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Biomedical subjects

V Coxam

Publications and source records attributed to V Coxam.

At least 55 records · Page 3Linked to original sources

[Physical exercise and the skeleton].

The skeleton provides more than only a framework for the body. Bone is a calcified conjunctive tissue sensitive to various mechanical stimuli, mainly to those resulting from gravity and muscular contractions. Numerous animal and human studies demonstrate the importance of weight-bearing physical activity as well as mechanical loading for maintaining skeletal integrity. Lack of weight-bearing activity is dangerous for the skeleton: a decrease in bone mineral density (BMD) has been demonstrated in animals and humans under conditions of weightlessness or immobilization. Other studies have also reported a lower vertebral BMD among young amenorrheic athletes than among athletes with regular cycles and/or non athletes. The main factor responsible for this lower BMD in the amenorrheic athletes is the persistent low level of endogenous estrogen observed among these women. However this does not represent a premature and irreversible loss of bone mass since the resumption of menses following a decrease in training is the primary factor for a significant increase in vertebral BMD in these formerly amenorrheic athletes. A weight-bearing exercise is likely to be more beneficial at weight-bearing than at non weight-bearing sites, and hypogonadism resulting from very intensive training and exercise is more detrimental to trabecular than cortical bone. Bone deficit at non weight-bearing sites may be attenuated by maintenance of body weight. Nevertheless the etiology of "stress fractures" among athletes remains poorly understood, and the exact relationship between soft tissue mass and BMD is not clear. Osteoporosis, the most common bone disorder in France, is a pathological condition associated with increased loss of bone mass, resulting in a greater risk of fracture. Although symptoms of osteoporosis do not generally occur until after menopause, recent evidence suggests that bone loss starts much earlier in life. Therefore osteoporosis might be prevented by increasing peak bone mass and/or by slowering bone loss after menopause. Exercise such as resistance training or weight-bearing activities like running or walking have an osteogenic effect on increasing BMD in young people, and the decrease in BMD is slower in exercised than in non-exercised post-menopausal women. Nevertheless the influence of the length and of the intensity of such physical activities remain to be determined.

Animals↗

[Physiology of intestinal absorption of phosphorus in animals].

Intestinal absorption of inorganic phosphorus. In most mammalian species inorganic phosphorus (P) is absorbed at the duodenal and jejunal level. However in horses some P is absorbed from the large intestine, whereas in ruminant animals some absorption also takes place in the forestomachs. The structure of the putative phosphate-sodium carrier of the brush border from enterocytes still awaits identification. P absorption is modulated both by endocrine (calcitriol, triiodothyronine) and nutritional factors (minerals of the diet, chemical form of phosphorus). Regulation of salivary P secretion, intestinal absorption of P in ruminants, and its adaptation to diets high or low in P are still poorly understood. Such studies would probably help to decrease the cost of P supplementation in farm animals.

Animals↗

Short communication: parathyroid hormone-related peptide does not stimulate phosphate placental transport.

It has been demonstrated that parathyroid hormone-related peptide (PTHrP) stimulates calcium (Ca) placental transport. Ca and inorganic phosphorous (P) metabolisms are intimately linked. Thus we have studied the influence of PTHrP on P placental transport in ewes. In our experimental paradigm, synthetic human PTHrP (1-86) fragment intravenously injected in six single chronically catheterized fetuses (3 x 1 micrograms/fetus/day, from day 129 to day 140 of gestation) had no significant effect upon P placental transport which was 131 +/- 6 and 129 +/- 9 mg/kg fetal weight/day in treated and control fetuses, respectively.

Animals↗

Preserved bone mass in ovariectomized rats treated with parathyroid-hormone-related peptide (1-34) and (107-111) fragments.

