Mos Of Age Research Articles

The role of the renal sympathetic nerves in a model of postmenopausal hypertension

The mechanisms responsible for the increase in blood pressure (BP) in postmenopausal women are unknown. Our preliminary studies suggest that the sympathetic nervous system may contribute to the hypertension (HT) in aging female SHR. The aim of this study was to determine whether the renal nerves contribute to HT in old and young female SHR. Female SHR (18 and 3 mos of age, respectively, n=4/grp) underwent uninephrectomy, and two weeks later, underwent unilateral renal denervation (O‐RD and Y‐RD) or sham surgery (O‐S and Y‐S) and telemetry transmitter implantation. After two weeks recovery, mean arterial pressure (MAP) and heart rate (HR) were recorded for 5 days. MAP was higher in O‐S than other groups (O‐S:167.5±2.4 vs O‐RD:138±2.7 mmHg; p<0.001; and Y‐S:140.6±6.3 vs Y‐RD:122.1±3.9 mmHg, p<0.001). The reduction in MAP after denervation was greater in O‐RD (O‐RD:29.5±0.5 mmHg, vs Y‐RD:17.0±0.9 mmHg, p<0.001). Renal NE content was significantly decreased compared to shams (O‐S: 201.1±30.3 pg/mg vs O‐RD: 35.6±10.3 pg/mg wet weight, p<0.001; and Y‐S:239±24.5 pg/mg vs Y‐RD:18.1±11.4 pg/mg wet weight, p<0.001). These data indicate that the renal nerves play a key role in the control of BP in pre‐ and post‐cycling SHR. The data also suggest that the renal nerves contribute to HT more in old females than young.

Abstract P335: Is GSK-3α a Regulator of Aging?

The glycogen synthase kinase-3 (GSK-3) family of protein kinases consists of two highly related isoforms, α and β. The GSK-3 family has been reported to regulate an astonishing variety of physiological and pathophysiological processes, whereas virtually nothing is known as for whether they regulate aging. Aging, defined as the progressive loss of function accompanied by decreasing fertility and increasing mortality with advancing age, is a complex biological process, controlled by multiple genetic, epigenetic and environmental factors. We now present the first studies defining the role of GSK-3α in the aging process using germline GSK-3α knockout (KO) mice at age of 3, 6, 12, and 24 mos. Age-matched wildtype (WT) mice served as control. Kaplan-Meier analysis shows that percent survivals (WT vs. KO) was 73.33 vs. 42.11 ‡ at 24 mos of age. In the heart we find cardiac hypertrophy, marked cell loss with replacement fibrosis, contractile dysfunction with profound abnormalities of mitochondrial structure, and impaired autophagy (assessed by Beclin1/ATG6), all becoming evident after 6 mos of age. Echocardiographic LV mass (in mg) is as follows (4 time points): 124.0±3.15 vs. 132.4±3.93, 136.2±4.75 vs. 171.5±7.57 ‡ , 169.2±8.53 vs. 203.5±8.18 ‡ , 195.4±9.82 vs. 257.4±7.24 ‡ ; ejection factor: 60.6±1.08 vs. 62.5±1.52, 64.3±1.10 vs. 60.7±1.61*, 58.5±1.74 vs. 52.2±1.41 ‡ , 55.5±0.96 vs. 49.4±1.02 ‡ ; invasive hemodynamic dP/dt+: 6863.8±673.8 vs. 6999.4±473.2, 7115.4±392.9 vs. 6012.6±407.3*, 7509.6±419.6 vs. 4291.6±473.5*, 6889.0±460.9 vs. 3955.5±306.9 ‡ . We also observed increased BrdU positive nuclei in isolated cardiomyocytes from the KO at 6 mos of age, and increased stem cells at every time-point, compared with age-matched WT. In the small intestine, we find marked senescence-associated β-galactosidase (SA-β-GAL) activity associated with thinning of the crypts, consistent with reduced cell cycling in this tissue. The results imply accelerated development of age-related pathologies in the KO heart and small bowel. These phenotypes are associated with a reduced lifespan in the mouse. Thus GSK-3α is a novel regulator of aging which retards age-related pathologies and prolongs lifespan of the organism. (*, P<0.05; ‡, P<0.01 KO vs. WT)

