Calorimetric and spectroscopic studies characterization of newborn rat’ blood serum after maternal administration of cyclophosphamide

Differential scanning microcalorimetry (DSC) and UV–VIS absorption spectroscopy were used to obtain the characteristics of blood serum from newborn rat’ after maternal treatment with cyclophosphamide in comparison with control. The obtained DSC curves reveal a complex endothermic peak due to the unfolding process of various serum proteins. Thermal profiles and absorption spectra of blood serum are sensitive to the age of newborns as well as to effect of maternal administration of cyclophosphamide. The most significant disturbances in serum proteome were observed for 14-day old newborns. The thermodynamic parameters: enthalpy change (DH), the normalized first moment (M1) of the thermal transition with respect to the temperature axis and the ratio of Cp ex at 70 and 60 C describing denaturation contributions of globulin forms in respect to unliganded albumin with haptoglobin was estimated. Moreover, the second derivative spectroscopy in the UV region was used to resolve the complex protein spectrum. The differences in blood serum detected by DSC and UV–VIS confirm a potential usefulness of these methods for diagnostic and monitoring changes with age as well as the pathological state of blood serum

EFFECT OF LOW-DOSE TACROLIMUS COADMINISTERED WITH RALOXIFENE ON THE SKELETAL SYSTEM IN MALE RATS

Polish Pharmaceutical Society Tacrolimus, a calcineurin inhibitor, is used as an immunosuppressive drug to prevent organ transplant rejection. Numerous clinical and experimental reports indicate that administration of immunosuppressants leads to development of osteopenia (1-3). Experimental osteopenia induced by calcineurin inhibitors (cyclosporin and tacrolimus) has been reported to be associated with high bone turnover (3). They accelerate bone remodeling, and net bone loss is caused by bone resorption prevailing over bone formation. However, there are also reports demonstrating bone formation inducing effect of tacrolimus in experimental models. Tacrolimus induced bone formation in demineralized bone matrix implants (isogeneic and xenogeneic) and in implants containing bone marrow cells (allografts and isografts) The aim of the present study was to investigate whether low-dose tacrolimus (0.3 mg/kg po daily for 4 weeks) affects bone mineralization and bone Immunosuppresants are known to unfavorably affect the osseous system. However, in our previous study on bone histomorphometric parameters we observed that low-dose tacrolimus intensified bone formation. The aim of the present study was to investigate the effects of low-dose tacrolimus on bone mechanical properties and mineralization in male rats. The effects of concurrent administration of tacrolimus and raloxifene were also studied. Raloxifene is a selective estrogen receptor modulator, used in the prevention and treatment of postmenopausal osteoporosis. In male rats raloxifene induces moderate intensification of bone mineralization. The experiments were carried out on mature male Wistar rats. The animals were divided into four groups (n = 7): control rats, rats treated with tacrolimus (0.3 mg/kg po), rats treated with raloxifene hydrochloride (5 mg/kg po) and rats treated with tacrolimus and raloxifene hydrochloride concurrently at abovementioned doses. The drugs were administered daily for 4 weeks. Body mass, bone mass and bone mineral content in the tibia, femur and L-4 vertebra, as well as mechanical properties of the whole femur (extrinsic stiffness, ultimate and breaking load, deformation caused by the applied load) and the femoral neck (load at fracture) were examined. Administration of tacrolimus at a dose of 0.3 mg/kg po for 4 weeks did not affect bone mechanical properties and mineralization. Concurrent administration of tacrolimus and raloxifene resulted in changes similar to those caused by raloxifene alone (statistically significant increases in the bone mass/body mass ratio, bone mineral content/body mass ratio and bone mineral content/bone mass ratio in comparison with the control rats, and no effect on bone mechanical properties). Results of the present study do not support the hypothesis that tacrolimus may be useful as a drug stimulating bone formation in skeletal diseases. mechanical properties in male rats. The effects of concurrent administration of tacrolimus and raloxifene on the sketetal