Spermicidal activity of oxovanadium(IV) complexes of 1, 10-phenanthroline, 2,2'-bipyridyl, 5'-bromo-2'-hydroxyacetophenone and derivatives in humans

We have recently reported that tetrahedral metallocene complexes containing vanadium(IV) (vanadocene) have potent spermicidal activity against human sperm. The spermicidal activity was dependent on vanadium(IV) as the central metal ion within the bis-cyclopentadienyl (Cp2)-metal complex, but the variation of diacido groups and/or replacement with bidentate ligands coordinated to the Cp2-vanadium(IV) moiety also significantly modulated the spermicidal potency. To assess the structure-activity relationship between vanadocenes and other coordination complexes of vanadium(IV), a set of 11 oxovanadium(IV) complexes with different geometrical configurations were synthesized and evaluated for spermicidal activity by computer-assisted sperm analysis. These complexes included mono and bis ancillary ligands, 1,10-phenanthroline (phen): [VO(phen), VO(phen)2, VO(Me2-phen), VO(Me2-phen)2, VO(Cl-phen), and VO(Cl-phen)2]; 2,2'-bipyridyl (bipy): [VO(bipy), VO(bipy)2, VO(Me2-bipy), and VO(Me2-bipy)2], linked via nitrogen atoms; and 5'-bromo-2'-hydroxyacetophenone (acph): [VO(Br,OH-acph)2], linked via oxygen donor atoms. All 11 oxovanadium(IV) complexes elicited concentration-dependent spermicidal activity at micromolar concentrations (EC50 values: 5.5-118 microM). The bis-phenanthroline complex of oxovanadium(IV), VO(Cl-phen)2, was the most active, and the mono bipyridyl complex, VO(bipy), was the least active; the order of efficacy was VO(Cl-phen)2 > VO(phen)2 > VO(Br,OH-acph)2 > VO(Me2-phen) > VO(bipy)2 > VO(phen) > VO(Cl-phen) > VO(Me2-phen)2 > VO(Me2-bipy)2 > VO(Me2-bipy) > VO(bipy). The neutral complex, VO(Br, OH-acph)2, induced rapid sperm immobilization (T1/2 = 38 sec). The sperm-immobilizing activity of mono- and bis-ligated oxovanadium(IV) complexes was irreversible, since the treated sperm underwent apoptosis, as determined by the flow cytometric quantitation of mitochondrial membrane potential, surface Annexin V binding assay, and in situ DNA nick-end labeling of sperm nuclei. The percentages of apoptotic sperm quantitated by the flow cytometric assay correlated well with the spermicidal potency of oxovanadium(IV) complexes. These results provide unprecedented evidence that the spermicidal and apoptosis-inducing activities of vanadium(IV) complexes are determined by the oxidation state of vanadium as well as their geometry. Because of its rapid and potent sperm-immobilizing activity, the bromo-hydroxyacetophenone complex, [VO(Br,OH-acph)2], may be useful as a contraceptive agent.     

Predicting psychiatric admission from an emergency room. Psychiatric, psychosocial, and methodological factors

The determinants of psychiatric hospitalization, especially nonspecific issues, have been studied extensively. The methodological problem of correlational non-cross-validated findings are seen as contributing to our uncertainties about the critical issues involved in the decision to admit. A cross-validated multiple regression analysis of determinants of hospitalization in an inner-city municipal hospital revealed two determinants of hospitalization: severity of schizophrenic symptoms and active suicidal and/or homicidal ideation. They accounted for one third of the variance without shrinkage. Quasi-experimental designs may be the most efficient means of studying the remaining unexplained variance.     