Mouse models of accelerated lenticular aging by carbonyl and oxidant stress

AbstractPurpose Age‐related human cataracts form as a result combined of carbonyl and oxidant stress and other crystallin modifications that destabilize their chaperone function. However, without appropriate models it has been very difficult to demonstrate cause‐and effect and implicate protein modifications in the disease process. To test the role of vitamin C oxidation products (carbonyl stress) and protein oxidation in the formation of crystallin aggregates, we have generated two types of mice that exhibit rapid protein damage.Methods The first model of increased carbonyl stress is the hSVCT2 mouse in which we overexpressed the human vitamin C two transporter under control of the mouse alphaB‐crystallin promoter. (Fan et al. PNAS 2006). The second model of increased protein oxidation is the LEGSKO (Lens Glutathione Synthesis Conditional Knockout mouse) in which we conditionally knocked out gamma‐glutamyl cysteine ligase (Gclc) in order to mimic the low GSH levels of the old lens nucleus.Results Gamma glutamyl cysteine ligase mRNA, activity and glutathione (GSH) levels are severely depressed in the lens of the homozygous mouse, but not in the heterozygous mouse. GSSG/GSH ratio, methionine oxidation and protein disulfide formation are increased at 6 mos of age. Nuclear opacities turn into full nuclear cataracts at 6 mos. Protein disulfide formation reveals a shift from intra‐ to interdisulfide bonds similar to aging human lens. Dramatic upregulation of several candidate transporters is noted.Conclusion Availability of two mice strains with increased carbonyl and oxidative stress, respectively, will allow us to test the hypothesis that rapid modification of crystallins predisposes to protein aggregation and cataractogenesis when bred together. It will also help us develop drugs that slow down the progression of cataractogenesis and study molecular events that precede cataract formation.

Assessment of Circadian Rhythms of Both Skin Temperature and Motor Activity in Infants During the First 6 Months of Life

The authors developed a method useful for home measurement of temperature, activity, and sleep rhythms in infants under normal-living conditions during their first 6 mos of life. In addition, parametric and nonparametric tests for assessing circadian system maturation in these infants were compared. Anthropometric parameters plus ankle skin temperature and activity were evaluated in 10 infants by means of two data loggers, Termochron iButton (DS1291H, Maxim Integrated Products, Sunnyvale, CA) for temperature and HOBO Pendant G (Hobo Pendant G Acceleration, UA-004-64, Onset Computer Corporation, Bourne, MA) for motor activity, located in special baby socks specifically designed for the study. Skin temperature and motor activity were recorded over 3 consecutive days at 15 days, 1, 3, and 6 mos of age. Circadian rhythms of skin temperature and motor activity appeared at 3 mos in most babies. Mean skin temperature decreased significantly by 3 mos of life relative to previous measurements (p = .0001), whereas mean activity continued to increase during the first 6 mos. For most of the parameters analyzed, statistically significant changes occurred at 3–6 mos relative to 0.5–1 mo of age. Major differences were found using nonparametric tests. Intradaily variability in motor activity decreased significantly at 6 mos of age relative to previous measurements, and followed a similar trend for temperature; interdaily stability increased significantly at 6 mos of age relative to previous measurements for both variables; relative amplitude increased significantly at 6 mos for temperature and at 3 mos for activity, both with respect to previous measurements. A high degree of correlation was found between chronobiological parametric and nonparametric tests for mean and mesor and also for relative amplitude versus the cosinor-derived amplitude. However, the correlation between parametric and nonparametric equivalent indices (acrophase and midpoint of M5, interdaily stability and Rayleigh test, or intradaily variability and P1/Pultradian) despite being significant, was lower for both temperature and activity. The circadian function index (CFI index), based on the integrated variable temperature-activity, increased gradually with age and was statistically significant at 6 mos of age. At 6 mos, 90% of the infants' rest period coincided with the standard sleep period of their parents, defined from 23:00 to 07:00 h (dichotomic index I < O; when I < O = 100%, there is a complete coincidence between infant nocturnal rest period and the standard rest period), whereas at 15 days of life the coincidence was only 75%. The combination of thermometry and actimetry using data loggers placed in infants' socks is a reliable method for assessing both variables and also sleep rhythms in infants under ambulatory conditions, with minimal disturbance. Using this methodological approach, circadian rhythms of skin temperature and motor activity appeared by 3 mos in most babies. Nonparametric tests provided more reliable information than cosinor analysis for circadian rhythm assessment in infants. (Author correspondence: elvirada@um.es)

