Amphiphilic and thermosensitive copolymers based on pullulan and Jeffamine: Synthesis, characterization and physicochemical properties

The synthesis of thermosensitive copolymers based on pullulan and polyether amine was performed in water using a water-soluble carbodiimide and N-hydroxysuccinimide as activators. Jeffamine^® M2005 was chosen as a polyether to impart thermosensitive character to the copolymer. Pullulan was modified into carboxymethylpullulan, to bring carboxylate groups to the polysaccharide so as to further the grafting reaction. The copolymers were characterized by FT-IR, ¹H NMR spectroscopy and molecular weights measurements (by SEC coupled with MALS/DRI/Viscometer lines). The thermosensitive behaviour of CMP-g-M2005 copolymers was studied by fluorescence spectroscopy of pyrene, by rheometry and microDSC measurements. The sol-gel transition temperature was found dependent on the solvent, the grafting degree of M2005 and the concentration of the copolymer. For example it was 35 °C in water, 28 °C in acid buffer (0.1 M, pH 5.4) and 26 °C in saline phosphate buffer (0.15 M, pH 7.4) for a grafting degree of 0.20 at a concentration of 5 wt%.     

Mollusc assemblages of the Pontian and Dacian deposits from the Topolog-Arge? area (southern Carpathian foredeep - Romania)

A better understanding of Mediterranean-Paratethys water-exchange during the Messinian Salinity Crisis has since long been hampered by the absence of a reliable time frame for the Paratethys. High-resolution magnetostratigraphic studies on the sedimentary sequences of the eastern and southern Carpathian foredeep recently resulted in an accurate chronology for the Mio-Pliocene deposits of the Dacic Basin of Romania. This allowed a straightforward correlation of the Pontian and Dacian stages to the geological time scale, which revived earlier discussions on Mediterranean-Paratethys connectivity. Here, we present Pontian and Dacian mollusc assemblages of the Getic Depression (Topolog-Arge? area, southern Carpathians) of Romania, which are incorporated in a magnetostratigraphic time frame. They indicate that a hiatus - comprising the Early Pontian - is present in the stratigraphic successions, which could be related to a base level drop of the Paratethys water column or to more local tectonic processes. The mollusc assemblages furthermore show a gradual transition at the Pontian/Dacian boundary, which is magnetostratigraphically dated at ∼4.9 Ma. This is significantly later (by more than 400 kyrs) than the Mio-Pliocene boundary in the Mediterranean sequences.     

Epidemiological surveillance of syphilis patients in Colentina Hospital (Bucharest, Romania)

Syphilis remains a global health problem with an estimated 12 million people infected each year. In Romania a decrease in the syphilis prevalence can be observed. From 2002 (12,702 cases) and 2003 (9,698 cases) until 2006 (5,657 syphilis cases) the reduction can be explained through the intensified efforts of the Ministry of Pubic Health to fight STI. The decrease is probably not related to an improvement of the general health status and not a consequence of some epidemiological prevention and control measures but probably was done by the reorientation of the patients to the general practitioners and to the private practice medical offices and to the lack of reporting of the cases. In Colentina Hospital a similar abrupt decrease of new cases was registered from 2004 (259 cases) to 2006 (110 cases). General problems related to syphilis cases recorded at Colentina Hospital included the patient presentation for consultation in the advanced stages of the disease, the socio-economic and educational factors, proxenetism and the sexual aggression of minors. There is a need in strengthening of the public health component in the control and surveillance of HIV/AIDS and STI. This may need changes in the legal framework to improve reporting and to target vulnerable groups in prevention activities. Laboratory capacity needs to be increased in order to be able to properly diagnose STI and improve the control and patient management. The reporting needs to be improved and simplified as for reporting protocol, reporting forms, case definitions to be taken into account in the renewed STI surveillance.     

Probabilistic finite element prediction of knee wear simulator mechanics

Computational models have recently been developed to replicate experimental conditions present in the Stanmore knee wear simulator. These finite element (FE) models, which provide a virtual platform to evaluate total knee replacement (TKR) mechanics, were validated through comparisons with experimental data for a specific implant. As with any experiment, a small amount of variability is inherently present in component alignment, loading, and environmental conditions, but this variability has not been previously incorporated in the computational models. The objectives of the current research were to assess the impact of experimental variability on predicted TKR mechanics by determining the potential envelope of joint kinematics and contact mechanics present during wear simulator loading, and to evaluate the sensitivity of the joint mechanics to the experimental parameters. In this study, 8 component alignment and 4 experimental parameters were represented as distributions and used with probabilistic methods to assess the response of the system, including interaction effects. The probabilistic FE model evaluated two levels of parameter variability (with standard deviations of component alignment parameters up to 0.5mm and 1 degrees ) and predicted a variability of up to 226% (3.44mm) in resulting anterior-posterior (AP) translation, up to 169% (4.30 degrees ) in internal-external (IE) rotation, but less than 10% (1.66MPa) in peak contact pressure. The critical alignment parameters were the tilt of the tibial insert and the IE rotational alignment of the femoral component. The observed variability in kinematics and, to a lesser extent, contact pressure, has the potential to impact wear observed experimentally.     

