Does Vibration Warm-up Enhance Kinetic and Temporal Sprint Parameters?

The aim of this study was to investigate the efficacy of vibration warm-up to enhance sprint performance. 12 males involved in representative team sports performed 4 warm-up conditions in a randomised order performed at least 24 h apart; VbX warm-up (VbX-WU); Neural activation warm-up (Neu-WU); Dynamic warm-up (Dyn-WU) and Control (No VbX). Participants completed 5 m sprint at 30 s, 2:30 min and 5 min post warm-up where sprint time, kinetics, and temporal components were recorded. There was no significant (p>0.05) main effect or interaction effect between the split sprint times of 1 m, 2.5 m, and 5 m. There was a condition effect where vertical mean force was significantly higher (p<0.05) in Dyn-WU and Control compared to Neu-WU. No other significant (p>0.05) main and interaction effects in sprint kinetic and temporal parameters existed. Overall, all 4 warm-up conditions produced comparable results for sprint performance, and there was no detrimental effect on short-duration sprint performance using VbX-WU. Therefore, VbX could be useful for adding variety to the training warm-up or be included into the main warm-up routine as a supplementary modality.

Three-month assessment of safety and efficacy of two electric toothbrushes.

OBJECTIVE.: This randomised, examiner-blind parallel group study was designed to evaluate the safety and efficacy of a rechargeable oscillating/pulsating toothbrush (Oral-B ProfessionalCaretrade mark 7000, Oral-B Laboratories; PC 7000) and a battery-operated toothbrush (Crest(R) SpinBrushtrade mark Pro, Procter & Gamble Company; SBP) in the reduction of gingivitis, bleeding and plaque over a 3-month period. METHODS.: After 12-18 hours of no oral hygiene, subjects had oral tissue examinations, and gingival and plaque assessments to determine eligibility in the study. Subjects were stratified and randomised into treatment groups based on initial whole mouth mean plaque (Turesky modification of Quigley Hein Plaque Index) and gingivitis (Löe & Silness Gingival Index) scores and gender. Subjects were instructed to brush twice daily with their assigned toothpaste and toothbrush. Clinical parameters were assessed at baseline, and after 1 and 3 months of use. Within treatment comparisons from baseline were analysed using t-test; between treatment comparisons were analysed using ANOVA. RESULTS.: Data were obtained from 92 subjects (PC 7000 n=45; SBP n=47). No significant differences were found in baseline plaque, gingivitis and bleeding between groups. Both treatment groups had significant reductions from baseline in plaque, gingivitis and bleeding scores. PC 7000 demonstrated significantly greater reductions compared to SBP in whole mouth plaque at 1 month: 0.39+/-0.43 vs. 0.16+/-0.42 and 3 months: 0.32+/-0.48 vs. 0.04+/-0.41. PC 7000 also demonstrated significant reductions compared to SBP in gingivitis at 3 months for whole mouth: 0.14+/-0.09 vs. 0.10+/-0.10 and approximal areas: 0.11+/-0.08 vs. 0.08+/-0.09. There were no significant differences between toothbrushes in bleeding at either time point. Safety examinations revealed no apparent difference in soft and hard tissue abnormalities between groups. CONCLUSION.: The PC 7000 toothbrush demonstrated significantly greater reductions in plaque and gingivitis compared to the SPB over a 3-month period.

Three-month assessment of safety and efficacy of two electric toothbrushes.

