PP104. Pregnancy-induced hypertension is a strong risk factor for hypertension just 5 years after delivery: A double cohort study at the National Center for Child Health and Development and Showa University Hospital, Tokyo.

INTRODUCTION: Pregnancy-induced hypertension (PIH) is associated with increased risk for cardiovascular diseases later in life. OBJECTIVES: To assess the prevalence of subsequent hypertension and other life-style diseases five years after delivery in women who experienced pregnancy- induced hypertension. METHODS: A total of 1527 women who delivered singletons were registered at the National Center for Child Health and Development and Showa University Hospital Mother and child health center of integrated perinatal period between 2003 and 2005. After five years, these women were invited to participate in this study by mail, and 816 women completed the analysis. The women visited our hospital and underwent a medical examination. Women who were pregnant and nursing at the time when the physical examination was conducted were excluded from this survey. The outcomes assessed included the prevalences of hypertension, diabetes, and dyslipidemia. RESULTS: The number of PIH cases was 27 (3.3%: PIH group), whereas 787 women were used as controls subjects. The mean blood pressure five years after delivery was higher in the PIH group than in the control group (91.6±15.5mmHg vs 82.4±8.8mmHg, respectively; p<0.001), and the prevalence of hypertension five years after labor was 18.5% in the PIH group and 2.9% in the controls (odds ratio UOR Y=6.2; 95% confidence interval (CI)=2.2-17.5; p=0.003). Moreover, regarding high-normal blood pressure (>130/85mmHg), the prevalence was 33.4% in the PIH group and 6.1% in the control subjects (OR=7.2; 95% CI=3.1-16.3; p=0.003). No differences in the prevalences of subsequent diabetes or dyslipidemia were observed. CONCLUSION: Five years after the index pregnancy, women who experienced PIH exhibit an increased risk for subsequent hypertension. Therefore, the blood pressure of women with history of PIH should be regularly monitored after delivery.

Three-dimensional distribution of astrocytes in zebrafish spinal cord.

We prepared a monoclonal antibody (A-22) that recognizes a 60-kDa protein in the zebrafish brain. The antigen is distributed throughout the brain but is not found outside it. The antibody recognizes star-shaped cells with long processes in the spinal cord. All A-22-positive cells are also GFAP-immunopositive, but there are GFAP-positive cells that are A-22-negative. The cells are connected to small veins and to the surface of the spinal cord. Immunopositive cells are generally homogeneous in size and shape and are found not only in the spinal cord but also in several areas of the brain. These results indicate that the stained cell is an astrocyte. Most of these cells (88%) are distributed in the gray matter of the spinal cord; the remainder (12%) are found in the white matter. Most of the cells in the gray matter are found in the ventral and dorsal horns, but some are also present in the central area along the ventricle. Glial cell bodies form an array along the longitudinal axis and are connected to each other by thick projections. The cellular array is not visible in coronal sections. In contrast, thin processes from the cells extend to the surfaces of veins, to neurons, and to the periphery of the spinal cord. We estimate that there are about 13,500 A-22-positive astrocytes in the spinal cord; however, this represents only 26% of the total number of astrocytes in the spinal cord (approximately 52,000).

Chronopharmacology of granulocyte colony-stimulating factor in mice.

The role of the sensitivity of bone marrow cells to, and the pharmacokinetics of granulocyte colony-stimulating factor (G-CSF) on the rhythm of leukocyte-increasing effect was investigated in ICR male mice housed under a standardized light-dark cycle (lights on at 0700, off at 1900). A significant circadian rhythm was demonstrated for leukocyte counts at 24 hr after G-CSF (250 microg/kg, s.c.) injection at six different circadian times (P < .01). The leukocyte counts of mice given G-CSF at 0500, 0900, 1300 or 1700 were significantly higher than those of mice given G-CSF at 2100 (P < .01, respectively). The rhythmic pattern resembled overall the rhythm occurring after saline injection. In the comparison between leukocyte counts after G-CSF injection at 0700 and 1900, the time when leukocyte counts are equal in nondrugged state, the leukocyte counts at 24 hr after G-CSF (250 microg/kg, i.v.) injection were approximately 50% higher in mice injected with the drug at 0700 than at 1900 (P < .01). Bone marrow cultures obtained at two times of day resulted in different numbers of myeloid colonies even when treated with the same concentrations of G-CSF in vitro. The colony-forming activity of G-CSF was significantly more potent at 0700 than at 1900 (P < .01). The plasma G-CSF concentrations after G-CSF (250 or 5 microg/kg, i.v.) injection were significantly higher in mice receiving injections with the drug at 0700 than at 1900 (P < .05, respectively). The area under the curve and mean residence time were significantly larger in mice injected with the drug at 0700 than at 1900 (P < .01, P < .05, respectively). Our suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to, and the pharmacokinetics of the drug.

Influence of dosing time on pharmacological action of G-CSF in mice.

The role of the susceptibility of living organisms and the pharmacokinetics of G-CSF on the rhythm of granulocyte colony-stimulating factor (G-CSF) activity was investigated. ICR male mice were housed in a standardized light-dark cycle (lights on at 0700, off at 1900) with food and water ad libitum. The leukocyte counts at 2 and 24 hr after G-CSF (250 microg/kg, i.v.) injection were significantly higher in mice injected with the drug at 0700 than at 1900 (p<0.01, respectively). The higher leukocyte-increasing effect corresponded to drug dosing at the time in which the granulocyte colony formation stimulated by G-CSF and DNA synthesis increased and the lower effect corresponded to drug dosing at the time in which they decreased. The rhythmicity corresponded to that in plasma G-CSF concentration. The present study suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to the drug and the pharmacokinetics of the drug.

Bone mineral density after surgical treatment for Graves' disease.

Restoration of bone loss associated with thyrotoxicosis follows normalization of thyroid function. However, the extent of bone loss and restoration remain controversial. To clarify whether bone recovery is complete, we examined lumbar and femoral bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) in 14 thyrotoxic premenopausal women with Graves' disease and 31 premenopausal women treated for Graves' disease by subtotal thyroidectomy who had been in remission for at least 3 years. In the remission group, to exclude the influence of subclinical hyperthyroidism, thyrotropin (TSH) levels were followed and subjects with low levels excluded. Thus, all 31 subjects had normal thyroid hormone levels with transiently or persistently elevated TSH levels post-thyroidectomy. Data from the two study groups were compared with those from healthy premenopausal controls matched for age, height and weight. Mean lumbar (anterior-posterior and lateral), femoral neck, and trochanter BMDs were significantly lower in the thyrotoxic group than in controls (p < .05, all four BMDs). Mean lumbar (anterior-posterior), femoral neck and trochanter BMDs were significantly higher in the remission group than in controls (p < 0.05, all three BMDs). At the time of DXA, the 31 remission subjects showed a significant positive correlation between lumbar BMD and TSH (p < 0.05) and a significant negative correlation between femoral neck BMD and free triiodothyronine (FT3) (p < 0.05). These observations suggest: (1) in premenopausal women, bone loss associated with thyrotoxicosis due to Graves' disease is present but is fully restored when remission is reached after subtotal thyroidectomy; (2) subclinical hypothyroidism after subtotal thyroidectomy may result in higher BMD than that of controls.