Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons.

BACKGROUND. Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. DESIGN. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs).The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. RESULTS. The baseline levels of uric acid were higher in the MFT group.Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004).In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03),and the FEUA was higher (P = 0.04).The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03).In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). CONCLUSIONS. Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy.The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans.

OBJECTIVE: To evaluate the effect of a 4-day carbohydrate overfeeding on whole body net de novo lipogenesis and on markers of de novo lipogenesis in subcutaneous adipose tissue of healthy lean humans. RESEARCH METHODS AND PROCEDURES: Nine healthy lean volunteers (five men and four women) were studied after 4 days of either isocaloric feeding or carbohydrate overfeeding. On each occasion, they underwent a metabolic study during which their energy expenditure and net substrate oxidation rates (indirect calorimetry), and the fractional activity of the pentose-phosphate pathway in subcutaneous adipose tissue (subcutaneous microdialysis with 1,6(13)C2,6,6(2)H2 glucose) were assessed before and after administration of glucose. Adipose tissue biopsies were obtained at the end of the experiments to monitor mRNAs of key lipogenic enzymes. RESULTS: Carbohydrate overfeeding increased basal and postglucose energy expenditure and net carbohydrate oxidation. Whole body net de novo lipogenesis after glucose loading was markedly increased at the expense of glycogen synthesis. Carbohydrate overfeeding also increased mRNA levels for the key lipogenic enzymes sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase. The fractional activity of adipose tissue pentose-phosphate pathway was 17% to 22% and was not altered by carbohydrate overfeeding. DISCUSSION: Carbohydrate overfeeding markedly increased net de novo lipogenesis at the expense of glycogen synthesis. An increase in mRNAs coding for key lipogenic enzymes suggests that de novo lipogenesis occurred, at least in part, in adipose tissue. The pentose-phosphate pathway is active in adipose tissue of healthy humans, consistent with an active role of this tissue in de novo lipogenesis.

Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure.

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.

L'aportació de Tomàs Cerdà en la introducció del càlcul diferencial i integral a l'Espanya del segle XVIII

El desenvolupament del càlcul diferencial i integral com a disciplina científica a Europa durant el segle XVIII no és un tema nou. Però s’ha acostumat a enfocar la visió d’aquesta formació molt sovint des del “centre” i a partir de les grans figures com Isaac Newton o Gottfried Wilhelm Leibniz. En el present treball el protagonista potser, per a molts, no és una figura de primera línia; Tomàs Cerdà, és un ensenyant a Barcelona i a Madrid durant la segona meitat del segle XVIII, que “tradueix” al castellà autors anglesos, però que amb la seva pràctica està realment introduint el nou càlcul a Espanya i donant, de fet, una orientació d’aquesta nova disciplina als seus deixebles. El com i per què Cerdà decideix quin serà el seu guia en la introducció del càlcul diferencial i integral i quines seran les seves pròpies aportacions en aquesta labor seran els temes centrals del nostre treball. La nostra tasca ha anat, així doncs, a entendre millor, el procés de divulgació del coneixement científic, veient-lo en tot moment com formant part activa del mateix procés de construcció d’aquest coneixement.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

La revascularisation transmyocardique au laser--un risque potentiel en condition aiguë [Laser transmyocardial revascularization--a potential risk in an acute situation?]

Morphological and functional effects of transmyocardial laser revascularization (TMLR) are analyzed in an acute setting on a porcine model. Ten channels were drilled in the left lateral wall of the heart of 15 pigs (mean weight, 73 +/- 4 kg) with a Holmium-YAG laser (wavelength: 2.1 mu, probe diameter: 1.75 mm). Echocardiographic control was performed before the TMLR procedure as well as 5 min and 30 min thereafter. Echocardiographic parameters were recorded in short-axis at the level of the laser channels, and included left ventricular ejection fraction, fractional shortening and segmental wall motility of the channels' area (scale 0-3: 0 = normal, 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). After sacrifice the lased region was sliced perpendicularly to the channels for histological and morphometrical analysis. Five minutes after the drilling of the channels, all the echocardiographic index worsened significantly in comparison with baseline values (p < 0.01). All recovered after 30 min and showed no difference with baseline values. Cross-section of the channel lesions measured 8.8 +/- 2.4 mm2 which is more than three times that of the probe (p < 0.01). In acute conditions, the lesions due to the TMLR probe are significantly larger than the probe itself and cause a transient drop of the segmental wall motility on a healthy myocardium. These results suggest that TMLR should be used cautiously in the clinical setting for patients with an impaired ventricular function.

A non-invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man.

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55% carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50% of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 +/- 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 +/- 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Textural, chemical, and isotopic effects of late-magmatic carbonatitic fluids in the carbonatite-syenite Tamazeght complex, High Atlas Mountains, Morocco

Carbonatites of the Eocene Tamazeght complex, High Atlas Mountains, Morocco, consist of calciocarbonatites (alvikite and sovite dykes) and magnesiocarbonatites (diatreme breccias and dykes rocks). These are associated with ultramafic, shonkinitic, gabbroic to monzonitic and various foid syenitic silicate units. Stable and radiogenic isotope compositions for carbonatites and silicate rocks indicate that they share a common source in the mantle, although for some carbonatitic samples contamination with sedimentary rocks seems important. The observed isotopic heterogeneity is mainly attributed to source characteristics, fractional crystallization (accompanied by various degrees of assimilation), and late- to post-magmatic fluid-rock interaction. During the late fluid-rock interaction, Sr, Mn, and possibly also Fe were mobilized and redistributed to form secondary carbonate minerals in carbonatites. These fluids also penetrated into the adjacent syenitic rocks, causing enrichment in the same elements.

