Ceramide profiles in the brain of rats with diabetes induced by streptozotocin

Diabetes is associated with disturbances of brain activity and cognitive impairment. We hypothesize that ceramides may constitute an important contribution to diabetes-linked neuro-dysfunction. In our study we used rats injected with streptozotocin (STZ) as a model of severe hyperglycemia. Using the gas-liquid chromatography technique we found a significant increase of ceramide content in brains and a decrease in plasma of diabetic rats. The inhibitor of serine palmitoyltransferase, myriocin, reduced ceramide generation in hyperglycemic brains, although injected alone it exerted a paradoxical effect of ceramide upregulation. Myriocin had no impact on ceramide concentration in the plasma of either control or diabetic rats. The level of ceramide saturated fatty acids was elevated whereas the level of ceramide poly-unsaturated fatty acids was downregulated in brains of all experimental groups. The concentration of ceramide mono-unsaturated fatty acids remained unchanged. The pattern of individual ceramide species was altered depending on treatment. We noted an STZ-evoked increase of brain ceramide C16:0, C18:0 and C20:0 and a strong decline in ceramide C18:2 fatty acid levels. Some changes of brain ceramide pattern were modified by myriocin. We found a decreased amount of total ceramide-ω-6 fatty acids in STZ-treated rat brains and no changes in ceramide-ω-3 concentration. We conclude that ceramides may be important mediators of diabetes-accompanied brain dysfunction.     

Short term synaptic depression model--analytical solution and analysis

In this article we present analytical solutions of the single and pair pulse time evolution of a plastic neocortical synapse described by the TM-model. We show that this model is equivalent to the receptor-desensitization model with three kinetic states. For the TM-model we derive the analytical form of a measure of paired pulse depression. We analyze the sensitivity of the synaptic depression phenomenon on model parameters and derive the relative importance of each of the parameters. The closed form of the measure of synaptic depression allows fitting the model to experimental data. The fitted parameters are used to make predictions about the asymptotic properties of the postsynaptic currents. We show that for synapses with the ratio of inactivation and recovery rates of the same order, the synaptic depression does not preclude the rate-coding of information: e.g. in the pyramid-pyramid connections of adult rat neocortex, rate-coding is possible for higher frequencies.     

Susceptibility to antimicrobial agents and genotypic relatedness of enterococcal strains isolated from patients and hospital environment

The aim of this study was to evaluate antibiotic susceptibility of Enterococcus sp. strains isolated from two hospitals in ?ód?, during 2005-2006. The second goal was to determine possible transmission of these strains within hospital wards by using melting profile PCR. Enterococcal strains were identified to species according standard microbiological methods. There was isolated 159 strains of E. faecalis, 51 strains of E. faecium and two E. avium, 1 E. durans. Susceptibility to antimicrobial agents was tested by disc diffusion method. None of these strains was resistant to vancomycin, teicoplanin or linezolid. There was high percentage of strains resistant to aminoglicosides, 22% of E. faecalis strains, and 54.9% of E. faecium strains, respectively. Additionally it was shown that 11.7% of E. faecium is resistant to chinuprisin-dalfopristin. The strains with similar pattern of resistance to antibiotics and fenotypic characteristics were genotyped by mpPCR. This technique was useful to confirm relatedness of bacterial strains suspected of being spread within hospital wards.     

Decrease in sex difference in premature mortality during system transformation in Poland

In recent years, sex differences in mortality have followed diverse patterns of change in developed countries. As there is no analogous evidence from Poland, the aim of this study was to describe the pattern of change in excess male mortality among Polish inhabitants aged 35-64 during 1995-2002, when the major socioeconomic transformation occurred, and compare it with sex differences in mortality observed in the late 1980s. During the study period, excess male mortality decreased significantly, independently of age and educational level. The reduction in mortality was observed in both sexes, but its magnitude was greater in men. These changes resulted mainly from a reduction in mortality rates due to cardiovascular disease and lung cancer in males and a concomitant increase in mortality rates due to lung cancer and suicides in females. Although, in general, excess male mortality decreased, social gradients related to this phenomenon increased. Subjects (in particularly men) who had graduated from university benefited the most, their magnitude of reduction in mortality rates being the greatest. Changes in social environment during the transformation period in Poland are suggested as major determinants of these changes, but further studies are needed.     