OBJECTIVE: This randomised, examiner-blind parallel group study was designed to evaluate the safety and efficacy of a rechargeable oscillating/pulsating toothbrush (Oral-B ProfessionalCare 7000, Oral-B Laboratories; PC 7000) and a battery-operated toothbrush (Crest SpinBrush Pro, Procter & Gamble Company; SBP) in the reduction of gingivitis, bleeding and plaque over a 3-month period. METHODS: After 12-18 hours of no oral hygiene, subjects had oral tissue examinations, and gingival and plaque assessments to determine eligibility in the study. Subjects were stratified and randomised into treatment groups based on initial whole mouth mean plaque (Turesky modification of Quigley Hein Plaque Index) and gingivitis (Löe & Silness Gingival Index) scores and gender. Subjects were instructed to brush twice daily with their assigned toothpaste and toothbrush. Clinical parameters were assessed at baseline, and after 1 and 3 months of use. Within treatment comparisons from baseline were analysed using t-test; between treatment comparisons were analysed using ANOVA. RESULTS: Data were obtained from 92 subjects (PC 7000 n=45; SBP n=47). No significant differences were found in baseline plaque, gingivitis and bleeding between groups. Both treatment groups had significant reductions from baseline in plaque, gingivitis and bleeding scores. PC 7000 demonstrated significantly greater reductions compared to SBP in whole mouth plaque at 1 month: 0.39 +/- 0.43 vs. 0.16 +/- 0.42 and 3 months: 0.32 +/- 0.48 vs. 0.04 +/- 0.41. PC 7000 also demonstrated significant reductions compared to SBP in gingivitis at 3 months for whole mouth: 0.14 +/- 0.09 vs. 0.10 +/- 0.10 and approximal areas: 0.11 +/- 0.08 vs. 0.08 +/- 0.09. There were no significant differences between toothbrushes in bleeding at either time point: Safety examinations revealed no apparent difference in soft and hard tissue abnormalities between groups. CONCLUSION: The PC 7000 toothbrush demonstrated significantly greater reductions in plaque and gingivitis compared to the SPB over a 3-month period.

Anticalculus efficacy of an antiseptic mouthrinse containing zinc chloride.

BACKGROUND: The authors undertook a controlled clinical study to determine the efficacy of a tartar-control antiseptic mouthrinse in inhibiting the development of supragingival dental calculus. METHODS: After undergoing a dental prophylaxis, 334 subjects with a moderate rate of calculus formation were stratified and randomly assigned to one of three groups: positive control (using a tartar-control toothpaste and an antiseptic rinse), negative control (using a regular toothpaste and an antiseptic mouthrinse) or experimental (using a regular dentifrice and a tartar-control mouthrinse). Subjects brushed and rinsed twice daily, unsupervised, for four months. The researchers assessed subjects' calculus levels using the Volpe-Manhold Index, or VMI, after 16 weeks. RESULTS: Using analysis of covariance, the authors found that both the experimental group (which used a tartar-control rinse containing zinc chloride) and the positive control group (which used a tartar-control dentifrice containing pyrophosphate) demonstrated statistically significantly lower VMI scores (P = .001) than the negative control group (which used a regular dentifrice and an antiseptic rinse). Both anticalculus agents provided a clinically relevant 21 percent reduction in calculus formation. CONCLUSION: An antiseptic mouthrinse containing 0.09 percent zinc chloride as the anticalculus agent provides a clinically relevant reduction in calculus formation in people with a moderate rate of such formation. CLINICAL IMPLICATIONS: A tartar-control mouthrinse with zinc chloride as the tartar-control ingredient is clinically effective in reducing the formation of calculus.

A single-use and 3-month clinical investigation of the comparative efficacy of a battery-operated power toothbrush and a manual toothbrush.

PURPOSE: To compare the safety and efficacy of a manual toothbrush and a battery-operated power toothbrush in two separate studies, one utilizing a single-use design and the other a 3-month parallel-group design. MATERIALS AND METHODS: The toothbrushes compared in the two studies were the Oral-B CrossAction manual toothbrush and the Colgate Actibrush battery-operated power toothbrush. The single-use study, which used a single-blind, cross-over design, involved 71 healthy subjects, who were instructed to abstain from oral hygiene for 23-25 hours prior to brushing with each of the two toothbrushes. Plaque was measured using the Proximal Marginal Index (PMI) pre- and post-brushing. The 3-month parallel-group study involved a total of 113 subjects who had plaque (PMI), gingivitis and bleeding (Loe and Silness) scored at baseline and after 1 and 3 months of product use. RESULTS: In both studies, the two toothbrushes were found to be safe. In the single-use study, significantly greater amounts of plaque were removed by the CrossAction manual toothbrush than by the Actibrush for the whole mouth as well as for marginal and approximal sites (P < 0.001). In the 3-month study, significantly greater plaque reduction was achieved with the CrossAction brush, the advantage being significant at 1 month for all sites except lingual sites (P < 0.05). At 3 months, there were consistent numerical advantages in favor of the CrossAction at all sites except lingual sites. Reductions in gingivitis were found to be similar with both toothbrushes.

A comparative single-use clinical study of the efficacy of two manual toothbrushes with angled bristles.

PURPOSE: To compare the safety and plaque removal efficacy of two angled-bristled toothbrushes. MATERIALS AND METHODS: The brushes were compared using a single-use, cross-over designed study, where healthy subjects from a normal population brushed their teeth with their assigned toothbrush for a timed 60 seconds. Pre- and post-brushing plaque levels were evaluated after disclosing, using the Proximal/Marginal Plaque Index. At the first visit, 100 subjects with a plaque index of > or = 2.20 after 23-25 hours of no oral hygiene were enrolled in the study. At the end of the study, data from 91 subjects were suitable for analysis. The two treatment sequence groups, X-Aktiv/CrossAction and CrossAction/X-Aktiv, were balanced for age and gender and, at each visit, pre-brushing plaque scores did not differ significantly between the two groups. Data from the two visits were pooled, after which plaque removal efficacies were compared. RESULTS: Both toothbrushes were found to be safe and both significantly reduced plaque levels (P< or = 0.0001), but the CrossAction was significantly more effective than the X-Aktiv for whole mouth and marginal sites, as well as the difficult-to-access approximal areas (P< or = 0.0008). For the whole mouth, the CrossAction was 11.8% more effective; for marginal sites the difference was 12.6%, and for approximal sites the difference was 11.4%. It is concluded that the Oral-B CrossAction toothbrush is significantly more effective with respect to plaque removal than the Dr. Best X-Aktiv.

A comparative clinical investigation of a novel toothbrush designed to enhance plaque removal efficacy.

PURPOSE: To investigate the safety and efficacy of a new toothbrush with a novel brush head design (Oral-B CrossAction) in comparison with seven leading manual brushes. MATERIALS AND METHODS: Seven independent clinical studies, each involving approximately 100 healthy subjects from a general population, were carried out using a crossover design. In each study, the Oral-B CrossAction toothbrush was compared with an alternative brush for plaque removal efficacy. Plaque was evaluated before and after brushing for 60 s using the Proximal/Marginal Plaque Index. Subjects were randomly assigned to the two brushes in each study and after brushing at visit 1 they returned after a further 2 weeks to repeat the procedure with the second brush. RESULTS: All toothbrushes in the seven studies significantly reduced levels of plaque from their pre-brushing values and were found to be safe with no evidence of oral soft tissue trauma. In each of the studies, the CrossAction was found to be significantly (P < 0.05) more effective than the comparison brush for whole mouth plaque scores, as well as for plaque scores at the gingival margin and proximal surfaces. Advantages in favor of the CrossAction ranged from 9.8% to 23.2% for whole mouth plaque, from 5.3% to 20.6% for the gingival margin and from 12.8% to 24.5% for proximal surfaces. It was concluded that the novel brush head design of the CrossAction toothbrush provides enhanced plaque removal, especially from proximal surfaces, and that this toothbrush is significantly more effective than all seven toothbrushes tested.

Peripheral neuropathy in transgenic diabetic mice: restoration of C-fiber function with human recombinant nerve growth factor.