Select-divide-and-conquer method for large-scale configuration interaction

A select-divide-and-conquer variational method to approximate configuration interaction (CI) is presented. Given an orthonormal set made up of occupied orbitals (Hartree-Fock or similar) and suitable correlation orbitals (natural or localized orbitals), a large N-electron target space S is split into subspaces S0,S1,S2,...,SR. S0, of dimension d0, contains all configurations K with attributes (energy contributions, etc.) above thresholds T0={T0egy, T0etc.}; the CI coefficients in S0 remain always free to vary. S1 accommodates KS with attributes above T1≤T0. An eigenproblem of dimension d0+d1 for S0+S 1 is solved first, after which the last d1 rows and columns are contracted into a single row and column, thus freezing the last d1 CI coefficients hereinafter. The process is repeated with successive Sj(j≥2) chosen so that corresponding CI matrices fit random access memory (RAM). Davidson's eigensolver is used R times. The final energy eigenvalue (lowest or excited one) is always above the corresponding exact eigenvalue in S. Threshold values {Tj;j=0, 1, 2,...,R} regulate accuracy; for large-dimensional S, high accuracy requires S 0+S1 to be solved outside RAM. From there on, however, usually a few Davidson iterations in RAM are needed for each step, so that Hamiltonian matrix-element evaluation becomes rate determining. One μhartree accuracy is achieved for an eigenproblem of order 24 × 106, involving 1.2 × 1012 nonzero matrix elements, and 8.4×109 Slater determinants

Variational calculation of static and dynamic vibrational nonlinear optical properties

The vibrational configuration interaction method used to obtain static vibrational (hyper)polarizabilities is extended to dynamic nonlinear optical properties in the infinite optical frequency approximation. Illustrative calculations are carried out on H2 O and N H3. The former molecule is weakly anharmonic while the latter contains a strongly anharmonic umbrella mode. The effect on vibrational (hyper)polarizabilities due to various truncations of the potential energy and property surfaces involved in the calculation are examined

Variational calculation of vibrational linear and nonlinear optical properties

A variational approach for reliably calculating vibrational linear and nonlinear optical properties of molecules with large electrical and/or mechanical anharmonicity is introduced. This approach utilizes a self-consistent solution of the vibrational Schrödinger equation for the complete field-dependent potential-energy surface and, then, adds higher-level vibrational correlation corrections as desired. An initial application is made to static properties for three molecules of widely varying anharmonicity using the lowest-level vibrational correlation treatment (i.e., vibrational Møller-Plesset perturbation theory). Our results indicate when the conventional Bishop-Kirtman perturbation method can be expected to break down and when high-level vibrational correlation methods are likely to be required. Future improvements and extensions are discussed

Basis set and electron correlation effects on initial convergence for vibrational nonlinear optical properties of conjugated organic molecules

The level of ab initio theory which is necessary to compute reliable values for the static and dynamic (hyper)polarizabilities of three medium size π-conjugated organic nonlinear optical (NLO) molecules is investigated. With the employment of field-induced coordinates in combination with a finite field procedure, the calculations were made possible. It is stated that to obtain reasonable values for the various individual contributions to the (hyper)polarizability, it is necessary to include electron correlation. Based on the results, the convergence of the usual perturbation treatment for vibrational anharmonicity was examined

A fractionally integrated approach to monetary policy and inflation dynamics

This paper relaxes the standard I(0) and I(1) assumptions typically stated in the monetary VAR literature by considering a richer framework that encompasses the previous two processes as well as other fractionally integrated possibilities. First, a timevarying multivariate spectrum is estimated for post WWII US data. Then, a structural fractionally integrated VAR (VARFIMA) is fitted to each of the resulting time dependent spectra. In this way, both the coefficients of the VAR and the innovation variances are allowed to evolve freely. The model is employed to analyze inflation persistence and to evaluate the stance of US monetary policy. Our findings indicate a strong decline in the innovation variances during the great disinflation, consistent with the view that the good performance of the economy during the 80’s and 90’s is in part a tale of good luck. However, we also find evidence of a decline in inflation persistence together with a stronger monetary response to inflation during the same period. This last result suggests that the Fed may still play a role in accounting for the observed differences in the US inflation history. Finally, we conclude that previous evidence against drifting coefficients could be an artifact of parameter restriction towards the stationary region. Keywords: monetary policy, inflation persistence, fractional integration, timevarying coefficients, VARFIMA. JEL Classification: E52, C32

Plataforma e-commerce Magento, millora de la importació massiva de productes

Aquest projecte tracta de la millora de l’actual sistema d’importació que disposa Magento. Actualment per importar els productes a una botiga Magento es necessita treballar amb un fitxer csv on s’introdueix una gran quantitat de dades i requereix una gran quantitat de temps i esforç per part de l’empresa. Per millorar l’actual sistema, es proposa crear una integració entre Magento i Google Docs, fent que tots els productes que es vulguin importar s’introdueixin en un full de càlcul Google Docs i s’importin a la botiga Magento.