Sensibilidad de aislamientos de Candida albicans de hemocultivos a 3 fármacos: estudio retrospectivo en Rio Grande do Sul,Brasil, 1999 a 2009

BackgroundCandidiasis is one of the most important among recurrent invasive yeast infections in patients, thus antifungal treatment becomes a challenge.AimsThe aim of this study was to evaluate the in vitro activity of clinical Candida albicans isolates from blood cultures to fluconazole, amphotericin B and anidulafungin, in a hospital from Rio Grande do Sul, Brazil.MethodsThe susceptibility of 153 isolates to the 3 drugs mentioned was tested according to Clinical and Laboratory Standars Institute. Minimal inhibitory and fungicidal concentrations (MIC, MFC, respectively) of each drug were determined, as well as the epidemiological cutoff value (ECV).ResultsAll of the isolates were susceptible to anidulafungin, MIC and MFC ≤ 1 μg/ml; however, when compared with ECV, 3% of the isolates exhibited higher values against fluconazole, 96% were susceptible, 3% susceptible dose-dependent, and 1% resistant. Also, it was observed that 21% of the isolates exhibited higher values than ECV. One isolate was resistant to amphotericin B; the other ones, susceptible, based on the MFC; furthermore, 1.5% of the isolates exhibited higher values.ConclusionsC. albicans isolates exhibited more susceptibility to anidulafungin, and 90% of them (MIC₉₀) exhibited the lowest values against amphotericin B. Based on ECV and Pfaller classification, isolates could be resistant to fluconazole, demonstrating the importance of the combination of these parameters.     

Analytical and numerical analysis of human dental occlusal contact

The knowledge of contact forces in teeth surfaces during mastication or para-functional movements can help to understand processes related to friction and wear of human dental enamel. The development of a numerical model for analysis of the occlusal contact between two antagonistic teeth is proposed, which includes three basic steps: the characterisation of the surface roughness, its homogenisation using an assumed distribution function and the numerical determination of the resulting forces. Finite element strain results for the main different asperities are statistically combined, deriving the predicted macroscopic behaviour of the interface. Axisymmetric and 3D numerical models with an elasto-plastic constitutive law are used to simulate micro-indentations and micro-contacts, respectively. The contact is allowed to occur locally in planes not necessarily parallel to the surface's mean plane, a problem for which there is no analytical solution. The three identified parameters, homogenised surface hardness (3.68 GPa), surface yield stress (3.08 GPa) and static friction coefficient (0.23), agree with the experimental values reported in the literature.     

Unrooted trees discovered independently in philology and phylogenetics: a remarkable case of methodological convergence

We report on the only known case of independent discovery of unrooted trees in a historical science outside of biological systematics. The method of textual criticism (ecdotics, i.e., the building of text-version genealogies) created by French philologist Henri Quentin (1872–1935) proposes the use of a type of branching scheme equivalent to unrooted trees in phylogenetics. Because Quentin's method has never become the prevailing paradigm in philology, his insight into unrooted trees has not been noticed in previous studies comparing philology and phylogenetics. In fact, the modern use of unrooted trees in philology is seen as imported from phylogenetics. Quentin's procedure starts by building an unrooted tree (‘chain’) expressing the network of text versions (taxa) based on ‘variants’ (equivalent to unpolarized character states). Such undirected scheme is then rooted on the basis of extrinsic temporal information, thus resulting in a complete (rooted) hypothesis of relationships. Quentin asserts that the building of an unrooted tree precedes the determination of its orientation (rooting) and that the two procedures reflect distinct levels of structural organization, relying on different assumptions. Henri Quentin fully grasped the implications of time-reversible properties of unrooted trees and associated characters, in striking prescience of the same concepts developed in phylogenetics some 45 years later. The two versions of unrooted trees were developed entirely independently of each other and such convergence is testimony to the formal efficiency of approaching historical reconstruction in unrooted and rooted dimensions.     

Deletion of P399_E401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399_E401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant POR proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399_E401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17α-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399_E401 revealed reduced stability and flexibility of the mutant. In conclusion, P399_E401del is a novel mutation in POR that provides valuable genotype–phenotype and structure–function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399_E401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.     