The effect of synthetic human PTHrP (1-34) or (107-111) fragments on bone loss was studied in rats, one month after ovariectomy (OVX). Four groups of 7-8-month-old rats were treated sc daily for 13 d with PTHrP (1-34) or (107-111) at the dose of 1 or 3 nmol/100 g body weight. Sham-operated (SHO) and control OVX rats received solvent alone. In our conditions, at the lowest dose, neither (1-34) nor (107-111) fragments had any significant effect. However, at the dose of 3 nmol/100 g daily for 13 d both treatments significantly increased femoral dry weight, ash weight, Ca content and densitometry of the femur. The effect of PTHrP (1-34) mainly resulted from increased cortical and trabecular bone (% recovery: 98.25 and 105.23%, respectively). For the PTHrP (107-111) fragment, a positive effect was only demonstrated on the cortical bone (98.25% recovery). The results of this study demonstrate that both hPTHrP (1-34) and (107-111, osteostatin) fragments are positive for bone when administered at the dose of 3 nmol/100 g body weight/d for 13 d to adult OVX rats.

Animals↗

[Animal models of post-menopausal osteoporosis].

Osteoporosis is a disease characterized by low bone mass, microarchitectural deterioration of bone tissue leading to enhanced bone fragility, and a consequent increase in fracture risk. In humans estrogen deficiency following menopause is associated with a more or less intense osteopenia. In some subjects, such a decrease in bone mass induces osteoporosis. Several animal models (ovariectomized female dogs, pigs and monkeys) are used to study the etiology, prophylaxis and treatment for osteoporosis. Nevertheless, the changes in bone metabolism following estrogen deficiency are very similar in rats and humans. Thus, the ovariectomized rat is the most frequently used model for such studies.

Animals↗

Growth hormone (GH) secretory pattern and GH response to GH-releasing factor (GRF) or thyrotropin-releasing hormone (TRH) in newborn foals.

The present study was undertaken to assess GH secretory profiles in 12 light-breed foals and their dams during forty days after delivery, and the possible influence of GRF and TRH on plasma GH concentrations in these newborn foals. GH secretory pattern was pulsatile in one day- as well as in forty days-old foals. The number of secretory spikes (10 per 24 h) did not vary between days 1 and 40. In the same times, GH secretion did not show any circadian rhythm either in foals or in their dams. Mean daily plasma concentrations (measured through blood samples collected every 20 min for 24 h) were lower in mares (3.4 +/- 0.3 ng/ml) than in their foals (7.4 +/- 0.9 ng/ml; P < 0.05). This difference resulted from both a lower number of GH spikes per 24 h (5 +/- 2 vs 10 +/- 1; P < 0.01) and from a lower pulse amplitude average (8 +/- 5 vs 16 +/- 1; P < 0.05). In three days- and in six days-old foals, synthetic human GRF (0.3 microgram/kg body wt, i.v.) significantly increased plasma GH concentrations. TRH (3 micrograms/kg body wt, i.v.) did not significantly modify plasma GH.

Animals↗

Plasma 1,25-dihydroxyvitamin D, insulin-like growth factor-1, calcium, magnesium and phosphorus concentrations in pregnant beef cows and calves from a herd with a known history of congenital joint laxity and dwarfism.

An investigation was undertaken to ascertain the possibility of a relationship between calcium, inorganic phosphorus, magnesium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and insulin-like growth factor-1 (IGF-1) concentrations in blood plasma and occurrence of congenital joint laxity and dwarfism (CJLD) in young cattle. Pregnant cows were fed hay (30 cows) or grass silage (122 cows) during winter months (October 15 to calving in March). Blood samples were taken from cows on seven occasions during the experiment and 48 hours after calving, and from calves at birth, and at seven, 14 and 56 days old. Five per cent of calves born (six of 122) to cows fed grass silage and none born to cows fed hay were affected by CJLD. The diet and health status of calves were not significantly (P greater than 0.05) associated with the plasma concentration of 1,25(OH)2D. The plasma calcium concentration declined with age of the calves (P less than 0.05) but was not affected by the occurrence of CJLD. Plasma phosphorus and magnesium concentrations in calves born to cows fed silage were higher (P less than 0.05) than in those born to cows fed hay. At birth and seven days old, plasma phosphorus concentrations were higher (P less than 0.05) in CJLD-affected calves than in healthy calves but the plasma concentration of IGF-1 was not different (P greater than 0.05). It was concluded that the high plasma phosphorus concentrations in CJLD-affected calves and their dams could be related to the aetiology of the CJLD condition in calves.

