Impact of active efflux in the development of MDR phenotypes in Staphylococcus aureus

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Functionalisation of terpenoids at C-4 via organopalladium dimers: cyclopropane formation during oxidation of homoallylic sigma-organopalladium intermediates with lead tetraacetate

The synthesis of new potential adjuvant saponin aglycons was investigated by selective palladium mediated C-H functionalisation of appropriately functionalised derivatives of lanosterol, cholesterol, and friedelin. The desired equatorial aldehyde functionality was successfully introduced into the lanosterol skeleton as expected. Cyclopalladation of a cholesterol derivative proceeded as expected, but during oxidation of the organopalladium intermediate, participation of the adjacent alkene functionality led to stereoselective formation of a cyclopropane and introduction of an acetate group into the steroid backbone at C-6. Further investigation of this unusual cyclopropane formation on a model decalin system confirmed the result, but C-H activation on a related open chain system was prevented by complexation of the alkene functionality to the palladium. (c) 2007 Elsevier Ltd. All rights reserved

Multidrug efflux pumps in Staphylococcus aureus: an update.

The emergence of infections caused by multi- or pan-resistant bacteria in the hospital or in the community settings is an increasing health concern. Albeit there is no single resistance mechanism behind multiresistance, multidrug efflux pumps, proteins that cells use to detoxify from noxious compounds, seem to play a key role in the emergence of these multidrug resistant (MDR) bacteria. During the last decades, experimental data has established their contribution to low level resistance to antimicrobials in bacteria and their potential role in the appearance of MDR phenotypes, by the extrusion of multiple, unrelated compounds. Recent studies suggest that efflux pumps may be used by the cell as a first-line defense mechanism, avoiding the drug to reach lethal concentrations, until a stable, more efficient alteration occurs, that allows survival in the presence of that agent. In this paper we review the current knowledge on MDR efflux pumps and their intricate regulatory network in Staphylococcus aureus, a major pathogen, responsible from mild to life-threatening infections. Particular emphasis will be given to the potential role that S. aureus MDR efflux pumps, either chromosomal or plasmid-encoded, have on resistance towards different antimicrobial agents and on the selection of drug - resistant strains. We will also discuss the many questions that still remain on the role of each specific efflux pump and the need to establish appropriate methodological approaches to address all these questions.publishersversionpublishe

Correlators of Vertex Operators for Circular Strings with Winding Numbers in AdS5xS5

We compute semiclassically the two-point correlator of the marginal vertex operators describing the rigid circular spinning string state with one large spin and one windining number in AdS_5 and three large spins and three winding numbers in S^5. The marginality condition and the conformal invariant expression for the two-point correlator obtained by using an appropriate vertex operator are shown to be associated with the diagonal and off-diagonal Virasoro constraints respectively. We evaluate semiclassically the three-point correlator of two heavy circular string vertex operators and one zero-momentum dilaton vertex operator and discuss its relation with the derivative of the dimension of the heavy circular string state with respect to the string tension.Comment: 16 pages, LaTeX, no figure

Virulence potential of biofilm producing Staphylococcus pseudintermedius, Staphylococcus aureus and Staphylococcus coagulans causing skin infections in companion animals

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Characterization of antimicrobial resistance in Staphylococcus epidermidis colonizing veterinary staff and students

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Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells

Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n = 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery. (c) 2023, The Author(s)

Mineralocorticoid receptor antagonists eplerenone and spironolactone modify adrenal cortex morphology and physiology

Mineralocorticoid receptor antagonists (MRAs) are a class of anti-hypertensive drugs that act by blocking aldosterone action. The aim of this study was to evaluate whether the MRAs spironolactone and eplerenone influence adrenal cortical physiology and morphology. Spontaneous hypertensive rats (SHR, n = 18) and normotensive rats (WKY, n = 18) were randomly exposed to a daily dose of spironolactone (n = 6), eplerenone (n = 6), or no drug (n = 6) over 28 days. After that, aldosterone, corticosterone, and 11-deoxycorticosterone plasma concentrations were quantified. Adrenal glands were subjected to morphological analysis to assess lipid droplets content, capsular width, cell proliferation, and steroidogenic proteins expression. The adrenal cortex in untreated SHR showed higher lipid droplet content as than in WKY. In SHR, MRA treatment was associated with higher circulating aldosterone levels and Ki-67 expression in aldosterone-secreting cells. In WKY, the only difference observed after MRA spironolactone treatment was a narrower capsule. There was no difference in abundance of steroidogenic enzyme between groups. In conclusion, MRAs modify adrenal gland function and morphology in SHR. The effects observed within the adrenal glomerulosa with aldosterone-secreting cell proliferation and higher circulating aldosterone levels suggests that MRA treatment provokes activation of the renin angiotensin system. The prognostic value of hyperaldosteronism secondary to MRAs blockade requires further investigation.Funding: This research was funded by the Associação dos Amigos do Serviço de Endocrinologia do Hospital de São João (2020–2021). Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT)-Portugal (UIDB/00215/2020 and UIDP/00215/2020—approval date: 2019)

Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 +/- 0.58 kg/m(2)) or class 3 (n = 8; BMI 47.79 +/- 1.52 kg/m(2)) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment

Constructing Lifshitz solutions from AdS

Under general assumptions, we show that a gravitational theory in d+1 dimensions admitting an AdS solution can be reduced to a d-dimensional theory containing a Lifshitz solution with dynamical exponent z=2. Working in a d=4, N=2 supergravity setup, we prove that if the AdS background is N=2 supersymmetric, then the Lifshitz geometry preserves 1/4 of the supercharges, and we construct the corresponding Killing spinors. We illustrate these results in examples from supersymmetric consistent truncations of type IIB supergravity, enhancing the class of known 4-dimensional Lifshitz solutions of string theory. As a byproduct, we find a new AdS4 x S1 x T(1,1) solution of type IIB.Comment: 29 pages, no figures; v2 minor corrections, a reference adde