Biomedical subjects

E Zerath

Publications and source records attributed to E Zerath.

27 records · Page 2Linked to original sources

PubMed1994

Changes in rat atrial ANF granules induced by hindlimb suspension.

It is well known that the heart releases a factor called ANF (atrial natriuretic factor) or ANP (atrial natriuretic peptide) capable of inducing rapid diuretic and natriuretic actions. This factor is stored in secretory granules mainly located in myocytes in both atria. The main secretory stimulus is the distention of the atrial cavity resulting, for example, from enhanced venous return. However, the cellular events which occur after the stimulation remain to be clarified. The aim of this investigation was to study the intra-cellular events preceding the ANF release, using the rat hindlimb suspension as model of stimulation. In this model, Wistar rats were placed in a 30 degrees anti-orthostatic position and a blood shift towards the heart was obtained. Different durations (1/4 h, 1/2 h, 3/4 h, 1 h, 2 h and 6 h) were studied. The ANF plasma level was investigated by Radio Immuno Assay and granule immunoreactivity was measured by counting gold particles on micrographs. The ANF plasma level was significantly increased (+60%) after 1 h of suspension. The response was transient and then decreased to basal values. Morphological criteria established at the beginning of this study, and measured throughout the experiment, were found transiently modified after suspension. The surface of the perinuclear area was transitory enlarged by 36% 30 min after suspension. Moreover, in the same time immunoreactivity of the secretory granules was enhanced without changes in granule size. These results suggest an increase in the ANF synthesis and storage in the granules during the stimulation. However, the cellular regulatory mechanism of the ANF synthesis which could explain the transitory aspect of these events, requires further investigation.

Animals↗

PubMed1994

Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats.

We previously found that the inhibition of bone formation and trabecular osteopenia induced by skeletal unloading in rats are associated with reduced proliferation of osteoblastic cells lining the bone surface. In this study, we examined the effects of insulin-like growth factor-I (IGF-I) on trabecular bone formation, bone mineral density, and proliferation of marrow-derived osteoblastic cells in unloaded rats. Skeletal unloading of hind limbs was induced by tail suspension, and recombinant human IGF-I was administered at two different doses (1.3 or 2.0 mg/kg.day) in control and unloaded rats by continuous infusion for 14 days. Treatment with IGF-I had no effect on plasma glucose levels, body weight, or longitudinal bone growth. The double calcein-labeled surface, bone formation rate, and trabecular number measured at the tibial metaphysis were lower in unloaded rats compared to controls and were increased after IGF-I treatment. The increased number of bone-forming sites induced by IGF-I was associated with partial prevention of trabecular bone loss in unloaded rats. In contrast to the beneficial effects of IGF-I on bone formation and bone mineral content in unloaded rats, IGF-I had no effect in control rats. To evaluate the cellular mechanisms of action of IGF-I, marrow stromal cells were derived from the tibia of unloaded and control rats and studied in vitro. Unloading was associated with a decreased proliferation of alkaline phosphatase-positive (ALP+) marrow stromal cells. Treatment with IGF-I increased the number of ALP+ cells in unloaded rats, but not in control rats. IGF-I treatment increased ALP activity and osteocalcin production by marrow-derived cells in suspended and control rats, suggesting that IGF-I stimulated the proliferation and differentiation of osteoblast precursor cells. These results indicate that IGF-I infusion enhanced the recruitment of osteoblastic cells, increased trabecular bone formation, and partially prevented trabecular bone loss in unloaded rats, which supports the hypothesis that IGF-I may mediate in part the effects of loading on bone formation.

Alkaline Phosphatase↗

PubMed1993

Bone morphometric changes in adjuvant-induced polyarthritic osteopenia in rats: evidence for an early bone formation defect.

Adjuvant polyarthritis (AP) in rats is known to result in extensive bone loss. This study investigates the mechanisms responsible for the early trabecular osteopenia evaluated at a single point in time--2 weeks after adjuvant injection--in the hindpaw of female Lewis rats using biochemical and histomorphometric methods. At this early point in time, the inflammation was generalized (inflammatory score, 20; albumin/globulin, -80% versus control). Histomorphometric analysis of the noninjected femur showed that the trabecular bone volume was significantly decreased (-28% versus control) in both proximal and distal parts, and the femur growth rate was unaffected. The trabecular osteopenia was associated with a 90% decrease in osteoid surface and a concomitant thinning (-19%) of the trabeculae. Both the double-fluorescence-labeled surface and the osteoblast surface were also markedly decreased (-75%). In addition, the mineral apposition rate was reduced (-50%) and the bone formation rate was decreased by as much as 90%. The trabecular bone volume was decreased in relation with the extent of double-fluorescence labeling (r = 0.38, p = 0.03) and bone formation rate (r = 0.42, p = 0.01), suggesting that the generalized osteopenia resulted from the reduced bone formation. This was associated with a 26% reduction in plasma osteocalcin. Neither the osteoclast surface nor the number of osteoclasts was consistently affected. However, urinary hydroxyproline was increased by 100-200%, which likely reflected the cartilage and bone destruction at the site of injection. The present data show that the early extensive osteopenia observed 2 weeks after AP induction in rats results from defective bone formation with unchanged bone resorption. The role of cytokines in such an inhibitory effect on bone formation remains to be determined.

Animals↗

PubMed1993

The effects of a 5-month physical training on iliac bone morphology in monkeys.

