Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. (17/31363)

BACKGROUND: The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR. METHODS: We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter. RESULTS: Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control. CONCLUSIONS: Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.  (+info)

Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Pediatric Pharmacology Research Unit Network. (18/31363)

Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 +/- 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Ycalc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means +/- standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (Cmax) was 1,272.5 +/- 622.1 ng/ml. The time to Cmax was 4.1 +/- 1.5 h, and the lag time was 0.75 +/- 0.56 h. The apparent absorption rate constant was 0.75 +/- 0.48 1/h, and the elimination rate constant was 0.16 +/- 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 +/- 3,411.82 ng.h/ml. The apparent total plasma clearance was 0.81 +/- 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 +/- 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 +/- 148.2 ng/ml) and 24 h (137.9 +/- 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that from in vitro studies reported to inhibit > 90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections.  (+info)

Aging-specific expression of Drosophila hsp22. (19/31363)

hsp22 is among the least abundantly expressed Drosophila heat shock (hs) genes during both development and heat stress. In contrast, hsp22 was found to be the most abundantly expressed hs gene during Drosophila aging. During aging, hsp22 RNA was induced 60-fold in the head, with somewhat lower level induction in abdomen and thorax. Induction of the other hs gene RNAs was 150-fold, with particularly abundant expression in eye tissue. Aging-specific induction of hsp22 was reproduced by hsp22:lacZ fusion reporter constructs in transgenic flies. Analysis of specific promoter mutations in transgenic flies indicated that functional heat shock response elements are required for hsp22 induction during aging. Finally, comparison of hsp22 RNA and protein expression patterns suggests that aging-specific expression of hsp22 is regulated at both the transcriptional and the posttranscriptional levels. Aging-specific induction of hsp22 is discussed with regard to current evolutionary theories of aging.  (+info)

Characterization of CD4+ CD8alphaalpha+ and CD4-CD8alphaalpha+ intestinal intraepithelial lymphocytes in rats. (20/31363)

Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ T cells expressing TCR alphabeta. In the present study, we compared characteristics between CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old Lewis rats. Most of the CD4+CD8alphaalpha+ i-IEL were of the CD44(hlgh) phenotype, while CD4-CD8alphabeta+ i-IEL were CD44(low). Vbeta usage in the CD4-CD8alphaalpha+ i-IEL was much diversified, while CD4+CD8alphaalpha+ i-IEL showed a skewed Vbeta repertoire. The CD4+CD8alphaalpha+ i-IEL but not the CD4-CD8alphaalpha+ i-IEL proliferated in response to syngeneic spleen cells, which was partially inhibited by addition of anti-MHC class I mAb. The CD4+CD8alphaalpha+ i-IEL produced IFN-gamma and IL-2 but no IL-4 or transforming growth factor (TGF)-beta in response to syngeneic spleen cells, while CD4-CD8alphaalpha+ i-IEL produced abundant levels of TGF-beta but no IL-2, IFN-gamma or IL-4. CD4+CD8alphaalpha+ i-IEL proliferated in response to exogenous IL-2 but not to IL-15, while CD4-CD8alphaalpha+ i-IEL could respond to IL-15 as well as IL-2. These results suggest that a significant fraction of CD4+CD8alphaalpha+ i-IEL belongs to Th1-type T cells capable of responding to self-MHC class I, while CD4-CD8alphaalpha+ i-IEL are a unique population with a diversified Vbeta repertoire that respond to IL-15 in rats.  (+info)

Differences in heart rate variability between young and elderly normal men during graded head up tilt. (21/31363)

An autoregressive spectral analysis of heart rate variability (HRV) was used to analyze the differences in autonomic functions during graded head up tilt (HUT) between young and elderly men. After recording at the 0 degree position, the table was rotated to an upright position. The incline of the table was increased progressively to 15 degrees, 30 degrees and 60 degrees. The data obtained from seven young subjects (mean age of 20.0 years) and nine elderly subjects (mean age of 63.3 years) were analyzed. The high frequency components expressed by normalized units (HFnu) were used as the parasympathetic indicators, and HFnu decreased with tilt angle in both age groups. These results suggested that parasympathetic withdrawal have an important role in adaptation to an upright posture in both age groups. However, mean HF amplitude at the 0 degree position in elderly men was not significantly different from that of young men at 60 degrees tilt. A significant interaction effect (age group x tilt angle) was found for mean HF amplitude. The increase of the low frequency components expressed by normalized units (LFnu) and the LF-to-HF ratio in elderly subjects from 0 degree to 15 degrees seemed to be larger than that in young subjects. Sympathetic activities may be sensitive to lower levels of orthostatic stress in the elderly, and the elderly workers are easily affected by a change in workload. Therefore, keeping the workload lower and constant may be recommended to avoid excessive sympathetic activation among the elderly.  (+info)