Animals↗

Insulin-like growth factor-II increases plasma osteocalcin concentration in newborn lambs.

The influence of GH, IGF-I and IGF-II on plasma 1,25-(OH)2D and osteocalcin (OC) concentrations was studied in four groups of five newborn lambs each. They received a single i.v. injection of either purified bovine GH (1 IU/mg 600 micrograms/kg body wt), synthetic human IGF-I (10 or 200 micrograms/kg body wt) or synthetic human IGF-II (10 micrograms/kg body wt). Five controls were injected the same volume (1 ml) of solvent. IGF-II, but not GH or IGF-I, induced a rapid (1.5 h) and sustained (up to 18 h) increase of serum osteocalcin. This effect of IGF-II on plasma OC concentration was not mediated by 1,25-(OH)2D, which increased in plasma only 18 h after IGF-II injection. These data suggest that IGF-II stimulates, the in vivo secretion of OC by osteoblasts through a mechanism independent of 1,25-(OH)2D. Further studies are necessary to elucidate the mechanism of IGF-II action on osteocalcin synthesis and to explain the late increase of plasma 1,25-(OH)2D after IGF-II injection.

Animals↗

Parathyroid hormone-related peptide increases urinary phosphate excretion in fetal lambs.

The effect of synthetic human parathyroid hormone-related peptide fragment 1-34 (hPTHrP) on plasma concentration and urinary excretion of inorganic phosphorus (P) was compared to that of synthetic bovine PTH fragment 1-34 (bPTH) in four 120- to 130-day-old fetal lambs chronically catheterized in utero. They received by I.V. infusion according to a Latin square design either bPTH (6 nmol per fetus) or hPTHrp (6 nmol per fetus) alone, or after the synthetic analogue [Tyr34]bPTH(7-34)NH2 (12 nmol per fetus). Control fetuses received the same volume of solvent alone. Both bPTH and hPTHrP stimulated diuresis. They induced hypercalcaemia, hyperphosphaturia and hypophosphataemia. The effects of hPTHrP were inhibited by [Tyr34]bPTH(7-34)NH2, indicating that PTHrP might work through the PTH receptor.

Animals↗

The influence of parathyroid hormone-related protein on hepatic IGF-1 production.

Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery. Electromagnetic blood flow probes in the portal vein and hepatic artery allowed continuous measurement of hepatic IGF-1 production. In accordance with a latin square design these calves received iv mesenteric infusion (for 60 min) of calcium (Ca, 0.125 mmol.kg body wt-1), the synthetic human parathyroid hormone-related protein (1-34) fragment (PTHrP, 1 nmol.kg body wt-1), the synthetic analogue [tyr]34-bovine PTH-(7-34) NH2 (2 nmol.kg body wt-1) and PTHrP (1 nmol.kg body wt-1) or solvent alone (1.2 ml.kg body wt-1). Hypercalcaemia observed following Ca infusion had no significant effect on hepatic IGF-1 production. PTHrP induced a slight but significant increase in plasma Ca and IGF-1 concentrations measured in the hepatic vein, without changing blood flows measured in the hepatic artery and portal vein. Thus PTHrP increased hepatic IGF-1 production (15.1 +/- 2.7 nmol.6 h-1.kg body wt-1 vs 4 +/- 1.3 nmol.6 h-1.kg body wt-1 in controls; p less than 0.05). These effects induced by PTHrP were inhibited by the synthetic analogue [tyr]34-bPTH-(7-34) NH2.

Animals↗

Parathyroid hormone-related peptide might stimulate calcium secretion into the milk of goats.

Parathyroid hormone-related peptide (PTHrP) has been shown to stimulate the placental calcium pump in pregnant ewes. Recent studies also suggest a physiological role for this peptide during lactation. In the present work, we have studied the possible role of synthetic human PTHrP(1-34), (1-86) and (140-173) fragments on calcium, inorganic phosphorus and magnesium secretion into milk of four adult goats in early lactation. This was done by measuring differences in calcium, inorganic phosphorus and magnesium concentrations in the carotid artery and superficial epigastric vein, the concentration of these minerals in milk and milk production. Both PTHrP(1-34) and (1-86) fragments stimulated calcium, inorganic phosphorus and magnesium uptake by the mammary gland and secretion into milk, without any significant effect on milk production. Therefore PTHrP might have important physiological roles in the pregnant and/or lactating female, by regulating calcium transport through the placenta and mammary gland.