Diffusion of transcription factors can drastically enhance the noise in gene expression

We study by Green's Function Reaction Dynamics the effect of the diffusive motion of repressor molecules on the noise in mRNA and protein levels for a gene that is under the control of a repressor. We find that spatial fluctuations due to diffusion can drastically enhance the noise in gene expression. After dissociation from the operator, a repressor can rapidly rebind to the DNA. Our results show that the rebinding trajectories are so short that, on this timescale, the RNA polymerase (RNAP) cannot effectively compete with the repressor for binding to the promoter. As a result, a dissociated repressor molecule will on average rebind many times, before it eventually diffuses away. These rebindings thus lower the effective dissociation rate, and this increases the noise in gene expression. Another consequence of the timescale separation between repressor rebinding and RNAP association is that the effect of spatial fluctuations can be described by a well-stirred, zero-dimensional, model by renormalizing the reaction rates for repressor-DNA (un) binding. Our results thus support the use of well-stirred, zero-dimensional models for describing noise in gene expression. We also show that for a fixed repressor strength, the noise due to diffusion can be minimized by increasing the number of repressors or by decreasing the rate of the open complex formation. Lastly, our results emphasize that power spectra are a highly useful tool for studying the propagation of noise through the different stages of gene expression.     

The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat

AimThis study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl₄induced hepatopathy on rat.Material and methodsWe worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) – saline, group II – MK 5 mg/kg/day i.p. for 5 days, group III – MK 5 mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl₄ p.o., 0.3 ml/Kg/day and group IV – CCl₄, p.o., 0.3 ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate.ResultsCompared to group IV, group III exhibited statistically significant lower levels of ALT (318 ± 15.75 versus 203.14 ± 10.28 UI, p < 0.0001), TB (3.16 ± 0.30 versus 1.99 ± 0.08 mg/dl, p < 0.0001), MDA in blood and in liver homogenate (4.98 ± 1.71 versus 2.15 ± 1.18 nmol/ml, p = 0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions.ConclusionMK exhibits a partial hepatoprotective effect on rats treated with CCl₄.     

Calculation of Fluctuating Asymmetry of the biggest Caspian whipsnake population in Hungary compared to a common snake species

The Fluctuating Asymmetry (FA) is a special type of asymmetry in the populations of bilaterally symmetrical creatures. The FA gives us numerical data on the developmental instability of the populations and refers to potential genetical and environmental stressors affecting the populations. Here we give the first data on the FA of the protected Caspian whipsnake (Hierophis caspius) from Hungary. The FA indices of the biggest population from Villány Mts were compared to the FA indices of two differently stressed Dice snake (Natrix tessellata) populations [stressed (Mád) and seminatural (Lake Balaton)]. Based on the values of the multiple and the simple indices derived from sublabial scales, we can say that the status quo of the highly protected Caspian whipsnake population does not represent significant deviation from the near-natural dice snake population from the Lake Balaton.     

Seasonal variation in stable C and N isotope ratios of the Rhone River inputs to the Mediterranean Sea (2004–2005)

The temporal variation in the stable carbon and nitrogen isotope ratios of particulate organic matter (POM) in the Rhone River was investigated on a monthly basis during a 2-year period (2004–2005). In spite of high month-to-month variation, interannually consistent seasonal trends appeared, with significantly lower δ¹³C (<?28.2‰) in spring than in the other seasons. In contrast, δ¹⁵N did not exhibit significant temporal variation. In spring and summer, high chlorophyll a and b concentrations were associated with low C/N values (<8) and a high percentage of organic carbon (%C) and organic nitrogen (%N), testifying to high development of autochthonous riverine phytoplankton (mainly diatoms and chlorophytes). In fall and winter, higher δ¹³C (>?27.2‰) and C/N (>8) values, and lower %C, %N, and chlorophylls concentrations indicated the predominance of allochthonous terrestrial detritus material in the river POM. The lower δ¹³C values recorded in spring–summer, when the phytoplankton biomass was high, were related to the lower carbon isotopic signatures of freshwater diatoms and chlorophytes compared to those of terrestrial plants. Overall, Rhone River POM was mainly composed of terrestrially derived material (90%), with autochthonous phytoplankton representing only 10% as a mean, in spite of a higher mean contribution of phytoplankton (27%) to river POM in summer.     

Medical significance and new therapeutical strategies for biofilm associated infections

Recent public announcements stated that 60% to 85% of all microbial infections involve biofilms developed on natural tissues (skin, mucosa, endothelial epithelia, teeth, bones) or artificial devices (central venous, peritoneal and urinary catheters, dental materials, cardiac valves, intrauterine contraceptive devices, contact lenses, different types of implants). Prosthetic medical devices are risk factors of chronic infections in developed countries and these infections are characterized by slow onset, middle intensity symptoms, chronic evolution and resistance to antibiotic treatment. In case of biofilm development, a series of genes (40-60% of the prokaryotic genome) are modulated (activated/inhibited) by complex cell to cell signalling mechanisms and the biofilm cells become phenotypically distinct from their counterpart--free cells, being more resistant to stress conditions (including all types of antimicrobial substances); this resistance is phenotypical, behavioural and, more recently, called TOLERANCE. Four major mechanisms can account for biofilm antibiotic tolerance: (1) the failure of antibiotic penetration into the depth of a mature biofilm due to the biofilm matrix; (2) the accumulation of high levels of antibiotic degrading enzymes; (3) in the depth of biofilm, cells are experiencing nutrient limitation entering in a slow-growing or starved state; slow-growing or non-growing cells being not highly susceptible to antimicrobial agents, this phenomenon could be amplified by the presence of phenotypic variants or "persisters" and (4) biofilm's bacteria can turn on stress-response genes and switch to more tolerant phenotypes on exposure to environmental stresses; (5) genetic changes, probably selected by different stress conditions, such as mutations and gene transfer could occur inside the biofilm. In these conditions, biofilm associated infections require a different approach, both clinically and paraclinically.