Prevalence of vitamin D deficiency among healthy infants in Sacramento, CA

Concern about vitamin D deficiency in infants and children has recently increased. We conducted a one year study to determine the prevalence of vitamin D deficiency in infants 6â18 mos of age in Sacramento, CA and to identify dietary and lifestyle risk factors for deficiency. 178 healthy infants seen at the pediatric clinic at UC Davis Medical Center were recruited 8/06-8/07. Demographic, lifestyle, and dietary data were collected and plasma 25(OH) vitamin D (25OHD) concentrations were measured by radioimmunoassay. The mean ± SD concentration for all infants was 94 ± 40 nmol/L. 9% (16/178) were found to be deficient (<50 nmol/L), 69% (11) of whom were currently breastfed. 28% (11/40) of all infants receiving breast milk were deficient. Exclusively breastfed infants (no other milk source) had significantly lower 25OHD levels (64 ± 41 nmol/L) than infants not currently breastfed and receiving milk, formula, or both (103 ± 37 nmol/L; p < 0.05). 12.5% (5/40) of breastfed infants reported taking vitamin D supplements. Significant differences were not seen based on sun exposure or race/ethnicity. These results suggest 25OHD values in infants 6â19 mos of age are most strongly determined by infant feeding practices and usual predictors for vitamin D status in adults such as seasonality, ethnicity, and sun exposure are less important. Vitamin D supplements are recommended for exclusively breastfed infants by two months of age. These data suggest that increased attention to this recommendation may decrease the prevalence of vitamin D deficiency in this population of infants.

Effect of ovariectomy in the renal effects of NFkB inhibition on aged DOCA hypertensive female

The loss of ovarian function with aging is associated with increases in BP and renal dysfunction. Mineralocorticoid hypertension (DOCA) is associated with increased NF‐kB activation that regulates genes involved in BP and renal function regulation. Young female (F) DOCA rats exhibit hypertension and renal injury that is exacerbated after ovariectomy (ovx). Since NFkB inhibition lowered BP in male DOCA rat, we hypothesize that NFkB inhibition will attenuate the development of hypertension and renal damage in old ovx DOCA in a greater extent than in old F‐DOCA rats. F‐DOCA rats were ovx or sham operated at 9 mos of age and treated with NFkB inhibitor (PDTC) for 2 weeks. Ovx at 9 mos did not alter BP (F: 147.1 ± 4.2 vs Ovx: 145.4 ± 5.1mmHg) but increased glomerular filtration rate (GFR), and decreased renal vascular resistance (RVR) and proteinuria. Blockade of NFkB increased GFR (1.32 ± 0.1 vs 1.6 ± 0.1 ml/min/g) and decreased RVR and P in female (29.9 ± 0.8 vs 16.6 ± 1.5ml/min/g and 14.1 ± 0.3 vs 2.5 ± 1.0g/ml); however it decreased GFR (1.6 ± 0.1 vs 1.3 ± 0.1 ml/min/g), and increased RVR and P in ovx (23.9 ± 2.9 vs 44.8 ± 6.2 and 0.3 ± 0.01 vs 6.3 ± 1.4g/ml). These results suggest that the beneficial effects of NFkB inhibition in the kidney of aged DOCA rats are mediated by ovarian sex hormones and when ovaries are removed, the renal effects of NFkB inhibition result detrimental rather than beneficial. This work was supported by NIH AG029250‐01 award

An Uncommon Cleft Subtype of Unilateral Cleft Lip and Palate

The finding that the vomer plays a crucial role in maxillary growth suggests that the bilateral cleft configuration of unilateral cleft lip and palate (UCLP), in which the vomer is detached from the non-cleft-side secondary hard palate, negatively influences palatal development, and this hypothesis was tested. Sixty persons with complete UCLP, including those with the vomer detached from (n = 30, b-UCLP) and attached to (n = 30, u-UCLP) the secondary hard palate, were analyzed morphologically, with the use of cast models taken at 10 days, 3 mos, and 12 mos of age. The anterio-posterior palatal length at 12 mos of age in those with b-UCLP was significantly shorter than that in those with u-UCLP, by 8.7% (p < 0.05). In addition, palatal width development in the first year in those with b-UCLP was also significantly retarded. These results suggest that the uncommon bilateral cleft subtype in UCLP should be included in the cleft classification.

Long-Term Survival in Werdnig–Hoffmann Disease

To report long-term survival of spinal muscular atrophy type 1 (SMA 1) and consequences on speech and ventilator dependence as a function of mode of ventilator use. A retrospective chart review of 106 consecutively referred SMA 1 patients, the 92 most severe of which were considered in three groups: untreated (group 1), tracheostomy managed (group 2), and noninvasively managed (group 3). The untreated patients died at 9.6 +/- 4.0 mos of age. The mean age of the 22 patients referred with tracheostomy tubes (group 2) was 70.5 +/- 43.3 mos (range 2-159 mos); five died at 66.2 +/- 114.2 mos (range 8-270 mos) of age. Six had comprehendible speech at the time of tracheotomy and retained some ability to vocalize afterward. None of the 21 patients who had not developed the ability to speak did so after tracheotomy. Twenty-five of the 27 total lost all autonomous breathing ability immediately, and definitively, after tracheotomy. The 47 patients who used noninvasive mechanical ventilation (NIV) (group 3) were extubated to it during episodes of acute respiratory failure. Thirty-nine of these were 65.2 +/- 45.8 mos (range 11-153 mos) of age, and eight died at 60.9 +/- 26.1 mos (range 36-111 mos) of age. There was no significant difference in longevity with or without tracheostomy, but the NIV patients had significantly fewer (P = 0.04) hospitalizations per year after age 5; 39 of the 47 could communicate verbally, and only nine were continuously dependent on NIV. NIV and tracheostomy can both prolong survival for SMA 1 patients, but the latter results in continuous ventilator dependence and speech does not develop.

Noninvasive Ventilation in Children with Spinal Muscular Atrophy Types 1 and 2

Our aim was to assess the efficacy of noninvasive ventilation (NIV) for the treatment of thoracoabdominal asynchrony during sleep in children with spinal muscular atrophy (SMA) types 1 and 2. Nine subjects underwent assessment for sleep apnea/hypopnea index (AHI), mean oxyhemoglobin saturation (SpO2), oxygen desaturation index, transcutaneous carbon dioxide tension (tcpCO2), and mean phase angle during sleep as a measure of thoracoabdominal coordination. A second sleep study was performed with use of NIV. The nine patients (7 mos of age, range 2-33) had a baseline AHI of 2.1 events per hour (range 0.5-55.8), oxygen desaturation index of 3.7 events per hour (range 1.6-46.1), mean tcpCO2 of 46 mm Hg (range 37-60), and phase angle of 127 degrees (range 72.7-151.7). Comparing baseline and NIV sleep studies, we found significant improvement in oxygen desaturation index (P < 0.010), mean tcpCO2 (P < 0.001), and phase angle (P < 0.001). For five patients, phase-angle improvement became significant when using high-span bilevel positive airway pressure (PAP). NIV improved sleep breathing parameters and thoracoabdominal coordination during sleep in SMA types 1 and 2. Phase-angle improvement correlated with bilevel PAP pressures. Phase angle may be useful for the evaluation and monitoring of therapeutic interventions such as NIV.

In a statewide sample of WIC participants, Hispanic mothers are more likely to follow AAP infant feeding recommendations than African American or White mothers

Objective To examine how maternal infant feeding practices vary by ethnicity in a low-income statewide sample. Methods Bilingual interviewers conducted a survey on 795 mothers of infants under 13 mos who received WIC in 2004–2005. Results Rates of breastfeeding initiation and duration varied by ethnicity. Hispanic mothers (87%) were more likely to initiate breastfeeding than African American (62%)or White (58%) mothers, OR = 7.5, CI (4.0–14.1), p < .01. Hispanic mothers (4.8 mos) breastfed longer than either African American (3.8 mos) or White mothers (3.8 mos), F = 6.2, p < .01. As compared to African American and White mothers, Hispanic mothers were more likely (χ2 = 81.9, p < .01) to stop breastfeeding based on perceptions of decreased milk supply and infant hunger than concerns regarding breastfeeding pain and the need to return to work. Hispanic mothers (16%) were less likely to introduce solids before 4 mos of age than African American (42%) or White (39.5%) mothers, OR = .029, CI (.16–.53), p < .01. Hispanic mothers (30%) were less likely to add cereal to the bottle than African American (56%) and White (35%) mothers, OR = .56, CI (.35–.89), p = .016. Conclusion Hispanic mothers were more likely to follow AAP infant feeding recommendations. Further research is needed to examine the impact of these ethnic differences on feeding practices on infant nutrition and growth.

Heparin-induced thrombocytopenia in the pediatric intensive care unit population

To report the occurrence of heparin-induced thrombocytopenia (HIT), discuss its pathophysiology, and outline an approach to management in the pediatric intensive care unit (ICU) patient. Retrospective case reports. Pediatric ICU in a tertiary-care center. Two pediatric ICU patients (2 and 6 mos of age) who developed HIT in the pediatric ICU. One was receiving heparin as a flush solution through a central line and the other had full heparinization during cardiopulmonary bypass. Both had received heparin during their neonatal course and developed thrombocytopenia; however, HIT was not considered as a possible diagnosis. HIT was diagnosed using a heparin-induced platelet aggregation study. The thrombocytopenia resolved with the cessation of heparin administration. One of the patients developed a deep vein thrombosis around a femoral venous catheter. Although well described in the adult literature, there have been a limited number of reports of HIT in pediatric-aged patients. Given its potential for morbidity, HIT should be considered in the differential diagnosis of thrombocytopenia in the pediatric ICU patient.

Kawasaki Disease: Do We Need a New Case Definition?

Misdiagnosis or missed diagnosis of Kawasaki disease (KD) is a problem in the United States (U.S.). To learn about current practice in diagnosing KD, we conducted a questionnaire survey of general pediatricians in San Diego County and U.S. members of the Pediatric Infectious Disease Society. Responses were obtained from 132/227 (58.1%) generalists and 345/651 (53.0%) subspecialists. Half of the general pediatricians and 90% of the pediatric subspecialists reported having made the diagnosis of KD in febrile patients (pts) who did not fulfill 4/5 clinical criteria. When asked about clinical criteria that trigger consideration of KD, generalists and subspecialists listed fever, rash, and conjunctival injection as the top three clinical signs. Cervical lymphadenopathy was considered an important criterion by the generalists (69/131, 52.7%) but not by the subspecialists (34/334, 10.2%). Despite the well-documented occurrence of KD throughout the pediatric age group, 71/124 (57.3%) generalists and 86/325 (26.5%) subspecialists did not consider the diagnosis in pts <6 mos of age. Similarly, 64/124 (51.6%) generalists and 81/324 (25.0%) did not consider the diagnosis of KD in pts >8 yrs. Laboratory studies reported to be most helpful in establishing the diagnosis of KD were (generalists;subspecialists): erythrocyte sedimentation rate (68.2%;74.2%), complete blood count (58.1%;40.0%), platelet count (51.9%;32.1%), urinalysis (46.5%;41.2%), and echocardiogram (45.0%;52.1%). Education about KD in the U.S. must emphasize that this disease can occur across the entire pediatric age range. Physicians have found the case definition to be overly specific and inadequately sensitive in establishing the diagnosis of KD. Formulation of a new case definition for improved sensitivity in early detection of KD cases may be warranted.

