Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats

A plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, succinate dehydrogenase (SDH). Inhibition of SDH disturbs electron transport and leads to cellular energy deficits and neuronal injury. We have shown that pretreatment with l-carnitine, while not significantly attenuating SDH inhibition, prevented hypothermia and oxidative stress-associated increased activity of free radical-scavenging enzymes. Here, a neurohistological method was applied to examine the effect of carnitine pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats were randomly divided into two groups (n = 10/group). Rats in the first group were injected twice with 3-NPA at 30 mg/kg s.c., 2 days apart, and the second group of animals received l-carnitine pretreatment at 100 mg/kg 30-40 min before 3-NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. In the three animals that survived 3-NPA dosing, one exhibited no pathology, one exhibited moderate unilateral damage to the striatum, and the third exhibited extensive bilateral neuronal degeneration in multiple forebrain regions. In the seven surviving animals that received l-carnitine prior to 3-NPA insult, six exhibited no lesions, while one exhibited a modest unilateral lesion in the striatum. It appears that l-carnitine is protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration.     

Anionic block polymerization of β-lactones initiated by potassium solutions, 1. Synthesis of poly(4-methyl-2-oxetanone-block-2-oxetanone)

The block polymerization of 4-methyl-2-oxetanone (β-butyrolactone) with 2-oxetanone (β-propiolactone) proceeds fast with a yield of more than 90%, in the presence of potassium solutions in THF containing 18-crown-6. Poly(4-methyl-2-oxetanone-block-2-oxetanone) polymers having the expected molecular weight and composition are formed by this way. Their glass transition and melting temperatures as well as their melting enthalpies, determined by DSC, show a strict correlation with block polymer composition.     

Hepatic lysosomal enzymes activity and liver morphology after short-time omeprazole administration

The aim of the study was to establish the influence of short-time omeprazole administration on liver function and morphology. Omeprazole was administered intraperitoneally, twice daily, for 3 days to male Wistar rats in two doses: 0.571 mg/kg and 5.71 mg/kg. Control animals were treated with physiological saline. Half of the animals were sacrificed 12 hours after the last injection. The remaining rats were raised for another 6 weeks, without any xenobiotics, and sacrificed on the 47th day of the experiment. The activity of free and bound fractions of hepatic acid phosphatase, beta-galactosidase, beta-N-acetyl-glucosaminidase, cathepsin B, D and L, lipase, and sulphatase were determined spectrophotometrically in homogenates of the liver. The liver sections were examined by light microscopy with hematoxylin-eosin, azan, and periodic acid-Schiff stains. Marginally significant (p < 0.1) differences in activity of free sulphatase fraction, and free and bound fractions of beta-galactosidase were found in animals exposed to the higher dose of omeprazole and sacrificed 12 hours after the last injection. Enzymatic profiles were normalised during the next 6 weeks. Histological evaluation revealed small degenerative and adaptive changes in all examined groups. It could be concluded that observed differences of hepatic lysosomal enzyme activities were the result of accompanied chemical-induced peritonitis as previously reported, and not a direct drug-toxic effect.     

Red blood cell glutathione peroxidase activity in multiple sclerosis

Summary Glutathione peroxidase (GSH-Px) activity of red blood cells of 23 multiple sclerosis (MS) patients (10 men and 13 women, aged 22–64 years) was examined and compared to the enzyme activity of 26 healthy persons (15 men and 11 women, aged 19–50 years). It was found that the mean GSH-Px activity was significantly higher (P<0.001) in red blood cells of MS patients (39.1±8.1 IU/g Hb) as compared to the group of healthy persons (25.9±5.2 IU/g Hb). There was no difference according to sexes in both the MS patients and the control group. The results are discussed based on the hypothesis that organic peroxides play a role in the etiology of multiple sclerosis.     

Coordination polymerization of lactides, 1. Structure determination of obtained polymers

Racemic lactide was polymerized with various initiators containing Zn and Al, and the structures of the obtained polymers were determined by means of ¹³C NMR spectroscopy. The extent of transesterification reactions was calculated on the basis of the analysis of the methine carbon signal in the polymer ¹³C NMR spectra. Three groups of initiators can be distinguished in view of their influence on transesterification: ZnCl₂ exhibits the strongest transesterification activity, ZnEt₂ and ZnEt₂/Al(OiPr)₃ are among those of medium activity, and Al(acac)₃ does not show transesterification activity at all.     

