In vitro activities of natural products against oral Candida isolates from denture wearers

Background: Candida-associated denture stomatitis is a frequent infectious disease. Treatment of this oral condition is difficult because failures and recurrences are common. The aim of this study was to test the in vitro antifungal activity of pure constituents of essentials oils. -- Methods: Eight terpenic derivatives (carvacrol, farnesol, geraniol, linalool, menthol, menthone, terpinen-4-ol, and aterpineol), a phenylpropanoid (eugenol), a phenethyl alcohol (tyrosol) and fluconazole were evaluated against 38 Candida isolated from denture-wearers and 10 collection Candida strains by the CLSI M27-A3 broth microdilution method. -- Results: Almost all the tested compounds showed antifungal activity with MIC ranges of 0.03-0.25% for eugenol and linalool, 0.03-0.12% for geraniol, 0.06-0.5% for menthol, a-terpineol and terpinen-4-ol, 0.03-0.5% for carvacrol, and 0.06-4% for menthone. These compounds, with the exception of farnesol, menthone and tyrosol, showed important in vitro activities against the fluconazole-resistant and susceptible-dose dependent Candida isolates. -- Conclusions: Carvacrol, eugenol, geraniol, linalool and terpinen-4-ol were very active in vitro against oral Candida isolates. Their fungistatic and fungicidal activities might convert them into promising alternatives for the topic treatment of oral candidiasis and denture stomatitis.

Robust Sliding Control of SEIR Epidemic Models

This paper is aimed at designing a robust vaccination strategy capable of eradicating an infectious disease from a population regardless of the potential uncertainty in the parameters defining the disease. For this purpose, a control theoretic approach based on a sliding-mode control law is used. Initially, the controller is designed assuming certain knowledge of an upper-bound of the uncertainty signal. Afterwards, this condition is removed while an adaptive sliding control system is designed. The closed-loop properties are proved mathematically in the nonadaptive and adaptive cases. Furthermore, the usual sign function appearing in the sliding-mode control is substituted by the saturation function in order to prevent chattering. In addition, the properties achieved by the closed-loop system under this variation are also stated and proved analytically. The closed-loop system is able to attain the control objective regardless of the parametric uncertainties of the model and the lack of a priori knowledge on the system.

Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells

Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

Celiac disease in the Mediterranean area

Background: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. Methods: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. Results: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. Conclusions: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines.

Celiac disease in the Mediterranean area

Background: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. Methods: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. Results: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. Conclusions: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines.