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Biomedical subjects

J Bunn

Publications and source records attributed to J Bunn.

14 recordsLinked to original sources

Can maternal depression increase infant risk of illness and growth impairment in developing countries?

Despite relative improvement in living conditions and availability of modern healthcare, infant mortality rates continue to be very high in many developing countries. High rates of depression have also been reported in women in these countries. The continuous care and attention of children is a demanding task, and poor physical or mental health in mothers might be expected to have adverse consequences on their children's health, nutrition and psychological well-being. Review of published literature reveals very little research in developing countries on the association between poor mental health in mothers and the subsequent physical well-being of their children. We hypothesize that the level of care provided by mothers with depression may put their infants at higher risk of infection and impaired growth, compared with infants of mothers without depression. We outline approaches to test such a hypothesis in a developing country, and discuss its implications.

Adult↗

The inhibition of growth and down-regulation of gonadotropin releasing hormone (GnRH) receptor in alphaT3-1 cells by GnRH agonist.

Gonadotropin releasing hormone (GnRH) and its analogs inhibit the growth of hormone-dependent tumors in vivo and in vitro. The inhibition of growth and proliferation of tumor cells in vitro by GnRH and its analogs indicates that the tumor suppressing effect of the hormone is only partially due to suppression of pituitary gonadotropin release which reduces circulating steroid levels that are required for proliferation. Demonstration of GnRH-binding sites on some tumors suggests a direct inhibitory effect of GnRH and its analogs. However, the mechanism by which GnRH and its analogs inhibit tumor cell growth is not known. Our hypothesis is that the inhibition of growth and proliferation of tumor cells by GnRH and its analogs are mediated through down-regulation of its receptor expression. To test this hypothesis, mouse pituitary gonadotrope cell line (alphaT3-1) was selected as a model since this is the only cell line which expresses a sufficiently high level of GnRH receptors for precise measurements of the mRNA for the receptor. Addition of GnRH agonist (D-Lys6)GnRH to the cell cultures caused a time-dependent decrease in both cell growth, as measured by cell number, and cell proliferation, as measured by [3H]thymidine incorporation into DNA. After 1 h of treatment of alphaT3-1 cells with 1 microM of (D-Lys6)GnRH, the cell number was reduced to 83.0 +/- 13.4 compared to control, decreased to 75.1 +/- 3.2 at 2 h, 63.2 +/- 0.66 at 4 h and 52.2 +/- 0.87 at 24 h. This decrease in cell number was accompanied by a parallel decrease in [3H]thymidine incorporation into DNA. The inhibition of cell growth and [3H]thymidine incorporation by treatment with 1 microM of (D-Lys6)GnRH was sustained for at least 72 h. Inhibition of alphaT3-1 cell growth and [3H]thymidine incorporation was dose-dependent; thus 10(-9) M (D-Lys6)GnRH resulted in about 30% inhibition within 4h which was comparable to 10(-6) M (D-Lys6)GnRH, whereas 10(-12) M (D-Lys6)GnRH was ineffective. Measurement of mRNA for the GnRH receptor by Northern blot analysis showed a decrease in levels of mRNA by 5% within 2 h of treatment of alphaT3-1 cells with 1 microM (D-Lys6)GnRH, by 30% at 4 h and by 50% at 24 h. In conclusion these data demonstrate that treatment of alphaT3-1 cells with (D-Lys6)GnRH causes an inhibition of cell growth and proliferation, and down-regulates the GnRH receptor mRNA levels.

Animals↗

Effect of leukotriene inhibitor on salicylate induced morphologic changes of isolated cochlear outer hair cells.

Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Other studies have demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in isolated cochlear outer hair cells (OHCs), and decreased otoacoustic emission. We have shown that pretreatment with an LT inhibitor prevents salicylate induced hearing loss, a decrease in cochlear blood flow and changes in otoacoustic emissions. The objectives of the current study were to determine the effect of exposure of salicylate and LTs on the morphology of isolated OHSc and to determine the effect of LT inhibitors on salicylate induced morphologic changes of isolated OHCs. Isolated OHCs from chinchilla cochlea were exposed to different test solutions. The groups included sodium salicylate (10 mM) with or without pretreatment with an LT inhibitor (L-663, 536, 30 microM), 0.1 or 1.0 microM solution of LTC4, LTD4, LTE4, and two control solutions, standard bathing solution (SBS) or leukotriene inhibitor alone. Osomolality of all solutions were kept at 305 +/- 5 mmolkg-1. The OHCs were observed under an inverted microscope. Images were stored onto a computer and analyzed later. OHCs exposed to the salicyalate developed a decrease in mean cell length. The exposure of OHCs to LTC4, LTD4, and LTE4 also demonstrated a similar decrease in mean cell length. Cells in the control SBS or LT inhibitor alone groups did not show any change. OHCs exposed to salicylate in the presence of the LT inhibitor did not exhibit morphologic changes. This study suggest that arachidonic acid metabolites, especially an increase in the concentration of LTs, seem to play an important role in the pathogenesis of salicylate ototoxicity.

Animals↗

Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages.

In 1984, all non-immune children under the age of 5 years in the Gambian villages of Keneba and Manduar were vaccinated against hepatitis B virus (HBV). All children born in these villages since 1984 have been vaccinated in infancy. Despite a rapid fall in antibody concentrations, vaccine efficacy against HBV infection and chronic carriage of HBsAg has increased with time. Overall, vaccine efficacies in 1993 against HBV infection and chronic HBsAg carriage were 94.7% (95% Cl 93.0-96.0) and 95.3% (91.0-97.5), respectively. Breakthrough infections in vaccinated children largely originate from chronic HBsAg carriers. Thus, we tested 261 chronic carriers for HBV DNA and e antigen. The prevalence of these markers of infectivity, and the amount of HBV DNA, decreased greatly with age. Detailed studies of breakthrough infections over two 4-year periods revealed that in the second period there were fewer than half the expected numbers of infections. Our findings suggest that in Keneba and Manduar long-term vaccination is progressively decreasing HBV transmission by chronic carriers, since their infectivity diminishes with time.

Adolescent↗