Telechelic poly(ε-caprolactone) terminated at both ends with OH groups and its derivatization

The synthesis of highly uniform (1,08 ≤ M _w/M _n ≤ 1,13) telechelic poly(ε-caprolactone) terminated at both ends with OH groups and its derivatization leading to poly(ε-caprolactone) with pyrene end-groups are described. The synthesis, carried out in THF at room temperature, involves initiation with (CH₃CH₂)₂AlO(CH₂CH₂O)₃Al(CH₂CH₃)₂, leading to poly(ε-caprolactone) macromolecules growing at both ends. The active centers were deactivated with acetic acid, giving macromolecules with OH end-groups. Reaction of α,ω-dihydroxypoly(ε-caprolactone), HO-poly(εCL)-OH, with 4-(1-pyrenyl)butyryl chloride yields α,ω-di-1-pyrenylpoly(ε-caprolactone), Py-poly(εCL)-Py. Polymers are characterized by GPC, ¹H NMR, and UV spectroscopies. The UV spectra of polymers with pyrene end-groups are compared with the UV spectra of the model compound.     

Anionic block polymerization initiated by potassium solutions, 2. Synthesis of poly(2-oxetanone)-block-polystyrene-block-poly(2-oxetanone)

The block polymerization of styrene with 2-oxetanone (β-propiolactone) proceeds fast with a yield of more than 90%, in the presence of potassium solutions in THF containing 18-crown-6. Poly(2-oxetanone)-block-polystyrene-block-poly(2-oxetanone) ABA triblock polymers having the expected molecular mass and composition are formed. Their glass transition and melting temperatures as well as their melting enthalpies determined by DSC show a strict correlation with block polymer composition. The mechanism of this block polymerization involving acyloxygen and alkyl-oxygen bond scission in 2-oxetanone is in good agreement with previous results of the homopolymerization of β-lactones by alkali metal solutions abounding in potassium anions.     

Vinyl monomer complexes in copolymerization processes. Studies on the complexes of acrylonitrile and methyl methacrylate with lewis acids

Complexes of acrylonitrile and of methyl methacrylate with various Lewis acids, 1 and 2 , were studied by means of IR, NMR, and UV spectroscopy. The influence of the Lewis acid strength on the induction effect and on the delocalization of π-electrons in the complexed monomer molecule was established. As the relative acidity of the complexing agent is increased, the inductive effect of the nitrile or of the carbonyl group in the complex molecule rises, whereby the electron density on the carbon atom in β-position in the vinyl group diminishes. Complexation of the monomer also results in increased delocalization of π-electrons in the molecule. In the complexes with moderately strong Lewis acids like CH₃AlCl₂ and C₂H₅AlCl₂, delocalization of π-electrons seems to reach its maximum. The methyl methacrylate-C₂H₅AlCl₂ complex was found to give a charge-transfer complex with 1,5-cyclooctadiene. On the basis of the present spectroscopic studies and of earlier studies on copolymerization of acryl monomers with butadiene, the delocalization of π-electrons in the complexed monomer molecule is believed to be one of the major factors controlling the rate of copolymerization.     

Copolymerization of ethylene oxide and sulfur dioxide initiated by lewis bases

Sulfur dioxide undergoes copolymerization with ethylene oxide in the presence of Lewis bases capable of forming onium ions (such as amines, phosphines, diethyl sulfide, dimethyl sulfoxide, N,N-dimethylformamide) yielding poly(ethylene sulfite) bearing also a small amount of ethylene oxide monomeric units homosequencies. After 4–6 h of reaction at 50°C in bulk, the monomer conversion reaches 70–90%. The copolymer obtained is a mixture of linear and cyclic products which tend to degrade to yield ethylene sulfite. At 50°C this decomposition is very slow when unreacted SO₂ is completely removed. However, it proceeds very rapidly, within a few hours, in the presence of compounds with strong electrophilic properties like BF₃, H₃PO₄, or chlorotrimethylsilane. Studies of model reactions indicate that in the systems studied the macrocyclization results mainly from the attack of sulfite or alcoholate active species at the carbon atoms in polysulfites. Chain transfer reactions with the solvent occur also in reactions carried out in ethanol.     

Human heat shock protein 60 (409-424) fragment is recognized by serum antibodies of patients with acute coronary syndromes.

Acute coronary syndromes (ACS), including unstable angina (UA) and acute myocardial infarction (MI), are clinical manifestations of a progressive atherosclerotic process. Antibodies (Ab) to heat shock proteins (hsp) have been reported to be associated with atherosclerosis. Blood samples from 35 patients with ACS and 20 healthy volunteers were tested for Ab to human hsp60 by an enzyme-linked immunosorbent assay (ELISA). Levels of specific serum Ab against hsp60 were significantly elevated in patients with ACS when compared to clinically healthy subjects. To determine the antigenic determinants recognized by these Ab, antibody binding to seven peptides, selected from the hydrophilic and acrophilic regions of the human hsp60 molecule, was assessed. Despite the individual variation in the immune response among patients, one immunodominant region was revealed corresponding to the hsp60 (409-424) peptide. The identification of this epitope may be important for understanding the function of this protein in the atherosclerotic process.