Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion

Molecular and chemical neuropathology - Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were...     

Polymerization in inverse microemulsions, 4 locus of initiation by ammonium peroxodisulfate and 2,2′-azoisobutyronitrile

The locus of the initiation using the water-soluble radical initiator ammonium peroxodisulfate (APS) and/or the partially water-soluble radical initiator 2,2′-azoisobutyronitrile (AIBN) in the inverse microemulsion system toluene/water (mass ratio 10:1) was studied. The homopolymerization and/or copolymerization of the water-soluble monomer acrylamide (AAM) with the oilsoluble methyl methacrylate (MMA) was investigated. It was found that the locus of initiation by APS in the given system is the water micropool, and the locus of initiation by AIBN is the interlayer between the water micropool and the toluene macrophase.     

Polymerization of vinyl monomers photoinitiated by benzoylated polystyrene

The rate of the polymerization of vinyl monomers photoinitiated (at λ = 365 nm) by benzoylated polystyrene in N,N-dimethylformamide (DMF) decreases in the sequence vinyl acetate>acrylonitrile>methyl methacrylate ? styrene ≈ 0 and is related to the rate constant of propagation of the mentioned monomers. In addition to DMF, aromatic hydrocarbons (benzene, toluene, p-xylene), cyclohexane and tetrahydrofuran were employed as hydrogen donors. The maximum polymerization rate was achieved in the system containing p-xylene; the system with benzene turned out inefficient for the initiation of acrylonitrile polymerization. Turbidimetric titration of a soluble fraction of the acrylonitrile polymerization in DMF in presence of benzoylated polystyrene showed that the soluble fraction does not contain graft copolymers of benzoylated polystyrene with acrylonitrile. It is assumed, however, that the polyacrylonitrile in the insoluble fraction is bound to benzoylated polystyrene in the form of graft copolymers.     

The MD-MPH program at the University of North Carolina at Chapel Hill.

In 1997, the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill (UNC) developed a formal MD-MPH program, called the Health Care and Prevention (HC&P) Program, located in the Public Health Leadership Program in the UNC School of Public Health. Since then, and especially since 2003, the number of UNC medical students taking a year out of their medical studies to pursue an MPH has increased dramatically. At present, more than 20% of UNC medical students enter an MPH program at some point between entering medical school and leaving for residency.The HC&P Program is designed to introduce clinicians to the population sciences and to create physicians who can think in both individual and population terms. The curriculum is a rigorous, 12-month program that includes a practicum experience and a master's paper. Several of the traditional MPH introductory courses have been redesigned to be more relevant to physicians. The program allows a maximum number of electives and places a value on flexibility so that students, together with faculty, can design the educational experience that best meets their needs. Many members of the faculty of the program themselves have both MD and MPH degrees, and some have dual appointments in the schools of medicine and public health.The authors have begun a longitudinal cohort study of program graduates and other medical graduates to understand the effect of the program on students' perceptions of their competency and their ability to exert leadership in various areas of population health.     

Radical reactions initiated by chelate complexes of transition metals, 12. Decomposition of cumene hydroperoxide by the system copper acetate-aminoalcohol

This paper presents an investigation of the kinetics of the decomposition of cumene hydroperoxide (1-methyl-1-phenylethyl hydroperoxide) (CHP) in benzene/methanol (95:5, by vol.) in the presence of copper(II) acetate (A) and different aminoalcohols (L), such as 2-aminoethanol, 2-(2-hydroxyethylamino)ethanol, 2-[bis(2-hydroxyethyl)amino]ethanol, 1-amino-2-propanol, and 2-(diethylamino)ethanol. It has been found that the decomposition of CHP takes place via a complex formed from the components of the reaction system. The individual components of the catalytic system (i. e. A or L), when applied separately, do not contribute to an acceleration of the decomposition reaction. Under the given conditions the initial rate of the CHP decomposition v_o is expressed formally by the equation where [A₂]₀, [L]₀, and [CHP]₀ are the initial concentrations of the above mentioned compounds; k is the monomolecular rate constant for the decomposition of the complex between metal compound and CHP, and K_L, K_c and K_A are the equilibrium constants for the formation of the adduct from aminoalcohol and copper(II) acetate, the formation of the complex consisting of this adduct and CHP and for the dimerisation of copper(II) acetate, resp.     