The present study was designed to provide data on the effects on bone of 5 months of daily exercise in nonhuman primates. The subjects were five male rhesus monkeys with mature skeletons with a body mass of 8-10 kg. The exercise schedule selected to provide endurance training was a daily continuous 1-h climbing task. An iliac crest bone biopsy was performed prior to and at the end of the physical training. The histomorphometric bone study was based upon bone mass and bone cell activity measurements made on nondecalcified bone slides, using trichromic and fluorescent labelling techniques. Results showed a decrease in bone formation, resulting in reduced bone mass at the end of the 5 months. This effect is suggested to be related to the unphysiological climbing regimen imposed on these animals which are naturally used to short periods of rapid exercise. From these investigations it was concluded that even if it is well tolerated, long-term physical endurance training can induce bone loss in primates. Further investigations are needed to determine with accuracy the relationships between bone physiology and physical exercise, and particularly with regard to its type, intensity and duration.

Animals↗

PubMed1993

Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells.

The effects of skeletal unloading on osteoblastic cells were evaluated in tail-suspended rats. Hindlimb elevation for 14 days induced osteopenia, decreased histomorphometric indexes of bone formation in tibial metaphysis, and reduced plasma osteocalcin and alkaline phosphatase (ALP) levels compared with controls. The in vitro proliferation of osteoblastic cells isolated from the endosteal bone surface of suspended tibias was decreased by 42 and 31% at 2 and 4 days of culture, respectively, compared with controls, as shown by [3H]thymidine labeling and cell number. The proliferation of ALP-positive marrow stromal cells was also decreased by 20-24% at 1 and 2 days of culture. However, ALP activity in bone-derived cells and marrow stromal cells was not different in unloaded and control rats, and the number of bone cells synthesizing osteocalcin, osteonectin, and type I or type III collagen was identical in the two groups. The results indicate that the inhibition of bone formation induced by skeletal unloading is related to a decreased proliferation of putative osteoblast precursor cells present along the endosteal bone surface and in the marrow stroma.

Alkaline Phosphatase↗

PubMed1992

Bone mass and bone cellular variations after five months of physical training in rhesus monkeys: histomorphometric study.

Five Rhesus Monkeys (Macaca mulatta), a suitable nonhuman model, performed 5 months of rope-climbing exercise. Duration of the training sessions was progressively increased to reach 1 hour/day after 1 month of training and was maintained until the end of the experiment. Bone mass parameters, bone resorption, and bone formation activity were measured by histomorphometric analysis on iliac crest bone biopsies before and after the experiment. Mineral apposition rate was measured in cortices and trabecular bone after double calcein labeling. Five months of rope-climbing exercise had determined a significant decrease of bone volume with a slight decrease of the number and thickness of trabeculae. This might induce an alteration of biomechanical properties of bone. These architectural modifications were associated with a nonsignificant decrease of bone resorption activity. But the main effect of training was an important decrease of bone formation activity without change of the mineral apposition rate. Endurance exercise at low intensity has determined a decreased bone turnover with osteoblastic depression. This animal experiment points out that exercise modalities might be important in the bone response to training and should be carefully defined for preventive use in humans.

Animals↗

PubMed1990

Gastric lesions secondary to long-distance running.

Gastrointestinal disorders have been reported during long-distance running. The purpose of this study was to evaluate the effects of prolonged exercise on the upper digestive tract. Seven subjects were submitted to a standard endoscopic examination of the upper digestive tract before and after long-distance running (range 18-50 km). Mucosal biopsy specimens were taken during all endoscopies. After running, all runners had histologically pathological features in the stomach. Vascular lesions were present in the chorion in six subjects after running, with the intensity of the lesions ranging from congestion to hemorrhage. Postexercise histological examination also showed a decrease in mucosal secretion. These lesions secondary to prolonged exercise indicate the presence of hemodynamic perturbations in the upper digestive tract.

Adult↗

PubMed1990

Five months of daily standardized exercise for sedentary monkeys.

A system to physically exercise rhesus monkeys is described, based on their natural capacity to climb. It is composed of an enclosure where a motor-driven rope is continually going down. The two stage training to this task is easily performed. The total work of each run, evaluated with the weight of the animal and the distance climbed, may be very stable. It was used to provide five sedentary monkeys with daily physical training for five months.

Animals↗

PubMedDate not supplied

Effects of exogenous growth hormone on bone mineralization and remodeling and on plasma calcitriol in intact pigs.

Growing pigs were given subcutaneous (SC) injections of 40 micrograms porcine GH/kg body weight (BW) or its vehicle twice daily for 2 months. Animals were pair-fed with a diet containing 1.1% Ca, 0.6% P, and 1000 IU vitamin D3/kg. At slaughter, several bone characteristics including histomorphometric data (using double tetracycline labeling) were measured on tibia and metacarpals. GH accelerated growth, with greater (p < 0.01) tibial and metacarpal weights, greater tibial length (p < 0.01) and diameters (outside and inside, p < 0.01), and greater tibial ash weight (p < 0.02) in GH-treated pigs than in controls. The similar values of apparent bone density (weight/volume) and ash/bone volume or ash/dry matter in the two groups suggest adequate coupling between bone growth and mineralization in GH-treated pigs. Histomorphometric data for the distal metacarpal metaphysis indicated greater trabecular bone volume (p < 0.01), osteoblastic surface (p < 0.01), and mineral apposition rate (p < 0.05) in GH-treated pigs. The osteoclast surface, lacuna depth, and osteoid-related parameters in GH-treated and control pigs were similar. The plasma PTH of the two groups of pigs were similar throughout the experiment. These data and the elevated plasma alkaline phosphatase activity (p < 0.05) in GH-treated pigs suggest that GH specifically affects bone formation. GH had no effect on the plasma 25-OH vitamin D3 but 1,25(OH)2 vitamin D3 (calcitriol) was higher (p < 0.01) in treated pigs throughout the experiment. This suggests that calcitriol may help adapt bone mineralization to accelerated bone formation during growth hormone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