Polymerization of lactams, 58. Nonactivated polymerization of 2-pyrrolidone in the presence of higher lactams

Addition of a higher lactam (ε-caprolactam or 8-octanelactam) to the nonactivated polymerization of 2-pyrrolidone, initiated with potassium tert-butoxide or the isolated potassium salt of 2-pyrrolidone, does not lead to the formation of a copolyamide. Only a marked decrease of polymerization rate is observed and the maximum rate of 2-pyrrolidone homopolymerization shifts to a lower temperature. The possible causes of this interesting phenomenon are discussed.     

Internal mobility of PMMA in concentrated CDCl3 solutions, 2. 13C NMR spectra

The ¹³C NMR relaxation parameters (T₁, line widths and NOE factors) were measured and analyzed for two samples of atactic poly(methyl methacrylate) (PMMA) of molecular weight M_w 4,20·10⁴ and 1,76.10⁶ in CDCl₃ solutions in the concentration range 11 to 54% (by weight) of polymer, at 297 and 323 K. By this analysis it was found that the backbone segmental motion of PMMA is spatially isotropic in the whole measured concentration range; the motion of the α-CH₃ group may be approximated by the double reorientation model; the motion of the ester CH₃ group can be approximated by the isotropic model only at concentrations lower than 12%; in more concentrated solutions, a satisfactory approximation is obtained neither by the isotropic, nor by the double reorientation models. The reasons of this behaviour are discussed.     

Search for XYY syndrome in psychiatrically disturbed children and adolescent juvenile delinquents

Two groups of young males were analyzed: 18 patients from the Division of Child Psychiatry, University of Minnesota, and 28 juvenile delinquents from Lino Lakes Juvenile Detention Center. All patients were screened regarding stature and behavior characteristics. None of the 46 cases analyzed showed any abnormality, either of autosomal or of sex chromosomes.Presented at the Fifth World Congress of Psychiatry, November 25–December 4, 1971, Mexico.     

On the copolymerization of acrylonitrile with styrene in the presence of Lewis acid, 2. Regulation of molecular weight

The results of the study of the acrylonitrile (AN)-sytrene (St) copolymerization in the presence of zinc chloride and various hydrogen donors (cyclohexane, octane, isooctane, and decahydronaphthalene) are reported. It was found that the rate of copolymerization (R_p) increases with concentration of the hydrogen donor at constant concentrations of comonomers in acetone in the presence as well as in the absence of a free-radical source (AIBN). The dependence of the reciprocal value of limiting viscosity number (1/[η]) of the equimolar copolymers on R_p in the system St? AN? ZnCl₂? AIBN is not linear. The position of the minimum on this curve at a given ratio of comonomers depends on the concentration of both zinc chloride and AIBN. The reduction of [η] of the equimolar copolymer attained by the effect of hydrocarbon is relatively small provided the reaction system is homogeneous. On the basis of the results obtained, it may be stated that a change in molecular weight of the copolymer is to be achieved more easily by a change in the rate of copolymerization (effected by AIBN) than by the effect of hydrogen donor (chain transfer).     

Increased systemic efficacy of aphidicolin encapsulated in liposomes

Aphidicolin, a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, is under investigation as anti-cancer drug. Because of its poor solubility in water, it cannot be administered directly in vivo. Systemic application of aphidicolin glycinate or aphidicolin gamma-cyclodextrin complexes resulted in tumour growth inhibition but not in cures. To improve the pharmacokinetics, a liposomal preparation of aphidicolin was developed and tested in neuroblastoma-bearing (UKF-NB-3) mice. The loading capacity of these liposomes was limited. Therefore, 4.5 mg aphidicolin/kg body weight was the maximum aphidicolin dose that could be applied as liposomal preparation in this approach. Comparison of effects on tumour growth exhibited by aphidicolin liposomes (4.5 mg aphidicolin/kg) given for 15 consecutive days to those of gamma-cyclodextrin inclusion complexes (15 mg aphidicolin/kg) revealed comparable tumour growth inhibition, although aphidicolin concentrations were approximately 3-fold lower. This shows that liposomal encapsulation is a promising strategy for the improvement of systemic anti-cancer activity of aphidicolin.     

Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression

Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20). UKF-NB-3rVCR10 and UKF-NB-3rDOX20 overexpressed functional P-gp and developed an increased malignant phenotype: presented constitutive phosphorylation of AKT, resistance to gamma-irradiation, and had increased survival in serum-free medium. Inhibition of P-gp restored chemosensitivity but did not affect increased survival in serum-free medium and sensitivity to gamma-irradiation. Inhibition of AKT had no influence on chemoresistance but restored sensitivity to serum starvation. Both resistant cell lines acquired additional chromosomal changes. UKF-NB-3rVCR10 cells acquired a missense P53 mutation in exon 5, an increased MYCN amplification, an enhanced adhesion to endothelium, a decreased NCAM expression, a distinctly higher clonogenicity, and an increased in vivo tumorigenicity. We conclude that acquisition of increased malignant behavior in neuroblastoma occurs concomitantly with multidrug-resistance and is P-gp-independent.     

Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria

Preclinical studies have shown that curdlan sulphate (CRDS), a sulphated 1-->3-beta-D glucan, inhibits Plasmodium falciparum in vitro and down-modulates the immune response. A direct, non-specific effect on cytoadherence and rosetting may be predicted, as has been described with other sulphated polysaccharides, e.g. heparin. The anticoagulant effect of CRDS is 10-fold lower than heparin. Curdlan sulphate has, therefore, emerged as a candidate for adjunct medication in the treatment of severe/cerebral malaria. Two clinical studies were conducted using CRDS as adjunct medication to conventional therapy (artesunate) in patients with severe and severe/cerebral malaria. Both studies were double-blind and placebo-controlled to evaluate the efficacy and safety of the combination. Curdlan sulphate appeared to reduce the severity of the disease process, e.g. fever clearance time was shortened. Due to the small number of patients, there was no difference in mortality. The two treatment arms in both studies showed similar results for all laboratory parameters. The only adverse event recorded during CRDS treatment was an increase in activated partial thromboplastin time. This can be monitored easily. It seems that the patients who may benefit most are severe/cerebral cases with no organ damage on admission.     

Management of ischemic deformity after the treatment of developmental dysplasia of the hip

Long-term results of 69 hip operations for deformities due to avascular necrosis following the conservative treatment of the hip dysplasia were evaluated. The authors' technique of intertrochanteric valgus osteotomy allows for simultaneously handling of varus deformity and shortening of the femoral neck, fusion of the greater trochanter, and correction of increased femoral anteversion, if necessary. This type of surgery was used in children with Buchholz-Ogden type III deformity starting from 3 years of age until adolescence. Patients were followed for an average of 19.3 years. Eighty-seven percent had no marked limitation in range of motion and 57% were free of complaints. Trendelenburg gait was present in only six patients. Radiographs of all patients showed improvement of coxometric values. Acetabular dysplasia was handled in 29 patients with a subsequent shelf arthroplasty. Total hip arthroplasty for hip degeneration was not indicated for any of the patients to date.     

Comparison of the effect of amphotericin B desoxycholate and amphotericin B colloidal dispersion on renal functions and renal morphology in rats

BACKGROUND AND AIM: Amphotericin B (AmB) desoxycholate remains as one of the most efficacious agents currently available for the treatment of systemic fungal infections; however, amphotericin B colloidal dispersion (ABCD) has been developed because of AmB desoxycholate nephrotoxicity. The goal of our study was to compare the effect of administration of AmB desoxycholate and ABCD on renal functions and renal morphology in rats. RESULTS: Amophotericin B desoxycholate as well as ABCD causes damage to renal tubuli and polyuria. Amophotericin desoxycholate causes considerably more severe damage to tubuli than ABCD, but the morphological damage to renal glomeruli is minimal in both formulas. In tubular cells, AmB desoxycholate causes severe damage to mitochondria, vacuolation of cytoplasm, and increased values of volume density of peroxisomes. CONCLUSION: None of these formulas causes a decrease in glomerular filtration in rats when animals are properly hydrated.