Mice (Ins.Dd1) with hypoinsulinemic diabetes were created by increased expression of syngeneic major histocompatibility complex (MHC) class I protein in pancreatic beta-cells. The diabetic state was characterized in these mice by high glucose concentrations and islet pathology. To determine whether a neuropathy would develop, motor and sensory conduction velocities (CV) were determined in the sciatic nerves of 2-, 4-, and 7-month-old control and diabetic littermate male mice. Recording bipolar electrodes were placed in the plantar muscles of the hind foot of anesthetized (ketamine/xylazine) mice. Bipolar stimulating electrodes were positioned near the sciatic nerve at the sciatic notch or near the tibial nerve at the ankle. Motor CV from alpha-motor fibers and sensory CV from proprioceptive Aalpha nerves were measured and expressed as meters per second (m/s). Group data are reported as mean +/- SE and compared by analysis of variance. The CVs from nondiabetic mice (controls) were not different across the three ages and averaged 41.3 +/- 1.7 m/s for motor and 38.7 +/- 1.7 m/s for sensory. The motor CVs from diabetic mice at 2 and 4 months were similar to controls. Sensory CVs were unchanged at 2 months but were lower at 4 months (18.9 +/- 2.4 m/s). Both sensory (23.9 +/- 2.1 m/s) and motor (18.9 +/- 1.8 m/s) CVs were significantly reduced at 7 months, which is indicative of a polyneuropathy. NGF has well-known trophic effects on sympathetic and small sensory neurons. To determine whether NGF could influence this neuropathy, 6-month-old control and diabetic mice were divided into the following groups: 1) control + vehicle, 2) diabetic + vehicle, and 3) diabetic + NGF (1 mg/kg, 3x week, s.c.). After 1 month of treatment, motor and sensory CVs were determined. In some mice, the branches of the sciatic nerve were exposed and in situ recordings from the sural nerve were performed to determine compound C-fiber CV, integral, and amplitude. Sensory CV, determined via Hoffmann's reflex (H-reflex) (A-fiber), was decreased in diabetic compared with control animals as expected (P < 0.05), and NGF did not alter this parameter. Continuing diabetes reduced the amplitude (0.9 +/- 0.2 vs. 3.2 +/- 0.7 mV x 10(-2); P < 0.05) and integral (6.9 +/- 1.9 mV/ms vs. 18.8 +/- 4.4 mV/ms; P < 0.05) of the C-fiber response versus control, suggesting fiber loss. NGF treatment normalized C-fiber amplitude (2.9 +/- 0.8 mV x 10(-2)) and integral (21.2 +/- 6.5 mV/ms) in animals with established diabetes, with no effect on blood glucose. The C-fiber CV was similar in all groups, indicating that the animals had some normally conducting small fiber sensory nerves. These studies characterized a motor and sensory polyneuropathy in transgenic diabetic mice and are the first to demonstrate directly that NGF treatment can protect or restore abnormal sensory C-fiber function.

Insulin-like growth factors (IGFs) and IGF binding proteins, serum acid-labile subunit and growth hormone binding protein in nephrotic children.

We hypothesized that the increased glomerular permeability to serum proteins in the nephrotic syndrome might lead to alterations of the somatotropic hormone axis, thereby contributing to growth failure and catabolism in the nephrotic state. The insulin-like growth factors (IGF)-I and -II and the IGF binding proteins (IGFBP)-1, -2 and -3 were analyzed in serum and urine of 21 children with the nephrotic syndrome and normal glomerular filtration rate. Mean age-related serum IGF-I levels by RIA (-0.53 +/- 0.34 SD) were slightly, but significantly (P < 0.05) decreased compared with the reference population, whereas mean age-related serum IGF-II levels (0.68 +/- 0.21 SD) were slightly, but significantly (P < 0.005) increased. The urinary excretion rate of both peptides was enhanced fivefold. By RIA, mean age-related serum IGFBP-1 (2.05 +/- 0.19 SD) and, even more pronounced, IGFBP-2 (5.97 +/- 0.65 SD) were clearly elevated despite a 12-fold and 2-fold increase of the respective urinary excretion rate. There was a tight and specific correlation between age-related serum IGFBP-2 levels and the degree of the nephrotic syndrome, as estimated by serum albumin levels (r = -0.78, P < 0.0001). Serum immunoreactive IGFBP-3 levels were also elevated (1.79 +/- 0.33 SD) in nephrotic serum, due to an increase of low-molecular weight IGFBP-3 fragments. By FPLC analysis, there was a decrease of the 150 kDa IGFBP ternary complex in nephrotic serum, which in the presence of normal concentrations of the acid-labile subunit by RIA appears to be due to a reduction of intact IGFBP-3. Serum levels of the high-affinity GH binding protein that presumably reflects GH receptor status in tissues were normal. In summary, total serum IGFs in children with the nephrotic syndrome are normal, but the binding of IGFs to IGFBPs in the circulation is altered with a shift from the 150 kDa IGFBP complex to an excess of low molecular weight IGFBPs. Because increased unsaturated high-affinity IGFBPs in nephrotic serum have the ability to inhibit IGF action on target tissues by competing with the type 1 IGF receptor for IGF binding, this alteration is likely to contribute to growth failure and tissue catabolism in the nephrotic state.