Climate, history and neutrality as drivers of mammal beta diversity in Europe: insights from multiscale deconstruction

1.?Environmental sorting, historical factors and neutral dynamics may all drive beta diversity (change in species composition across space), but their relative importance remains unresolved. In the case of European mammals, key potential drivers of large-scale beta diversity include current climate, neutral dynamics and two historical factors: Pleistocene glaciations and peninsular dynamics (immigration from extra-regional eastern faunal source areas and inter-linked relictual survival and evolutionary differentiation in isolated areas). 2.?We assessed the relative importance of these drivers using a novel analytical framework to deconstruct beta diversity of non-volant mammals in Europe (138 species) into its turnover (change in species composition because of species replacements) and nestedness components (change in species composition because of species richness differences) at continental and regional (250,000 km(2) ) scales. 3.?We found continental-scale mammal beta diversity to be mainly caused by spatial turnover (99·9%), with only a small contribution (0·1%) from nestedness. 4.?Current climate emerged as an important driver of beta diversity, given the strong continental-scale turnover, particularly in north-south direction, i.e., in line with the latitudinal climate gradient, and, more directly, the strong correlation of climate with spatial turnover at both continental and regional scales. 5.?However, there was also evidence for the importance of non-climatic drivers. Notably, the compositional variation purely accounted for by space was greater than that purely accounted for by environment for both the turnover and the nestedness component of beta diversity. Furthermore, the strong longitudinal turnover within Southern Europe is in accordance with the region's long-term climatic stability having allowed multiple refugia and local evolutionary diversification. As expected from peninsular dynamics, there was increasing dissimilarity with geographic distance in an east-west direction because of nestedness, but only in Central and Northern Europe. 6.?In conclusion, European mammal beta diversity mainly reflects spatial turnover and only to a limited extent nestedness and is driven by current climate in combination with historical - and perhaps, neutral - dynamics. These findings suggest that a key challenge for climate-change predictive studies will be taking the influence of non-climatic factors into account.     

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10 mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β₁ (TGF-β₁) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β₁, as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β₁ and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.     

Outbreak of human herpesvirus type 1 infection in nonhuman primates (Callithrix penincillata)

Human herpesvirus type 1 (HHV-1) is widely dispersed among the human population. Although infection is often asymptomatic in humans, nonhuman primates develop a severe and often fatal infection. In August 2006, 13 black-tufted marmosets (Callithrix penincillata) from a group of 14 presented with clinical apathy, anorexia, and ataxia. Physical examination revealed conjunctivitis, erosive or ulcerative lesions on the skin, and swollen lymph nodes. Of the 14 animals captured, 10 died. Grossly, ulcers and erosions were observed on the skin of face, nasal planum, lips, and oral mucosa. Histologically, superficial vesicular and erosive stomatitis with associated basophilic intranuclear inclusion bodies in the squamous epithelium were observed. Swabs from oral lesions and tissue samples from necropsied animals were positive for HHV-1 by nested polymerase chain reaction for eight animals.     

Schistosoma mansoni: a method for inducing resistance to praziquantel using infected Biomphalaria glabrata snails

To elucidate the mechanisms of antischistosoma resistance, drug-resistant Schistosoma mansoni laboratory isolates are essential. We developed a new method for inducing resistance to praziquantel (PZQ) using successive drug treatments of Biomphalaria glabrata snails infected with S. mansoni. Infected B. glabrata were treated three times with 100 mg/kg PZQ for five consecutive days with a one-week interval between them. After the treatment, the cercariae (LE-PZQ) produced from these snails and the LE strains (susceptible) were used to infect mice. Forty-five days after infection, mice were treated with 200, 400 or 800 mg/kg PZQ. Thirty days post-treatment, we observed that the mean number of worms recovered by perfusion was significantly higher in the group of mice infected with the LE-PZQ isolate treated with 200 and 400 mg/kg in comparison to the LE strain with the same treatment. Moreover, there was a significant difference between the ED50 (effective dose required to kill 50% of the worms) of the LE-PZQ isolate (362 mg/kg) and the LE strain (68 mg/kg). In the in vitro assays, the worms of the LE-PZQ isolate were also less susceptible to PZQ. Thus, the use of infected snails as an experimental model for development of resistance to S. mansoni is effective, fast, simple and cheap.