Animals↗

Developmental changes in plasma apolipoproteins B and A-I in fetal bovines.

Plasma lipid, apolipoprotein (apo) B and apo A-I concentrations were measured in fetal calves in the age range of 4-9 months. The results were compared with those obtained from preruminant calves and cows. The studied lipids and apolipoproteins underwent quantitative underwent quantitative changes during development. Fetal calves, as compared to preruminant calves and cows, had a particularly low apo A-I concentration and a high apo B/apo A-I ratio. Unlike adult animals which have two forms of apo B, fetal calves had only high molecular weight apo B (apo Bh). During fetal development triglyceride, cholesterol and apo B concentrations decreased, but apo A-I concentrations remained constant.

Aging↗

Slow release somatotropin in dairy heifers and cows fed two levels of energy concentrate. 2. Plasma hormones and metabolites.

Fifty Holstein dairy cows (26 primiparous) were used to evaluate effects of level of concentrate and of slow release recombinant bST on plasma hormones and metabolites. Blood was sampled at wk 14 and 20 of lactation, which was 5 and 11 wk after the first bST injection. In addition, at d 3 and 10 after the third bST injection, diurnal profiles of somatotropin and metabolites were studied in 7 bST cows and 5 control cows by blood sampling every 20 min over 6 h. Supplementation by bST enhanced plasma somatotropin and insulin-like growth factor-I but did not significantly affect plasma concentrations of triiodothyronin and insulin. The bST supplementation increased plasma NEFA at wk 14 and reduced uremia at wk 20. Primiparous cows showed higher plasma NEFA and triiodothyronin than multiparous cows at both sampling periods, higher insulin-like growth factor I, and lower beta-hydroxybutyrate at wk 14, and higher glucose and lower insulin at wk 20. In the diurnal kinetic study, bST supplementation did not alter bST spike frequency and duration but increased spike magnitude, the area under the curve above the baseline, and the baseline mean. Sixty-one to 56% of the increase over controls in plasma bST total area was due to increase in the area under the curve above baseline. Preprandial NEFA were increased by bST at d 10.

3-Hydroxybutyric Acid↗

Plasma osteocalcin concentrations in cattle under various pathophysiological conditions.

Plasma osteocalcin (BGP) concentrations were measured using an homologous radioimmunoassay in plasma samples (n = 6-14 per group) from fetal and newborn calves, 16-month-old heifers and bulls, and pregnant lactating cows. The highest values (nM) (62 +/- 3) were measured in fetal calves and the lowest (15 +/- 3) in 9-year-old pregnant and lactating cows. No significant relationship could be demonstrated between plasma BGP and somatomedin C, or 1,25(OH)2D or calcium concentrations. In eight normally calving cows, parturition was followed by a progressive increase in plasma BGP concentration, maximum 3 days after calving. It returned to prepartum values 10 days later. In six parturient hypocalcaemic and paretic cows, hypocalcaemia occurring within 12 h following calving was associated with a prompt and very transient increase in plasma BGP concentrations. These results indicate that osteocalcin might play a role in the regulation of bone metabolism in cattle.

Animals↗

Influence of kinetics of gastric emptying on hepatic IGF1 production in young calves.

Five preruminant calves, fitted with chronically indwelling catheters in the hepatic and portal veins and hepatic artery, were fed two kinds of diet (a conventional clotting milk diet and an incurdled milk diet) or fasted for 24 h. The statistical analysis of the plasma growth hormone (GH; nmol/l) or IGF1 (nmol/l) daily secretory profiles indicated that hormonal levels were very high in fed calves (GH mean values: 0.40 +/- 0.11 and 0.36 +/- 0.10, respectively; IGF1 mean values: 6.65 +/- 0.57 and 7.54 +/- 0.33, respectively). The GH secretory profile observed over a 24-hour period showed 7 secretory spikes without periodicity in both diets. In fasting animals, plasma GH and IGF1 concentrations were very low (0.17 +/- 0.08 and 3.08 +/- 0.36, respectively) and stable, they increased with refeeding (1.51 +/- 0.05 and 7.36 +/- 0.55, respectively). Hepatic IGF1 production (micrograms/kg body weight/day) was 195 +/- 7 in standard milk fed calves and -255 +/- 30 in others. Our results demonstrated that nutritional factors, such as different kinetics of gastric emptying or fasting, may influence hepatic IGF1 production in the conscious newborn calf.

