Lakatua D

Circannual Variation of Intestinal Cell Proliferation in Bdf1 Male Mice on Three Lighting Regimens

BDF1 male mice were studied over a 24-hr span in winter, spring, summer and fall. For three weeks prior to study, one-third of the animals were kept under a lighting regimen of 8 hr light alternating with 16 hr of darkness (LD 8:16), one-third on a lighting regimen of LD 12:12 and a remainder on a lighting regimen of LD 16:8. During each study, subgroups of animals on all three lighting regimens were killed at 4-hr intervals over a 24-hr span. Twenty minutes prior to being killed, the animals received 5 microCi of [3H]-thymidine/0.2 ml/20 gm of body weight intraperitoneally. The thymidine uptake in the DNA of the colon and of the small intestine were studied as an index of cell proliferation. A circadian rhythm in [3H]-thymidine uptake in the colon was found and validated by cosinor analysis. This rhythm was similar in acrophase and amplitude in the animals kept on LD 8:16 and LD 12:12. Also in the mice on LD 16:8, there was a statistically significant circadian rhythm of [3H]-thymidine uptake in the DNA of the colon during all four seasons. The acrophases of this rhythm, however, varied widely suggesting free running. A circadian rhythm of [3H]-thymidine uptake in small intestine was less consistent. In animals on all three lighting regimens, however, a circannual variation of [3H]-thymidine uptake in DNA in colon and small intestine was found with the highest uptake during summer. This study indicates that a lighting regimen of LD 16:8 does not reliably synchronize the circadian rhythm of [3H]-thymidine uptake in the colon. It further shows a circannual rhythm of this function in the colon and in the small intestine which persists under three lighting regimens (LD 8:16, 12:12 and 16:8) maintained for three to four weeks prior to being killed.

Circadian as well as circannual rhythms of circulating aldosterone have decreased amplitude in aging women

Age differences in the characteristics of the circadian rhythm in circulating radioim-munoassayable aldosterone were studied on nine 20 to 26 year-old and ten 70 to 78 year-old women and ten 23 to 26 year old and ten 70 to 80 year old men in Würzburg, West Germany. These diurnally active-nocturnally resting subjects were sampled every 3 hours for 15 hours. A classical analysis of variance and a multivariate analysis of rhythm characteristics revealed major effects of age exerted on the circadian aldosterone amplitude in women (p = 0.003) but not in concomitantly sampled men. These observations complement the study of circadian and circannual rhythms in 8 young adults (15–21 years), 10 mature adults (29–36 years) and 10 post-menopausal (44–59 years) North American women, sampled at 100 minute intervals for 24 hours, once in each season, and document that the adrenocortical aldosterone-producing system remains rhythmic with at least two frequencies up to the late decades of human life, although in women it may be characterized by a reduction in the extent of spectral change after 70 years of age.

Observed differences in gentamicin pharmacokinetic parameters and dosage recommendations determined by fluorescent polarization immunoassay and radioimmunoassay methods

Radioimmunoassay (RIA) and fluorescent polarization immunoassay (FPI) methods for quantitative gentamicin serum concentration assay have been shown to be comparable. The purpose of this study was to determine if serum concentration-time data from the same patients assayed by RIA and FPI would provide the same estimates for half-life, elimination rate constant, distribution volume, drug clearance, and gentamicin dose. A total of 99 preand postinfusion serum samples were obtained from 30 patients. Samples were divided and assayed by RIA or FPI, and the resultant serum concentration-time data were fitted to a standard one-compartment model. The correlation between the two assay methods was 0.99 (p < 0.005). A mean difference of 10% was seen in distribution volume, gentamicin clearance, and gentamicin dose from quantitative data from the two methods. These differences were significant (p < 0.01). Although the two methods appear to be interchangeable, based on in vitro comparison, differences in calculated pharmacokinetic parameters resulted in significant differences in dose recommendations.