A note on prespeech and early speech coarticulation

Development of consonant + vowel (CV) coarticulation was examined acoustically in two normally developing children. Data of the vocalizations from each child at 11 mos and 20 mos of age were collected. These vocalizations corresponded to prespeech and early speech periods of linguistic development, respectively. A specific CV form, common in each child's prespeech and early speech vocalizations, was selected for analysis. Coarticulation was evaluated by determining the slope of formant 1 (Fl) and formant 2 (F2) transitions following consonant release. The formant transition slopes were found to be “shallower” at 20 mos of age compared to the 11 mos period with the largest developmental change occurring for F1 transitions. Discussion focuses on the intrasyllabic coarticulatory effects characterizing prespeech and early speech development.

EARLY INTRODUCTION OF CEREAL FEEDING INCREASES ADIPOSITY OF INFANTS.† 695

The AAP recommends introducing cereal (C) into infant diet at 4-6 months(mos) of age. In practice, parents often begin C before 4 mos. Shifting a balanced diet to a carbohydrate-enriched diet may promote fat storage. We hypothesized that infants fed formula+cereal from 3 mos become heavier and have increased fat mass vs. controls fed formula alone.Methods: 12 male term formula fed infants were randomized to receive C beginning at 3 (n=6) or 5 (n=6) mos of age. Weight (wt, kg) and length (cm) were measured at birth, 3, 4, & 5 mos of age.%Fat was assessed by total body electrical conductance (TOBEC) at 3, 4 & 5 mos.Results:(mean ± SEM) Birth weight, GA and race did not differ by group. Both wt (p=0.002) and%fat (p=0.006) were significantly higher in the cereal group by repeated measures regression analysis (BMDP 5V).Conclusion: Early introduction of cereal to infant diet resulted in increased weight attributable to increased fat mass. Speculation: Increased adiposity in infants fed cereal early is due to replacement of protein rich formula with carbohydrate. This may be relevant to the development of obesity later in life. (Funded by NIDDK #DK46204)Table

EARLY AGE OF WALKING, CALCIUM INTAKE DURING INFANCY AND BONE MINERALIZATION AT 3-5.5 YEARS OF AGE. † 714

We have reported that bone mineralization at 1 y of age correlates with the age infants started walking, weight, height and calcium intake during infancy. It is unknown if this relationship extends to a later age. We hypothesized that bone mineral content (BMC) and density (BMD) in 3-5.5 y old children are affected by calcium intake at 6-12 mos of age. We evaluated total body BMC and BMD at 3-5.5 y of age in 41 healthy children previously fed one of 3 infant formulas containing different calcium contents (A=450, B=510, C=912 mg/L calcium) at 6-12 mos of age. BMC and BMD at 3-5.5 y of age were similar among the 3 study groups despite differences in calcium intake at 6-12 mos of age. BMC for A groups were (mean-+ SFM) 29.6 +- 0.7, 29.3 +- 0.6, and 29.6 +- 0.8 g/kg body weight, respectively. There were no significant correlations between BMC or BMD and previous calcium intake. BMC and BMD were positively correlated(p<0.001) with age, weight and height at bone evaluation, and negatively correlated (p<0.05) with the age subjects started walking. Thus, BMC and BMD of 3-3.5 y old children are influenced by the age infants started walking, and age, weight, and height at bone evaluation but not calcium intake levels at 6-12 mos of age. Supported by Ross Products Division, Abbott Laboratories.