system of male rats were also studied. Raloxifene is a selective estrogen receptor modulator, used in the prevention and treatment of postmenopausal osteoporosis. Raloxifene has been also considered as a potential drug used in osteoporosis in men. Here we used raloxifene as a reference drug inducing moderate intensification of bone mineralization in male rats (8). PHARMACOLOGY EFFECT OF LOW-DOSE TACROLIMUS Keywords EXPERIMENTAL The experiments were carried out on mature male Wistar rats (body mass at the beginning of the experiment: 250ñ300 g), fed a standard diet ad libitum. The rats were obtained from the Center of Experimental Medicine, Medical University of Silesia. The procedure of the experiments on animals was approved by the Ethical Commission, Katowice. The animals were divided into four groups (n = 7): I ñ control rats; II ñ rats treated with tacrolimus (Prograf, Fujisawa, 0.3 mg/kg po); III ñ rats treated with raloxifene hydrochloride (Evista, Eli Lilly, 5 mg/kg po); IV ñ rats treated with tacrolimus (0.3 mg/kg po) and raloxifene hydrochloride (5 mg/kg po). Raloxifene was suspended in 0.25% water solution of carboxymethylcellulose, tacrolimus was suspended in distilled water. The drugs were administered by a stomach gavage (po) once daily for 4 weeks. The control rats received the vehicle in the same volume of 2 mL/kg po daily. The animals were weighed every second day. After 4 weeks of drug administration, the animals were sacrificed and the right and left tibial and femoral bones and L-4 vertebra were excised. In the isolated left bones, mass and macrometric parameters were determined (length, diameter of the diaphysis in the mid-length). Mass of the liver, testicles, kidneys and spleen was also determined. Bone mechanical properties were assessed using the set constructed at the Department of Pharmacology, Medical University of Silesia, in cooperation with Hottinger Baldwin Messtechnik GmbH. Mechanical properties of the whole femur and the femoral neck were examined, as previously described (9, 10). Mechanical properties of whole left femurs were studied using a bending test with three-point loading. The load was applied perpendicularly to the long axis of the femur in the mid-length of the bone supported on its epiphyses. The load increased at a rate of 100 N/min. The load was measured by the sensor with a strain gauge, the deformation was measured by an inductive sensor. The signals sent by the sensors were amplified and registered using the XY recorder. The load-deformation curves, obtained for each bone, representing the relationships between load applied to the bone and deformation in response to the load, were analyzed. The load-deformation curve can be divided into the elastic deformation region and the plastic deformation region. Within the elastic deformation region, the slope of load-deformation curve, representing the extrinsic stiffness of bone, was tested. Within the plastic deformation region, the ultimate load and the breaking load were determined. The ultimate load is the maximum load sustained by the bone. The breaking load is the load at which the bone actually breaks. Deformation caused by the applied loads was also measured. Mechanical properties of the femoral neck were studied using a compression test. The load was applied to the head of the femur along the long axis of the femur. The bone was prepared to the measurement by fixing the diaphysis, which was cut in 1.7 cm from the proximal end of the right femur, in a metacrylate plate. The load causing the fracture of the femoral neck was determined. In order to determine the content of mineral substances in bones, the L-4 vertebra, left tibia and femur were mineralized at the temperature of 640 O C for 48 h and weighed. Results are presented as the mean ± SEM. Statistical estimation was performed using ANOVA followed by post-hoc Duncanís test. When appriopriate (lack of homogeneity of variance), KruskalWallis ANOVA, followed by Mann-Whitney U test, was used to determine specific differences. RESULTS Administration of tacrolimus at a dose of 0.3 mg/kg po daily for 4 weeks did not affect body mass gain, the mass of liver and testicles Tacrolimus did not statistically significantly affect the length and diameter of the investigated long bones The results concerning the effects of administration of raloxifene at a dose of 5 mg/kg po on the Effect of low-dose tacrolimus coadministered with raloxifene... 20

