Isolation of Candida dubliniensis in denture stomatitis

Objective

To describe the isolation of Candida dubliniensis from a patient with denture stomatitis and to compare with the presence of yeasts in the oral cavities of denture wearers.

Design

One hundred and fifty-two Candida isolates were recovered through oral swabs from denture as well as the underlying mucosa from 100 patients wearing denture. For detection and identification of fungal isolates, standard phenotypic and genotypic methods were used.

Results

Forty-five of 100 denture wearers suffered from denture stomatitis. Seventy-three Candida isolates were recovered from 38 denture wearers without denture stomatitis. In this group, Candida albicans was the predominant species (58.9%), followed by Candida tropicalis (15.1%), Candida guilliermondii (13.7%), Candida glabrata (9.6%), and Candida parapsilosis (2.7%).Seventy-nine isolates were yielded from 40 patients suffering from denture stomatitis. C. albicans was also the most frequently isolated species (58 isolates, 73.4%), followed by C. glabrata and C. tropicalis (7 isolates each, 8.9%), and Saccharomyces cerevisiae (2 isolates, 2.5%). One isolate was yielded of the following species: Candida famata, Candida krusei, C. parapsilosis and C. guilliermondii. Moreover 1 isolate was phenotypic and genotypic identified as C. dubliniensis genotype 1.

Conclusions

C. albicans is the predominant fungal species isolated from denture wearers. C. dubliniensis could be isolated from adults with denture stomatitis.     

Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and vascular permeability which is associated with many pathological processes. 2,5-hydroxybenzene sulfonate (DHBS; dobesilate) is a small molecule with anti-angiogenic activity that has been described as an inhibitor of fibroblast growth factors (FGF). The aim of the present study was to evaluate the effects of DHBS on VEGF-induced actions. The effects of DHBS were evaluated on VEGF-induced proliferation in human umbilical vein endothelial cells (HUVEC) and rat aorta relaxation, as well as on in vivo VEGF-induced skin vascular permeability and neovascularization in rats. DHBS at 50 and 100 μM concentration significantly inhibited the proliferation of HUVEC induced by VEGF (10 ng/ml), without significantly affecting HUVEC proliferation in the absence of VEGF. Rapid VEGF-induced activation of Akt in HUVEC was also prevented by DHBS (100 μM). Additionally, DHBS (2 μM) specifically inhibited the relaxation of rat aorta induced by VEGF (0.1 to 30 ng/ml), but not endothelium-dependent relaxation to acetylcholine (1 nM to 10 μM). The in vivo enhancement of vascular permeability caused by VEGF injection (50 μl at 10 ng/ml) in rat skin was also inhibited by DHBS co-administration (200 μM) (74.8±3.8% inhibition of dye extravasation). Administration of DHBS (200 mg/kg/day; i.p.) also reduced VEGF-induced angiogenesis in vivo. DHBS inhibits main responses elicited in vitro and in vivo by VEGF. As a dual antagonist of VEGF and FGF activities, DHBS could be of therapeutic interest in the treatment of diseases related to VEGF/FGF overproduction and excessive angiogenesis.     

Gastroprotective effect and cytotoxicity of carnosic acid derivatives

Carnosic acid (CA) is the main phenolic diterpene of rosemary (Rosmarinus officinalis L., Lamiaceae) and presents gastroprotective effect in vitro and in vivo. To determine structure-activity relationships, seventeen esters and ethers of CA were prepared, comprising aliphatic, aromatic, and heterocyclic compounds. The naturally occurring 12-O-methylcarnosic acid (14) was also included in the study. The compounds were evaluated for their gastroprotective activity in the HCl/EtOH-induced gastric lesions model in mice, and for cytotoxicity in human adenocarcinoma AGS cells, Hep G2 hepatocellular carcinoma cells, and human lung fibroblasts. At 10 mg/kg, some of the CA derivatives (5, 8, 9, 12, 14, and 18) were more effective preventing gastric lesions than the reference compound lansoprazole at the same dose. The dibenzoate 9, diindoleacetate 12, and the derivative 18 showed the best gastroprotective effect combined with the lowest cytotoxicity.     

Antivenoms for snakebite envenomings

Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. Antivenoms are manufactured by immunizing animals, usually horses, with venoms from a single or several medically-relevant snake species. Antivenoms are constituted by either whole IgG molecules or the immunoglobulin fragments F(ab')? and Fab, obtained by digestion with pepsin and papain, respectively. Differences in the pharmacokinetics of these active substances have pharmacodynamic implications. Novel technological possibilities may improve the quality of antivenoms in the future, as well as their microbial safety. Antivenom administration might induce early and late adverse reactions, whose possible mechanisms are discussed. Owing to the large variety in the composition of snake venoms and to the need to demonstrate neutralization of relevant snake venoms in different countries, a meticulous preclinical and clinical assessment of antivenom efficacy and safety is required before an antivenom is introduced into clinical application. The accessibility of antivenoms in low-income tropical countries is of concern and efforts should be directed at guaranteeing the access of safe and effective antivenoms at affordable prices and their correct clinical use in these countries.     

Partially ordered sets: ranking and prediction of substances' properties

There are at least two significant applications of partial order theory in chemistry: Ranking methods and substances' properties prediction. In both cases, a set of objects is endowed with a partial order relation e.g. "more polluting than", "can be obtained from", "more reactive than" etc. The couple of set and partial order relation is known in mathematics as a partially ordered set (poset). Ranking methods, such as the Hasse diagram technique, lead to a partial order where several incomparabilities (lack of order) appear between pairs of objects. This phenomenon is quite common in ranking studies, and it often is circumvented by a combination of object features leading to a total order. However, such a combination introduces subjectivities and bias in the ranking process. Here a step-by-step procedure is shown to turn incomparabilities into comparabilities taking into account all the possible bias by a linear combination of features. In such a manner, it is possible to predict how probable it is to obtain a particular total order from a given poset. Similarly, it is possible to calculate the needed bias over certain attributes to obtain a particular total order. An example application is shown where substances are ranked according to their bioconcentration factor and biodegradation potential. Another application of partial order theory to chemistry has to do with the prediction of properties for a set of substances related in a (preferably systematic) chemical fashion. A customary relation is "can be obtained from"; if such a relation is set up for a given molecular structure e.g. benzene, and all its substituted derivatives (say chlorinated ones) are considered, then the set of benzene and its chlorinated derivatives are partially ordered. Taking advantage of the poset generated, different methods can be applied to predict properties of the substances considered in the poset. Such methods include the poset-average, cluster expansion, and splinoid methods. In this paper we discuss each one of these methods, its advantages and disadvantages and we outline its applicability to estimate cooperative free energies of hemoglobins with different degree of oxygenation.