Circadian Rhythm in Mammary Cytoplasmic Estrogen Receptor Content of Balb/C Female Mice with and Without Pituitary Isografts

Cytoplasmic estrogen receptors were determined by the dextran-coated charcoal method in inguinal breast tissue of three groups of Balb/C female mice 6-8 weeks following subcutaneous implantation into the intact animals of three pituitary glands and three pieces of skeletal muscle (group I), three pituitary glands and three segments of hypothalamic tissue (group II), or three pieces of skeletal muscle (group III) obtained from animals of the same inbred strain as control. A circadian rhythm in estrogen receptor content was statistically quantified by cosinor analysis in the muscle implanted control and the pituitary and hypothalamic implant groups. In the pituitary and muscle implant group the circadian rhythm is of borderline significance with a P-value between 0.05 and 0.10. The timing (acrophase) and extent of change (amplitude) are similar in all three treatment groups. The average receptor content (MESOR) in the two pituitary-implanted groups, which in previous studies were shown to have an increased breast cancer incidence is about twice that of the control group. The reduction in the pituitary induced breast cancer rate by hypothalamic tissue addition to a cancer incidence between the animals with pituitary and muscle isograft and the mice carrying no pituitary at all has also been shown previously in this strain of mice and is not reflected in receptor content.

Comparison of gentamicin pharmacokinetic parameters determined by fluorescence polarization immunoassay and latex agglutination methods

Fluorescence polarization immunoassay (FPIA) (TDx, Abbott Laboratories Diagnostics, Irvin, TX, U.S.A.) is commonly utilized for quantitative determination of gentamicin serum concentrations. Recently, automated homogeneous latex agglutination (LA) (Technicon Immuno-1, Miles Diagnostics Division, Tarrytown, NY, U.S.A.) for the quantitative determination of gentamicin serum concentrations has been approved for commercial use. The purpose of this study was to determine whether gentamicin serum concentration-time data from the same patients assayed by FPIA and LA would produce the same estimates for half-life, elimination rate constant, distribution volume, drug clearance, dosage interval, and dose. A total of 70 pre- and postinfusion serum samples were obtained from 19 patients. Each sample was divided into two aliquots; one was assayed by FPIA and the other by LA. The correlation coefficient between the two assay methods was 0.99 (y = 1.03x – 0.05). The mean differences for half-life, volume of distribution, elimination rate constant, total body clearance, and gentamicin dosage were 0.13, 0.32, 0.66, −0.99, and 0.03%, respectively. No statistically significant differences were seen in calculated gentamicin pharmacokinetic parameters (p < 0.05). Pharmacokinetic parameters and dosage recommendations derived from FPIA and the LA assay using pre- and postinfusion serum concentration-time data appear interchangeable and do not result in differences between gentamicin dosing regimens.

Psychoendocrine Circadian Network of Seven Hormones, Age and Reproductive Stage of Women

Four groups of women (total N=46) gave blood every 20 min (groups 3 & 4) or every 4 hrs (grps 1 & 2) for 24 h in the spring of 1978 and supplied 9 sets of retrospective data regarding earlier vs. later timing of daily habits of waking, retiring, alertness, fitness and best mood. Circadian parameters were determined for prolac tin, progesterone, insulin, cortisol, T4, T3 and renin. Associations were subsequently studied for each group between circadian parameters of different hormones and psychological state parameters. Generally, hormonal acrophases did not predict psychological state, but the usually small-number of subjects (a large number of determinations per subject notwithstanding) mitigates against the demonstrability of any but the most prominent features. Psychoendocrine associations were found for the amplitudes of insulin and renin: women reporting habitually earlier well-being had larger amplitudes. Associations with behavior were also recorded for the mesors of T4, T3, and cortisol. On the average, the prolactin and progesterone mesor and/or amplitude correlated negatively or near zero with the behavioral state marker in the pre-menopausal women, but highly positively in the post-menopausal women, the age differences in p8ychoneuroendocrine correlations being reliable. Major realignments with age and/or reproductive stage characterize the rhythmic psychoneuroendocrine network.