FOLLOW-UP PULMONARY FUNCTION IN INFANTS AFTER INHALED NITRIC OXIDE TREATMENT OF PERSISTENT PULMONARY HYPERTENSION. 2294

Although inhaled nitric oxide (iNO) is used in the treatment of persistent pulmonary hypertension of the newborn (PPHN), little is known of its potential long term toxic effects. By decreasing intrapulmonary and extrapulmonary shunt iNO may decrease lung injury due to barotrauma and oxygen toxicity. Despite these benefits, there may be a potential risk of additional lung injury with NO therapy secondary to NO and the formation of NO related by-products(NO2, ONOO-). In this study we sought to determine if there were any differences in lung function of infants with PPHN treated with iNO compared to healthy control infants. Five infants (ages 6 to 9 mos) with a history of PPHN treated with iNO were compared with five normal control infants (5.5 to 6 mos of age). None of the infants were on home oxygen. Pulmonary function tests were performed using the Sensormedics 2600 Infant PFT system. Oxygen saturations were not different between study groups. Thus, NO treated infants at follow-up have normal lung mechanics, but mild elevation of FRC in comparison with normal controls. We conclude that these infants have normal lung mechanics but may have a tendency for gas trapping.Table

The Role of Dispersal in Structuring the Chitwan Tiger Population

AbstractDispersal in tigers was studied in Royal Chitwan National Park, Nepal. Thirty six adult and young were studied to monitor movements and social interactions relative to dispersal. Fourteen subadults were followed from before their dispersal until they died or established post-dispersal territories. Subadult tigers became semi-independent of their mother when her next litter was born. They usually remained within her natal area until the subsequent litter began to move with her at about 2 mos of age. Animals dispersed between 19 and 28 mos. Males dispersed farther than females and settled in poorer habitat. Three of 4 females settled adjacent to their mothers; in two cases the mother shifted her territory allowing the daughter to take over a large portion of the mother's former territory. Wounds on young prior to dispersal indicated that aggression prompted dispersal. Fjghts were observed between dispersers and residents. After fights, dispersers always left the resident's area. All 4 dispersing females established breeding territories. Females settled next to their mothers tending to reduce the genetic variance of a male's offspring. Eight of 10 males became localized in temporary, post-dispersal territories; 4 of the 8 survived. Two males died of poisoning and 2 from intrasexual aggression. Surviving males either expanded temporary territories or shifted to new areas to establish breeding territories. The Chitwan tigers are an isolated remnant of a population once continuous across the lowlands of Nepal. Effective population size was estimated to be &lt;30 animals. Tigers did not disperse across cultivated areas but did travel through degraded forest habitat. No animal dispersed outside the Chitwan region and there appear to be effective barriers separating Chitwan from the two nearest populations 150 and 250 kms distant. The Chitwan population is probably one of the largest tiger populations remaining in the world. Isolation and small size threaten these populations with stochastic events that may lead to further reduction in population size.

The Decidual Cell Response in Aging C57BL/6J Mice is Potentiated by Long-term Ovariectomy and Chronic Food Restriction

The effects of long-term ovariectomy (LOVX) and chronic food restriction on the decidual cell response were examined in aging mice. At 2 mos of age, mice were either ovariectomized, started on a regimen of food restriction (70% of ad lib intake), or left untreated. At 10 mos, the decidual cell response (DCR) was induced in all groups and measured by uterine weight gain, alkaline phosphatase activity, and DNA content. The DCR was also examined in young (4.5 mos) mice. LOVX and, to a lesser extent, food restriction (FR) potentiated the DCR, as indicated by 20-75% greater alkaline phosphatase activity and uterine weight relative to age-matched controls. In contrast to previous reports, however, there was no age-related reduction of the DCR. These results show that both LOVX and FR can enhance uterine function in middle-aged mice and indicate that, under some experimental conditions, there is no age-related impairment in the DCR.

