Comparison of in vivo and in vitro percutaneous absorption of T-2 toxin in guinea pigs

The fate and distribution of T-2 were examined in 6 guinea pigs. T-2 (1.2 micrograms/cm2), in methanol or DMSO, was painted onto the shaved backs of guinea pigs, a screen barrier was applied, urine and feces were collected daily and the guinea pigs were killed after 48 hr. Disks of skin (lateral to the in vivo site of application) were excised from the guinea pigs and used for in vitro penetration studies with static diffusion cells. Skin excised from 6 additional guinea pigs was used for penetration studies with flow-through diffusion cells. For in vitro studies, T-2 dissolved in methanol or DMSO was applied to the epidermal surfaces and the appearance of penetrant in receptor fluid bathing the dermal surfaces was monitored for 48 hr. Metabolism of T-2 was measured by using thin layer radiochromatography to identify metabolites. In the in vivo study, mean cutaneous absorption (n = 3) after 48 hr (expressed as per cent dose) was 22.5 and 51.9 for the methanol and DMSO groups, respectively. In vitro cutaneous penetration for static diffusion cells was 3.9 and 38.4 for the methanol and DMSO groups. For flow-through diffusion cells, mean penetration (n = 9) was 14.6 and 42.6 for the methanol and DMSO groups. Urinary metabolites of T-2 were T-2 triol, 3' OH-HT-2, T-2 tetraol, the glucuronide conjugate of HT-2 and several more polar metabolites. The main metabolite of T-2 in the receptor fluid bathing the dermal surfaces of excised skin was HT-2.     

Size-fractionated heparins have differential effects on human neutrophil function in vitro

BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.     

Mental disorders into adulthood among adolescents placed in residential care: A prospective 10-year follow-up study

BackgroundChild welfare and juvenile justice placed youths show high levels of psychosocial burden and high rates of mental disorders. It remains unclear how mental disorders develop into adulthood in these populations. The aim was to present the rates of mental disorders in adolescence and adulthood in child welfare and juvenile justice samples and to examine their mental health trajectories from adolescence into adulthood.MethodsSeventy adolescents in shared residential care, placed by child welfare (n = 52, mean age = 15 years) or juvenile justice (n = 18, mean age = 17 years) authorities, were followed up into adulthood (child welfare: mean age = 25 years; juvenile justice: mean age = 27 years). Mental disorders were assessed based on the International Classification of Diseases 10th Revision diagnoses at baseline and at follow-up. Epidemiological information on mental disorders was presented for each group. Bivariate correlations and structural equation modeling for the relationship of mental disorders were performed.ResultsIn the total sample, prevalence rates of 73% and 86% for any mental disorder were found in adolescence (child welfare: 70%; juvenile justice: 83%) and adulthood (child welfare: 83%; juvenile justice: 94%) respectively. General psychopathology was found to be stable from adolescence into adulthood in both samples.ConclusionsOur findings showed high prevalence rates and a high stability of general psychopathology into adulthood among child welfare and juvenile justice adolescents in Swiss residential care. Therefore, continuity of mental health care and well-prepared transitions into adulthood for such individuals is highly warranted.     

Triangulo-{ErIII3} complex showing field supported slow magnetic relaxation

The triangulo-{Er₃} complex [Er₃Cl(o-van)₃(OH)₂(H₂O)₅]Cl₃·nH₂O (n = 9.4; H(o-van) = o-vanillin) (1) was generated by an in situ method. The isolated Er(iii) complex 1 was characterized by elemental analysis and molecular spectroscopy. The results of single crystal X-ray diffraction studies have shown that 1 is built up of trinuclear [Er₃Cl(o-van)₃(OH)₂(H₂O)₅]³⁺ complex cations, chloride anions and water solvate molecules. Within the complex cation the three Er(iii) central atoms are placed at the apexes of a triangle which are bridged by three (o-van)⁻ ligands with additional chelating functions and two μ₃-OH⁻ ligands. Additionally five aqua and one chlorido ligands complete the octa-coordination of the three Er(iii) atoms. AC susceptibility measurements reveal that the compound exhibits slow magnetic relaxation with two relaxation modes.

The triangulo-{Er₃} complex [Er₃Cl(o-van)₃(OH)₂(H₂O)₅]Cl₃·nH₂O (n = 9.4; H(o-van) = o-vanillin) (1) was generated by an in situ method.     

Aerucyclamides A and B: isolation and synthesis of toxic ribosomal heterocyclic peptides from the cyanobacterium Microcystis aeruginosa PCC 7806

Two new modified hexacyclopeptides, aerucyclamides A and B, were isolated from the toxic freshwater cyanobacterium Microcystis aeruginosa PCC 7806. The constitution was assigned by spectroscopic methods, and the configuration determined by chemical degradation and analysis by Marfey's method combined with chemical synthesis. Synthetic aerucyclamide B was obtained through oxidation of aerucyclamide A (MnO2, benzene). The aerucyclamides were found to be toxic to the freshwater crustacean Thamnocephalus platyurus, exhibiting LC50 values for congeners A and B of 30.5 and 33.8 microM, respectively.     

CHANGES IN THE PLASMA PROTEIN PATTERN (TISELIUS ELECTROPHORETIC TECHNIC) OF PATIENTS WITH HYPERTENSION AND DOGS WITH EXPERIMENTAL RENAL HYPERTENSION

The plasma protein pattern of patients with uncomplicated essential hypertension showed only slight variations from the normal while that of patients with severely malignant hypertension showed marked shifts. The fibrinogen and β-globulins were usually elevated beyond the normal range and the albumin decreased. In less severely malignant hypertension, the changes were less marked. In dogs with experimental renal hypertension, the γ-globulin level was greatly elevated, and in one animal exhibiting the malignant syndrome β-globulin and fibrinogen were also increased. Elevation of β-globulin seems in some manner associated with the occurrence of severe vascular disease.