Pioneering recombinant growth hormone manufacturing: pounds produced per mile of height.

The first efforts to produce recombinant human growth hormone (GH) for clinical use were begun by scientists at Genentech, Inc., almost a generation ago, late in 1979. The very small market for GH that was predicted at the time led to this manufacturing effort being done as a demonstration project. Among the early issues was whether the Escherichia coli host cell could be routinely produced in a stable manner and be inactivated after the GH production run (as required by Federal guidelines) without the GH being permanently denatured. A 10 L E. coli process was developed, and phase I testing began in early 1981. The approval of this recombinant GH product by the FDA in 1985 paved the way for many improvements and a sustained production effort in the next decade. The more than 1990 fermentation runs have produced tons of E. coli and more than 130 pounds of GH for both clinical research and the treatment of severely short children.

Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.

Developmental differences in the IGF-I system response to severe and chronic calorie malnutrition.

Recent studies in children suggest that there are age-related differences in the insulin-like growth factor I (IGF-I) response to malnutrition. To extend this observation, immature 4-wk-old male rats were fasted for 3 days, fed ad libitum (control), or fed 60 or 40% of control calories (restricted) and compared with 8-wk-old young adults. Over the 3-wk study period, serum total IGF-I levels of the older rats were stable despite reduced insulin levels, whereas IGF-I increased 2.2-fold in the younger controls. With the 40% diet, younger and older rats changed body weight +1 and -1 body wt/day, respectively (P < 0.0001). The restricted younger animals reduced serum IGF-I IGF binding protein-3, acid-labile subunit, and growth hormone binding protein levels significantly more than the restricted older animals. Fasting decreased most of these parameters by 40%, serum insulin by approximately 80%, and body weight by 9%, regardless of age. We conclude that the suppression of the IGF-I system in response to chronic undernutrition, but not acute fasting, is greater in maturing than young adult rats.

In vitro characterization of four novel classes of growth hormone-releasing peptide.

Reexamination of the hexapeptide GH-releasing peptide (GHRP-6) structure/function has lead to the development of four novel classes of compound that stimulate GH release. Each class is represented as follows: a pentapeptide, G-7039; a tetrapeptide, G-7134; a pseudotripeptide, G-7502; and a rigid cyclic heptapeptide, G-7203. The EC50 values for these compounds, determined by GH dose-response curves using primary cultures of rat pituitary cells, were 0.18, 0.34, 10.6, and 0.43 nM, respectively. To demonstrate that these compounds were acting at the putative GHRP receptor, challenges were made using combinations that included GHRP-6 and GH-releasing hormone (GHRH). All four new classes further increased GH release in combination with GHRH, but not with GHRP-6. Homologous desensitization occurred after 45 min of exposure to the new compounds while the cells remained sensitive to GHRH. Somatostatin inhibited all of these compounds. Additionally, G-7039 elevated free calcium, as occurs with GHRP-6. All four classes elicited a robust GH release, a small increase in PRL, and no change in LH, FSH, ACTH, or TSH. We conclude that these novel compounds are potent and direct stimulators of pituitary GH release, with in vitro attributes that suggest mediation via a specific GHRP-like mechanism.

Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition.

The hierarchy of diet components (e.g., protein, carbohydrate, vitamins, and minerals) influencing growth hormone (GH), insulin-like growth factor-I (IGF-I), and their binding proteins (BP) is not well defined. Young adult rats were fed diets for 1 mo that included low protein or 60% and 40% of carbohydrate calories. We hypothesized that levels of both hormones, their dominant BPs and liver IGF-I mRNA would fall, and that part of the mechanism for decreasing serum IGF-I would be enhanced IGFBP-3 protease activity. By day 30, caloric deprivation to 40% lowered serum GH, GHBP, IGF-I and IGFBP-3, and liver IGF-I mRNA. This was the only condition resulting in body weight loss (-15%) vs 39% gain in controls. Restriction to 60% calories had no impact on BP levels, slightly lowered IGF-I (-12%) in the face of a 95% inhibition of GH levels, while allowing a modest 9% body weight gain. Protein deprivation lowered serum GH, IGF-I and IGFBP-3, and liver IGF-I mRNA, while GHBP levels were normal. The reduced total IGF-I under these dietary conditions could not be explained by an increase in IGFBP-3 protease activity, or a decrease in the association of IGF-I with IGFBP-3 and the acid labile subunit.

