To investigate the underlying causes for aldose reductase deficiency-induced diabetes insipidus, we carried out studies with three genotypic groups of mice. These included wild-type mice, knockout mice, and a newly created bitransgenic line that was homozygous for both the aldose reductase null mutation and an aldose reductase knockin transgene driven by the kidney-specific cadherin promoter to direct transgene expression in the collecting tubule epithelial cells. We found that from early renal developmental stages onward, urine osmolality did not exceed 1,000 mosmol/kgH2O in aldose reductase-deficient mice. The functional defects were correlated with significant renal cellular and structural abnormalities that included cell shrinkage, apoptosis, disorganized tubular and vascular structures, and segmental atrophy. In contrast, the transgenic aldose reductase expression in the bitransgenic mice largely but incompletely rescued urine concentrating capacity and significantly improved renal cell survival, cellular morphology, and renal structures. Together, these results suggest that aldose reductase not only plays important roles in osmoregulation and medullary cell survival but may also be essential for the full maturation of the urine concentrating mechanism.

The association between the onset of depressive illness and the paramenstruum has been reported. In the present study, we looked at changes in platelet 5-HT uptake in six healthy, regularly menstruating subjects on days 1, 10, and 24 of three consecutive menstrual cycles to explore possible biochemical bases for mood changes associated with menstruation. Platelet 5-hydroxytryptamine (5-HT) uptake was determined by suspension of platelet pellets in 0.5-5 microM hydroxy [G-3H] tryptamine [( 3H]-5-HT) creatinine sulfate solution at 37 degrees C and measurement of radioactivity of [3H]-5-HT in the platelets using liquid scintillation counting. Mood changes were measured using the Moos Menstruation Distress Questionnaire and the Spielberger State Anxiety Scale. Analysis of variance and trend analysis revealed significant elevation of Km and Vmax on day 24 of the cycle, which was consistent across the three menstrual cycles studied. A significant linear rise of "negative affect" across each cycle peaking on day 1 was detected. "Water retention" and "behavioral change" also peaked on day 1. No significant correlation, however, was obtained between the mood scores and platelet 5-HT uptake. These findings are discussed.

No abstract