Animals↗

Steroid hormone may modulate hepatic somatomedin C production in newborn calves.

We have studied the possible influence of steroid hormones and a beta-agonist (clembuterol) on hepatic insulin-like growth factor 1 (IGF1) production in young calves. For this purpose nine 20- to 40-day-old Holstein X Friesian male calves were fitted with chronically indwelling catheters in hepatic and portal veins and hepatic artery. Estradiol induced a simultaneous increase in plasma growth hormone (GH nmol/l) and IGF1 (nmol/l) levels (0.35 +/- 0.05 vs. 0.10 +/- 0.01 in control calves; 9.5 +/- 1.0 vs. 5.9 +/- 0.5 in controls, respectively). In the same way, 90 min after starting testosterone treatment, plasma GH levels increased from 0.21 +/- 0.08 to 1.30 +/- 0.40 while plasma IGF1 concentrations began to rise only 240 min after starting infusion (8.4 +/- 1.0) to reach maximal values at 300 min (10.7 +/- 1.1). Cortisol and clembuterol did not significantly modify either plasma GH levels or plasma IGF1 concentrations. Our results indicate that in young calves gonadal steroids exert their anabolic action through GH and IGF1.

Animals↗

Parathyroid hormone and calcitonin may modulate hepatic IGF-I production in calves.

Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery, and with electromagnetic blood flow probes in the portal vein and hepatic artery, allowing continuous measurement of IGF-I hepatic production. According to a latin square design, these calves received iv mesenteric infusion of calcium (Ca2+; 5 mg/kg) or synthetic salmon calcitonin (sCT; 1 microgram/kg), or synthetic bovine parathyroid hormone (1-34) (bPTH; 1 microgram/kg), or solvent alone (1.2 ml/kg). Ca2+, sCT or bPTH had no significant effect on portal vein or hepatic artery blood flow. Hypercalcemia observed following Ca2+ infusion did not significantly modify hepatic IGF-I production. sCT decreased plasma Ca2+, inorganic phosphorus and GH concentrations and hepatic IGF-I production. bPTH induced a slight hypercalcemia and hypophosphatemia. It had no significant effect on plasma GH concentration, but increased significantly hepatic IGF-I production. Thus, the anabolic effects of PTH on bone may be partly mediated through an increase in hepatic IGF-I production.

Animals↗

Synthetic parathyroid hormone-related peptide (1-34) fragment stimulates placental calcium transfer in ewes.

The influence of synthetic parathyroid hormone related peptide (PTHrp) fragments on placental transfer of Ca was studied in four groups of four single ovine fetuses fitted with catheters chronically implanted into their left jugular vein (for injections) and carotid artery (for blood sampling), and used between days 104 and 118 of gestation. The first group received PTHrp(1-34), the second PTHrp(107-138), the third bovine PTH(1-34), and the last (control) group was injected with solvent alone. Each peptide (6 nmol/fetus per day) was injected i.v. three times per day from day 105 until day 116 of gestation. Placental Ca transfer (mmol/24 h per kg fetal wt) from the dam to the fetus was not different in control fetuses (7.1 +/- 0.6) and those given PTHrp(107-138) (7.2 +/- 0.5), but it was significantly increased by bovine PTH(1-34) (8.6 +/- 0.4; P less than 0.05) and by PTHrp(1-34) (10.1 +/- 0.3; P less than 0.01). Both peptides also significantly increased plasma concentrations of 1,25 dihydroxy-vitamin D3 (1,25-(OH)2D). These results indicate that PTHrp(1-34) can stimulate placental Ca transfer by increasing 1,25-(OH)2D synthesis, but also possibly by acting directly upon the placenta.

Animals↗