Relaxin increases rat heart rate by a direct action on the cardiac atrium.

Relaxin (Rlx) is best understood as a protein hormone of pregnancy that can influence pelvic and cervical connective tissue as well as uterine smooth muscle activity. Thus, it was unexpected that dense Rlx binding sites would be found in the rat cardiac atrium. To functionally characterize this finding, isolated rat atria were challenged with Rlx (0.3 to 30 ng/ml), and they responded with an increased rate (+36%) and force (+38%) of contraction Further studies in conscious normotensive and spontaneously hypertensive rats established by minipump circulating Rlx levels of about 0.5 and 5 ng/ml over 1 to 2 wks. There were significant increases in heart rate of 10-15%, with no consistent changes in blood or urine volume, water or food intake, and mean arterial pressure. We conclude that Rlx can directly stimulate rat cardiac atrial activity in vitro and cause chronotropy in vivo.

Relaxin binding in the rat heart atrium.

Relaxin is a member of the insulin family of polypeptides that is best known as a reproductive hormone. In an effort to elucidate the mechanism of action of relaxin we previously localized the specific binding sites of a 32P-labeled relaxin in the rat uterus and brain. These studies suggested that, in addition to its classical role in pregnancy, relaxin might have other physiological functions. In the present paper we describe the specific and high-affinity binding of relaxin to the cardiac atrium of both male and female rats. The relaxin binding could not be displaced by peptides belonging to the same family [insulin, insulin-like growth factor I (IGF-I)] or by peptides that were identified in the atrium or were known to have cardiovascular functions (atrial natriuretic peptide, angiotensin II). The dissociation constant for relaxin in the atrium was estimated to be 1.4 nM, which was similar to that found in the uterus (1.3 nM) and the brain (1.4 nM). In view of the close association of relaxin with reproduction, an experiment was also performed to compare the relaxin binding in the uterus and heart after gonadectomy and sex steroid treatment. It was found that the relaxin binding in the rat uterus was diminished by 53% overall following ovariectomy but was restored to 90% of normal levels when treated with estrogen (but not with testosterone). In contrast, the relaxin binding in the rat heart was not affected by castration or sex steroid treatment. We conclude that specific and high-affinity relaxin receptors exist in the atrium of both the male and female rat heart and that these are regulated differently than the relaxin receptors in the uterus.

Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor.

Recombinant human growth hormone (HuGH) and human prolactin (HuPRL), but not GH of bovine or porcine origin, prime human neutrophils for enhanced superoxide anion (O2-) secretion. Since HuGH, but not GH of other species, effectively binds to the HuPRL receptor (HuPRL-R), we used a group of HuGH variants created by site-directed mutagenesis to identify the receptor on human neutrophils responsible for HuGH priming. A monoclonal antibody (MAb) directed against the HuPRL-R completely abrogated O2- secretion by neutrophils incubated with either HuGH or HuPRL, whereas a MAb to the HuGH-R had no effect. The HuGH variant K172A/F176A, which has reduced affinity for both the HuGH-binding protein (BP) and the HuPRL-BP, was unable to prime human neutrophils. This indicates that priming is initiated by a ligand-receptor interaction, the affinity of which is near that defined for receptors for PRL and GH. Another HuGH variant, K168A/E174A, which has relatively low affinity for the HuPRL-BP but slightly increased affinity for the HuGH-BP, had much reduced ability to prime neutrophils. In contrast, HuGH variant E56D/R64M, which has a similar affinity as wild-type HuGH for the HuPRL-BP but a lower affinity for the HuGH-BP, primed neutrophils as effectively as the wild-type HuGH. Finally, binding of HuGH to the HuPRL-BP but not to the HuGH-BP has been shown to be zinc dependent, and priming of neutrophils by HuGH was also responsive to zinc. Collectively, these data directly couple the binding of HuGH to the HuPRL-R with one aspect of functional activation of human target cells.