On the interaction of styrene-maleic anhydride copolymer with styrene

The interaction between alternating styrene/maleic anhydride copolymer as polymeric acceptor and styrene as low molecular weight donor in acetone and/or tetrahydrofuran was investigated by UV spectroscopy and polymerization technique. The equilibrium constant for the complex formation between styrene and the maleic anhydride structural unit of the styrene/maleic anhydride copolymer at 20°C was found to be 0,02 ± 0,001 dm³·mol^?1 in acetone and 0,06 ± 0,003 dm³·mol^?1 in tetrahydrofuran. The results of the thermally initiated polymerization of styrene in acetone in the presence of the alternating styrene/maleic anhydride copolymer indicate that the copolymer or the products of the interaction between the monomeric units of maleic anhydride in the copolymer and styrene do not initiate a radical polymerization of styrene.     

Interspecies differences in the kinetic properties of deoxycytidine kinase elucidate the poor utility of a phase I pharmacologically directed dose-escalation concept for 2-chloro-2′-deoxyadenosine

2-Chloro-2-deoxyadenosine (CdA, Cladribine), is a purine antimetabolite currently under investigation in phase II clinical trials for the treatment of lymphoid malignancies. Significant differences in CdA toxicity between mice and humans were observed during phase I clinical evaluation. For the elucidation of interspecies differences in drug toxicity the pharmacokinetics of CdA after subcutaneous injection and the kinetic properties of the CdA-phosphorylating enzyme, deoxycytidine kinase (dCK), were compared in mice and humans. The ratio of the dose lethal to 10% of mice (LD₁₀) to the maximum tolerated dose (MTD) in humans was 50 and the ratio of the area under the curve obtained at approximately one-half the LD₁₀ (AUC_{approx. one-half the LD 10})/AUC_MTD was 49. A significant interspecies difference was observed in the kinetic properties of dCK, the main CdA-activating enzyme. With CdA as a substrate, the Michaelis constant (K _m) of dCK in crude extracts of mouse thymus was 10 times higher than that in human thymus. An approximately 9-fold interspecies difference in maximum velocity (V_max)/K _m indicated a higher efficiency of dCK for CdA in humans than in mice. The peak plasma concentration was 210 times higher and exceeded theK _m in mice. Initial and terminal half-lives were approximately 7 times shorter in mice and trough levels were similar in mice and humans. Thus, the differences in AUCs at equitoxic doses are largely explained by differences in the target enzyme properties and the pharmacokinetic pattern. The observed lower tolerance for CdA in humans as compared with mice confirms the view that antimetabolites may not be good candidates for pharmacokinetically guided dose-escalation schemes unless detailed information on interspecies variability in drug bioactivation is available.     

Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy‐number alterations (CNAs) in 90 MGUS and 33 MM patients using high‐density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10^?5) and showed median number of CNAs is lower in MGUS (3, range 0–22) than in MM (13, range 4–38, P = 1.82 × 10^?10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.     

The prevalence of HPV infections in HPV‐vaccinated women from the general population

Currently, three prophylactic HPV vaccines are commercially available to prevent HPV 16/18 infection and associated lesions. The aim of the study was to assess markers of HPV infection in women/girls before vaccination and to ascertain the prevalence and spectrum of post‐vaccination HPV types. Three hundred and thirty subjects of which 75 were virgins were enrolled. Before the first dose of the HPV vaccine and 1, 3 and 5 years after the completion of HPV vaccination, the samples for cytology, HPV detection and anti‐HPV antibody response were taken. At enrolment, HPV DNA was detected in 38% of sexually active girls/women. At the first, second and third follow‐up, HPV DNA was found in 40, 45, and 39% of them. The seroprevalence rates to HPV 6, 11, 16 and 18 in these subjects were 31, 21, 18 and 10%. On the follow‐up significantly higher levels of antibodies to HPV 16/18 were found after application of divalent vaccine. Results of the study demonstrate high prevalence of HPV infection in young women. In a substantial number of women, HPV‐specific antibodies as well as high‐risk HPV types were detected. HPV‐specific antibodies were also frequently found in non‐sexually active girls. The acquisition of HPV after the onset of sexual life was very fast.