Direct observation of the dead-cone effect in quantum chromodynamics

The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron

Direct observation of the dead-cone effect in quantum chromodynamics

At particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD) [1]. The vacuum is not transparent to the partons and induces gluon radiation and quark pair production in a process that can be described as a parton shower [2]. Studying the pattern of the parton shower is one of the key experimental tools in understanding the properties of QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass m and energy E, within a cone of angular size m/E around the emitter [3]. A direct observation of the dead-cone effect in QCD has not been possible until now, due to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible bound hadronic states. Here we show the first direct observation of the QCD dead-cone by using new iterative declustering techniques [4, 5] to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD, which is derived more generally from its origin as a gauge quantum field theory. Furthermore, the measurement of a dead-cone angle constitutes the first direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics.The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron.In particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD). These partons subsequently emit further partons in a process that can be described as a parton shower which culminates in the formation of detectable hadrons. Studying the pattern of the parton shower is one of the key experimental tools for testing QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass $m_{\rm{Q}}$ and energy $E$, within a cone of angular size $m_{\rm{Q}}$/$E$ around the emitter. Previously, a direct observation of the dead-cone effect in QCD had not been possible, owing to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible hadrons. We report the direct observation of the QCD dead cone by using new iterative declustering techniques to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD. Furthermore, the measurement of a dead-cone angle constitutes a direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics

Measurement of electrons from semileptonic heavy-flavour hadron decays at midrapidity in pp and Pb–Pb collisions at √sNN = 5.02 TeV

The differential invariant yield as a function of transverse momentum (pT) of electrons from semileptonic heavy-flavour hadron decays was measured at midrapidity in central (0–10%), semi-central (30–50%) and peripheral (60–80%) lead–lead (Pb–Pb) collisions at √sNN = 5.02 TeV in the pT intervals 0.5–26 GeV/c (0–10% and 30–50%) and 0.5–10 GeV/c (60–80%). The production cross section in proton–proton (pp) collisions at √s = 5.02 TeV was measured as well in 0.5 < pT < 10 GeV/c and it lies close to the upper band of perturbative QCD calculation uncertainties up to pT = 5 GeV/c and close to the mean value for larger pT. The modification of the electron yield with respect to what is expected for an incoherent superposition of nucleon–nucleon collisions is evaluated by measuring the nuclear modification factor RAA. The measurement of the RAA in different centrality classes allows in-medium energy loss of charm and beauty quarks to be investigated. The RAA shows a suppression with respect to unity at intermediate pT, which increases while moving towards more central collisions. Moreover, the measured RAA is sensitive to the modification of the parton distribution functions (PDF) in nuclei, like nuclear shadowing, which causes a suppression of the heavy-quark production at low pT in heavy-ion collisions at LHC

Higher harmonic non-linear flow modes of charged hadrons in Pb-Pb collisions at sNN\sqrt{s_{\rm{NN}}} = 5.02 TeV

International audienceAnisotropic flow coefficients, v$_{n}$, non-linear flow mode coefficients, χ$_{n,mk}$, and correlations among different symmetry planes, ρ$_{n,mk}$ are measured in Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV. Results obtained with multi-particle correlations are reported for the transverse momentum interval 0.2 < p$_{T}$< 5.0 GeV/c within the pseudorapidity interval 0.4 < |η| < 0.8 as a function of collision centrality. The v$_{n}$ coefficients and χ$_{n,mk}$ and ρ$_{n,mk}$ are presented up to the ninth and seventh harmonic order, respectively. Calculations suggest that the correlations measured in different symmetry planes and the non-linear flow mode coefficients are dependent on the shear and bulk viscosity to entropy ratios of the medium created in heavy-ion collisions. The comparison between these measurements and those at lower energies and calculations from hydrodynamic models places strong constraints on the initial conditions and transport properties of the system.[graphic not available: see fulltext