Gymnemic acids inhibit hyphal growth and virulence in Candida albicans

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine

Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease

AIMS: The diastolic pulmonary pressure gradient (DPG) has recently been introduced as a specific marker of combined pre-capillary pulmonary hypertension (Cpc-PH) in left heart disease (LHD). However, its diagnostic and prognostic superiority compared with traditional haemodynamic indices has been challenged lately. Current recommendations explicitly denote that in the normal heart, DPG values are greater than zero, with DPG >/=7 mmHg indicating Cpc-PH. However, clinicians are perplexed by the frequent observation of DPG 0.05). Patients with large V-waves had negative and lower DPG than those without augmented V-waves (P 0.05). Positive, but normal DPG (0-6 mmHg) carried a worse 2-year prognosis for death and/or heart transplantation than DPGNEG (hazard ratio 2.97; P < 0.05). CONCLUSION: Our results advocate against DPGNEG constituting a measurement error. We propose that DPGNEG can partially be ascribed to large V-waves and carries a better prognosis than DPG within the normal positive range

Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay

Υποθέσεις κρίσεων του Ορθόδοξου Κλήρου στην Ενετοκρατούμενη Κρήτη

Με γνώμονα έγγραφο, με χρονολογία 29 Οκτωβρίου 1604, από τον κώδικα με αριθμό 20 της Καθολικής Αρχιεπισκοπής Κρήτης, που βρίσκεται σήμερα στο αρχείο της Καθολικής Αρχιεπισκοπής Τήνου, δια του οποίου επιβάλλεται ποινή στον ορθόδοξο κληρικό Απόστολο Γιαλινά της ενορίας Αγίας Ειρήνης του χωρίου Κατσαμπά περιοχής Χάνδακα, επειδή τέλεσε γάμο χωρίς την κατάλληλη εκκλησιαστική άδεια και ενάντια στον κανόνα της Συνόδου του Τριδέντου, επιχειρούμε να μελετήσουμε την λειτουργία της Ενετικής Εκκλησιαστικής Διοικήσεως στην Κρήτη, τις σχέσεις της με την Ορθόδοξη Εκκλησία αλλά και τον τρόπο με τον οποίο αντιμετώπιζε και έκρινε υποθέσεις που αφορούσαν την δεύτερη.Based on a document dated 29 October 1604, from Canon Law code no. 20 of the Catholic Archdiocese of Crete, which is available nowadays in the archives of the Catholic Archdiocese of Tinos, for which a penalty is imposed on the Orthodox cleric Apostolos Gialinas of the parish of Saint Irene in the village of Katsamba, Heraklion region, because he took a wedding without the appropriate church permission and against the decrees of the Council of Trent. We attempt to study the functioning of the Venetian Ecclesiastical Administration in Crete, its relations with the Orthodox Church and the manner in which it handled and reached decisions concerning the latter

On the Value of Emerging, Day-Ahead Market Related Wind-Storage Narratives in Greece: An Early Empirical Analysis

Large-scale integration of renewable energy sources introduces high levels of uncertainty in power systems. In addressing the inherent uncertainty of renewables, coupling with energy storage systems allows for improved dispatchability, not only in terms of power system integration but also in terms of market participation. To that end, we currently look into the coupling of wind energy and energy storage and assess the ex-post value of different, day-ahead market related wind–storage narratives. In doing so, we apply practical dispatch strategies using empirical market signals, vary the size of storage, and adopt different cycling patterns, treating the configurations examined as price-taker units. In addition, by integrating different wind regimes and several years of spot price series, we argue that our approach captures different spatial and temporal characteristics; thus, offering a broad, representative view of the value and associated risk of similar market scenarios in the study area of Greece