Growth hormone therapy in boy with panhypopituitarism may induce pilomatricoma recurrence: case report

Pilomatricoma is usually a solitary subcutaneous nodule. Recurrence of the nodule after surgical excision is very rare. Pilomatricoma occurrence in patients with growth hormone (GH) deficiency has not been reported, yet. We report a 14-year-old boy with pilomatricoma and panhypopituitarism. After GH therapy had been started, we observed two relapses of previously completely excised pilomatricoma in the same location and a new pilomatricoma formation on the chin.     

Estimation of binding parameters for the protein–protein interaction using a site-directed spin labeling and EPR spectroscopy

Sensitivity of the electron paramagnetic resonance (CW EPR) to molecular tumbling provides potential means for studying processes of molecular association. It uses spin-labeled macromolecules, whose CW EPR spectra may change upon binding to other macromolecules. When a spin-labeled molecule is mixed with its liganding partner, the EPR spectrum constitutes a linear combination of spectra of the bound and unbound ligand (as seen in our example of spin-labeled cytochrome c ₂ interacting with cytochrome bc ₁ complex). In principle, the fraction of each state can be extracted by the numerical decomposition of the spectrum; however, the accuracy of such decomposition may often be compromised by the lack of the spectrum of the fully bound ligand, imposed by the equilibrium nature of molecular association. To understand how this may affect the final estimation of the binding parameters, such as stoichiometry and affinity of the binding, a series of virtual titration experiments was conducted. Our non-linear regression analysis considered a case in which only a single class of binding sites exists, and a case in which classes of both specific and non-specific binding sites co-exist. The results indicate that in both models, the error due to the unknown admixture of the unbound ligand component in the EPR spectrum causes an overestimation of the bound fraction leading to the bias in the dissociation constant. At the same time, the stoichiometry of the binding remains relatively unaffected, which overall makes the decomposition of the EPR spectrum an attractive method for studying protein–protein interactions in equilibrium. Our theoretical treatment appears to be valid for any spectroscopic techniques dealing with overlapping spectra of free and bound component.     

Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice

This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.     

Changes of serum albumin affinity for aspirin induced by fatty acid

Saturated fatty acids such as myristic acid play an important role in the pathogenesis of cardiovascular disorders.

Using the quenching fluorescence method we examined the influence of myristate on the changes of transporting protein affinity towards aspirin—the most popular anticoagulant.

Our results showed that the presence of the myristic acid alters the stability of the anticoagulant–albumin complex. The ranges of [myristate]/[albumin] molar ratio at which the stability of drug–protein complex increases or decreases were determined. The differences in interaction between ligands and human or bovine serum albumins were identified. The competition in binding of ligands with these albumins was also described.     

Study of X-ray and neutron emission in experiments with Al wires in an MA plasma focus

Results are presented from experimental studies of the correlation between X-ray and neutron emissions generated in the implosion of a deuteron plasma shell onto an Al wire. The experiments were carried out on the PF-1000 facility at currents of 1.5–1.8 MA. An Al wire 80 μm in diameter and 7–9 cm in length was placed at the end of the inner electrode. During the implosion of the plasma shell, Al K-shell X-rays were first emitted at the dip of the current derivative. After the X-ray pulse, a relatively stable corona with a diameter of 2–3 mm and lifetime of a few hundred nanoseconds formed around the wire. The presence of the wire did not considerably reduce the total neutron yield (at most 10¹¹ neutrons per shot) in comparison to discharges without a wire. As a rule, the intensity of neutron emission was maximal a few tens of nanoseconds after the peak of X-ray emission. A detailed comparison of two shots with low and high neutron yields have shown that the neutron yield depends on the configuration and dynamics of the discharge. The possible influence of the self-generated axial component of the magnetic field on the development of the plasma focus and the acceleration of fast deuterons is discussed.