733 REDUCTION OF SERUM IONIZED CALCIUM (iC) AND ELEVATION OF SERUM PHOSPHORUS IN COW MILK FORMULA FED INFANTS COMPARED TO BREAST FED INFANTS IN THE FIRST SIX MONTHS OF LIFE

Cow milk may result in neonatal hypocalcemic tetany in term infants at one wk of age. Current US cow milk formulas are modified to have lower P contents and should minimize adverse effects on Ca metabolism. However these formulas still contain more P (33-40 mg/dl) vs breast milk (13 mg/dl) and there are no studies on iCa and P in formula vs breast fed infants in the first 6 mos of age. We hypothesized that the higher intake of P in formula vs breast fed infants results in greater serum P but lower iCa. In a 24 factorial design cross-sectional study controlled for sex, race, season and diet, we evaluated serum Ca, iCa and P by diet (formula vs breast) in 119 normal, term infants <6 mo of age. No differences in serum Ca, iCa or P by season, race or sex were found. Total serum Ca did not differ between breast- and bottle-fed with means (±sem) of 9.75 (0.09) and 9.73 (0.06) mg/dl. However, iCa (Radiometer electrode, N adults 4.8-5.2 mg/dl, CV 1.1-2.6%) was lower in bottle- (5.27±0.02 mg/dl) vs breast-fed infants (5.38±0.03) (p=0.005). Serum P was higher (6.98±0.08) for bottle- vs 6.44 (±0.10) in breast-fed (p<0.001). There were no correlations of C-terminal or intact PTH by radioimmunoassay with iCa or P. Thus, serum iCa is lower and P is higher in formula- vs breast-fed infants. We speculate that the lower Ca:P ratio in cow milk formula (1.3:1) compared to that of breast milk (2:1) may be responsible for these observed differences.

1265 SEASONAL CHANGES IN SERUM VITAMIN D BINDING PROTEIN IN INFANCY: RELATION TO SUN EXPOSURE

Vitamin D binding protein (DBP) is the major carrier for vitamin D and its metabolites in serum. Its physiologic regulation is unclear; DBP increases in pregnancy and decreases in cirrhosis; no seasonal variation has been reported in adults. We hypothesized that serum DBP in infants would not vary by season. 41 exclusively breast-fed, non-D supplemented infants <6 mos of age were studied. DBP was measured by radial immunodiffusion: adult range, 276-505 ng/ml, cv 2.9% intra- and 7.6% inter-assay. 25-Hydroxyvitamin D (25-OHD) as an indicator of vitamin D status was measured by protein binding assay. Winter DBP exceeded summer: 377±12 vs 302±7 ug/ml (x+sem, p=.003). Serum 25-OHD exhibited an opposite pattern: 14±2 vs 26±2 ng/ml (p<.001). Maternal DBP did not differ by season: 374 and 373 ug/ml for winter and summer. An ultraviolet exposure score, previously verified, was used to document time and body surface exposed to sun. DBP was inversely related to sun exposure (r= -.41, p=.01). Infant DBP was significantly & negatively correlated with 25-OHD (r=-0.38, p=0.02). Two subsequent independent studies, 1 cross-sectional & 1 longitudinal, yielded similar results: infant DBP being significantly higher in winter vs summer. Thus vitamin D binding protein in exclusively breast fed infants is elevated in winter (vs summer), in low sun exposure, and in low vitamin D status as reflected by low serum 25-OHD; we speculate that serum vitamin D binding protein fluctuations are a response to varying vitamin D needs: increased DBP occurs in low vitamin D status to maximize uptake of vitamin D from skin.