, unlike glycerol synthesis, the stress-induced trehalose accumulation was always Hog1-independent, whereas the ability to synthesize D-arabitol was only partially dependent on a functional Hog1 pathway.