The effect of age and teat order on alpha1-acid glycoprotein, neutrophil-to-lymphocyte ratio, cortisol, and average daily gain in commercial growing pigs. (22/31363)

The objectives of the study were to evaluate age and teat order on a performance trait, average daily gain, and on physiological stress indicators, alpha1-acid glycoprotein (AGP), neutrophil-to-lymphocyte ratio (N:L), and cortisol in commercial growing pigs from weaning to market age. Pigs (n = 129) from five commercial California farms were weighed and blood-sampled at 28-d intervals from 28 to 168 d of age. Laboratory assays were performed from blood samples to quantify cortisol, AGP, and N:L. Age and facility effects (P<.001), but not teat order effects (P>.05), were found for all three physiological traits and ADG. Pigs that routinely suckled from teats 1, 4, or 6 (numbered from anterior to posterior on the upper teat bank) had similar (P>.05) ADG and BW throughout the production cycle. No correlation (P> .05) was found between cortisol, AGP, and N:L. The use of these physiological and production traits as stress and health indices of growing pigs in commercial facilities has limitations in comparing data between facilities or different ages of pigs.  (+info)

Diurnal variation and age differences in the biochemical markers of bone turnover in horses. (23/31363)

Biochemical markers of bone turnover provide sensitive, rapid, and noninvasive monitoring of bone resorption and formation. Serum concentrations of osteocalcin (OC) reflect rates of bone formation, and urinary concentrations of the pyridinium crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpd) are specific and sensitive markers of bone resorption. These markers are age-dependent and are used to detect and monitor changes in the rates of bone turnover in a variety of orthopedic diseases in humans and may prove to have similar application in horses. This study examined age differences and diurnal variation in OC, Pyd, and Dpd in eight adult geldings and seven weanling colts. Blood and urine were collected at regular intervals over 24 h. Serum OC and cortisol, and urinary Pyd and Dpd were analyzed. Mean 24-h concentrations of cortisol and all three markers were higher (P<.003) in weanlings than adults. Significant 24-h variation was observed in adult gelding OC, Pyd, and Dpd concentrations (P< .02). Adult OC concentrations were highest between 2400 and 0900; Pyd and Dpd peaked between 0200 and 0800. Similar patterns of bone turnover were observed in weanling values, but they were not significant (P>.17) owing to greater variability between individuals. Cortisol secretion varied (P<.001) over 24 h in both adults and weanlings and, thus, did not seem to be responsible for greater variability in markers of bone turnover between weanlings. These data demonstrate that diurnal rhythms exist for serum OC and urinary Pyd and Dpd in adult horses, as reported in humans, and that sample timing is an important consideration in future equine studies using these markers.  (+info)

Utilization of bioelectrical impedance to predict carcass composition of Holstein steers at 3, 6, 9, and 12 months of age. (24/31363)

The objective of this experiment was to study the usefulness of bioelectrical impedance analysis (BIA) in determining soft tissue composition (STC) and carcass fat-free mass (CFFM) of Holstein steers at different ages. Growth data and prediction of STC and CFFM were determined for four groups of Holstein steers: 12 of 3 mo, 12 of 6 mo, 15 of 9 mo, and 16 of 12 mo of age. Average weight for animals at 3, 6, 9, and 12 mo were 96.6, 204.7, 354.1, and 465.9 kg, respectively. Average fat content of carcass soft tissue at 3, 6, 9, and 12 mo were 2.6, 9.8, 18.2, and 24.6%, respectively. Average protein content of the carcass soft tissue was 20.7% at 3 mo, 20% at 6 mo, 18.30% at 9 mo, and 16.9% at 12 mo of age. Feed and water were withheld for 20 h before the BIA was applied. Steers were sedated and forced to recumbency in a lateral position on their right sides over a nonconductive surface. Two electrodes were placed on each limb of the right side (metatarsal and metacarpal regions on back and front foot, respectively). Resistance (Rs) and reactance (Xc) were obtained by attaching four terminals to the electrodes. Impedance and other predictors such as Vol1 (L/Rs), Vol2 (L2/(RS2+Xc2).5, Vol3 (geometrical animal volume), L (2 x height + body length), and L2 were calculated from Rs and Xc, and body measurements and were used to generate prediction equations for CFFM and carcass soft tissue composition. Carcass fat-free mass was predicted accurately for all age groups and the pooled data (r2 = .99 at 3 mo, .99 at 6 mo, .97 at 9 mo, .77 at 12 mo, and .98 for the pooled data). Correlation coefficients between impedance readings and CFFM and carcass composition were calculated. Carcass CFFM and kilograms of H2O for the pooled data (across age groups) were both correlated highly to Vol1 (.97), Vol2 (.95), L (.97), and L2 (.97).  (+info)