Growth hormone and renal glutamine and glutamate handling.

Growth hormone administration effects a positive nitrogen balance in part by recycling glutamine nitrogen as glutamate at the expense of ureagenesis. The study presented here focuses on the response of the isolated perfused hypophysectomized rat kidney to acute growth hormone administration during infusions of either glutamine or glutamate. Growth hormone at 50 nM acutely decreases the renal utilization of both glutamine and glutamate while enhancing reabsorption of the latter. During glutamine infusions of either 1,000 or 500 nmol/min, growth hormone markedly reduced net glutamine utilization by 55% at the high loads and reversed utilization to release at the lower load; associated with decreased glutamine utilization was reduced ammonium production and increased glutamate release. Although glutamine reabsorption was unchanged, glutamate reabsorption increased and NH4+ excretion decreased. During glutamate infusion of 180 nmol/min, growth hormone reduced glutamate utilization 66%, the residual utilization matching increased glutamate reabsorption was associated with enhanced bicarbonate reabsorption and a redistribution of NH4+ release into the urine; all three responses were eliminated by amiloride. These responses to growth hormone are consonant with reduced glutamate oxidation underlying decreased glutamine utilization and accelerated luminal Na+-H+ exchange mediating luminal transport, events that are conceivably interrelated.

Lack of cardiovascular and vasopressin responses to human relaxin in conscious, late-pregnant rats.

Measurements of arterial pressure, heart rate, and plasma vasopressin were obtained in unanesthetized late-pregnant rats after administration of human relaxin (hRlx) alone or in conjunction with hemorrhage. Forty-two timed-pregnant rats were prepared with chronic femoral cannulas on the 17th day of pregnancy for measurements on the 19th day. In three separate sets of experiments, mean arterial pressure and heart rate were measured for 10 min before administration of 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle and for 20 h thereafter; plasma vasopressin was determined 20 min before and 3 min after administration of hRlx or vehicle and 20 min after performing a 15-ml/kg 3-min hemorrhage. Neither mean arterial pressure nor heart rate was significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. Plasma vasopressin was not significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. The decreases and subsequent compensatory changes in mean arterial pressure and heart rate after hemorrhage and the increases in plasma vasopressin were not significantly different among rats administered vehicle or hRlx.

Growth hormone accelerates tubular acid secretion.

The effect of growth hormone on tubular H+ secretion by the hypophysectomized and intact rat was studied in the isolated functioning kidney. Net acid secretion was estimated as the sum of HCO3- absorption plus NH+4 excretion. Kidneys from either intact or hypophysectomized rats were isolated and perfused over a 90-min time course during which either recombinant human growth hormone (GH), insulin-like growth factor-1 (IGF-1), porcine insulin, or vehicle was added; hormone response was then compared with the time controls. Compared with kidneys from intact rats, hypophysectomized rat kidneys exhibited a marked acidification defect, net H+ secretion, 13,530 +/- 600 vs. 17,860 +/- 810 (SE) nmol/ml of glomerular filtrate (GF). Administering GH (50 nM) increased net H+ secretion within 15 min in both hypophysectomized and intact groups to a maximum of 17,950 +/- 910 and 20,960 +/- 1,100 nmol/ml GF, respectively; neither insulin nor IGF-1 (50 nM) was able to mimic GH's effect. Addition of 1 mM amiloride completely abolished the GH-accelerated acid secretion and greater than 70% of the basal net acid secretion rate. Furthermore, GH-enhanced volume absorption was also abolished by amiloride, although neither NaCl nor glutamine absorption was affected. GH-accelerated acid secretion and coupled volume absorption could be observed at concentrations as low as 3.5 nM with half-maximal effect at 12 nM, which is within the range of GH concentration achieved during episodic GH surges. Finally administering GH in vivo to hypophysectomized rats enhanced net acid secretion and urinary acidification, consistent with accelerated tubular H+ secretion as one physiological expression of GH action.