Serologic and hematologic values of wild coyotes in Wisconsin

Blood samples were obtained from 30 coyotes (Canis latrans) captured in northern Wisconsin in conjunction with radio-telemetry studies. Samples were assayed for seven hematologic values, seven serum chemistries, serum albumin, globulin and total protein. Results are given with respect to sex and age and are compared with available data for captive wild and pen-raised coyotes. Leukocyte counts were greater for males than females and packed cell volumes were greater for adults than young, possibly due to differential response to capture and handling stress. Hemoglobin concentrations and calcium levels suggest differences in nutrition between pen-raised and wild coyotes. Sex and age differences in serum calcium for wild coyotes probably reflect nutritional differences between groups examined. Juvenile coyote serum alkaline phosphatase levels declined curvilinearly with age for coyotes less than one year old, suggesting a possible technique for separating juveniles and yearlings captured in autumn that are released for research purposes. Elevated glucose levels and leukocyte counts in wild coyotes may reflect greater handling stress than for pen-raised and captive coyotes. No significant sex or age effects were found for levels of serum urea nitrogen, total protein, cholesterol, and total bilirubin.     

Fat cell number and weight gain in lithium treated patients

Total amount of fat, fat cell size, and fat cell number were determined in 33 patients under long-term lithium treatment. The weight gain during the treatment was estimated both by the patients themselves (questionnaire) and from their records. A positive correlation between fat cell number and weight gain was found whereas the fat cell size showed no correlation to weight gain.     

Lithium effects on diurnal rhythm of calcium, magnesium, and phosphate metabolism in manic-melancholic disorder

The diurnal rhythm of plasma phosphate, calcium, and magnesium was studied in 34 lithium treated patients, in 42 other psychiatric patients, and in 47 healthy persons. Seventeen blood samples were drawn from each person during the 24-hour period. Lithium was given at 10 p.m. and in the next few hours plasma phosphate decreased compared with the two control groups. In the same period plasma calcium showed a temporary increase, whereas plasma magnesium was increased during the whole 24-hour period. The lithium treated patients had a reduced urinary calcium excretion during the night, and an increased urinary magnesium excretion during the day, whereas no changes were found in urinary phosphate excretion.     

Effect of interleukin 1 and leukaemia inhibitory factor on chondrocyte metabolism in articular cartilage from normal and interleukin-6-deficient mice: role of nitric oxide and IL-6 in the suppression of proteoglycan synthesis

We studied the role of IL-6 and nitric oxide (NO) in IL-1 and leukaemia inhibitory factor (LIF) induced suppression of proteoglycan synthesis. Cartilage explants of patellae and femoral heads were incubated with IL-1 or LIF. Conditioned media were analysed for IL-6 activity (B9-assay) and NO content (Griess). Proteoglycan synthesis was assessed using [35S]sulfate incorporation. IL-1 dose dependently induced IL-6 synthesis and neutralizing IL-6 with antibodies did not reduce proteoglycan synthesis suppression, neither in explants nor in isolated chondrocytes. IL-6 independence was confirmed using cartilage from IL-6 deficient mice. IL-1 significantly increased NO release in normal and IL-6 deficient chondrocytes and addition of the NO synthase inhibitor, N(G)-monomethyl-L-arginine markedly alleviated proteoglycan synthesis suppression. LIF also induced proteoglycan synthesis suppression in cartilage from normal and IL-6 deficient mice, but the suppression was neither accompanied by nor dependent on NO release. Furthermore, proteoglycan synthesis suppression during experimental arthritis was similar in both normal and IL-6 deficient mice. We concluded that IL-6 is not a necessary cofactor in IL-1 and LIF induced suppression of proteoglycan synthesis. Furthermore, only the IL-1 induced suppression was mediated by NO, suggesting that inhibition of proteoglycan synthesis may occur through different pathways.     

Photoimmunodetection: a nonradioactive labeling and detection method for DNA

We describe a simple detection system for DNA based on antibody detection of UV-induced photoproducts. It includes a convenient and inexpensive labeling procedure, which is completed in 5-10 min. The only equipment required is a UV source such as an ordinary transilluminator or a DNA crosslinker. Using a monoclonal antibody specific for thymine dimers, coupled to horseradish peroxidase, we are able to detect subpicogram amounts of UV-irradiated DNA directly, and approximately 10 pg homologues DNA indirectly by hybridization with an irradiated probe.