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Biomedical subjects

S K Abbas

Publications and source records attributed to S K Abbas.

15 recordsLinked to original sources
PubMed1992

Parathyroid gland hormones in the skeletal development of the ovine foetus: the effect of parathyroidectomy with calcium and phosphate infusion.

It has been confirmed that the foetal parathyroid glands are important in development and that thyroparathyroidectomy (TXPTX) of the ovine foetus with thyroxine (T4) replacement leads to hypocalcaemia, retarded skeletal development, depressed calcification and rickets, relative to thyroidectomy plus T4 replacement. Histomorphometric and biochemical (urinary excretion of deoxypyridinoline) indices of bone resorption are also reduced. However, skeletal calcification can be restored to normal by long-term infusion of the TXPTX foetuses with phosphate and calcium sufficient to normalise the plasma Ca2+ x Pi ion product. Nevertheless, depressed resorption, reduced osteoblast numbers and delayed development persisted. The evidence suggests that the abnormally low number of resorption cavities and osteoclasts may result from the reduction in circulatory parathyroid-hormone-related protein consequent upon the removal of the foetal parathyroid glands and that this hypercalcaemic factor has a direct effect upon the process of resorption and primary trabecular remodelling of the foetal skeleton.

Amino Acids↗
PubMed1992

The effects in the rat of two fragments of parathyroid hormone-related protein on uterine contractions in situ.

Synthetic parathyroid hormone fragment PTH(1-34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone-related protein fragment PTHrP(1-34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine-stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75-86 amide) (10(-9)-10(-7) M) was without effect, synthetic hPTHrP(1-34) (10(-9)-10(-7) M) was capable of inhibiting, in a dose-related fashion, uterine muscle contractions precontracted with 10(-6) M-acetylcholine. In a second series of experiments the bovine PTH(3-34) fragment itself was shown to have no stimulatory effect on acetylcholine-stimulated contractions. Also this fragment in an equimolar concentration (10(-7) M) failed to antagonize the effects of PTHrP(1-34) on acetylcholine-stimulated uterine contractions. However, a 100-fold excess molar concentration of bPTH(3-34) (10(-6) M) completely abolished the inhibitory action of hPTHrP(1-34) (10(-8) M) on acetylcholine-stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1-34) and PTHrP(1-34) on uterine contractions depends on the integrity of the amino-terminal region of the molecule.

Acetylcholine↗
PubMed1991

Stimulation of calcitonin secretion in the pig by calcitonin gene-related peptide.

Pig thyroid glands were surgically isolated in situ and perfused with autologous blood to which was added known concentrations of calcitonin gene-related peptide (alpha CGRP). When thyroids were perfused with measured concentrations of CGRP within the range of 0.6-600 nM, the secretion rate of calcitonin (CT) was stimulated while the release of T3, T4, and somatostatin remained unchanged. Specific binding of 125I-CGRP to pig thyroid plasma membranes was demonstrated, and binding was inhibited by unlabelled CGRP but not by CT or by other peptides unrelated structurally to CGRP. The findings indicate that the pig thyroid gland contains plasma membrane binding sites for CGRP and that CGRP is capable of stimulating the secretion of CT.

Animals↗
PubMed1991

Parathyroid hormone-related protein(50-69) and response to pamidronate therapy for tumour-induced hypercalcaemia.

A region-specific radioimmunoassay has been employed to measure levels of immunoreactive parathyroid hormone-related protein(50-69) (iPTHrP(50-69)) in patients with tumour-induced hypercalcaemia (TIH). This assay is based on an antiserum raised against synthetic human PTHrP(50-69). The assay showed no cross-reactivity with human or bovine parathyroid hormone(1-84). The effect of a single dose (60 mg) of pamidronate was studied in 25 consecutive patients with TIH. All were rehydrated prior to treatment. All but 2 patients (8%) became normocalcaemic after treatment; both of these had very high levels of iPTHrP(50-69). Time to achieve normocalcaemia, as an index of relative resistance to pamidronate, correlated positively with pretreatment level of iPTHrP(50-69). Absence of radiological evidence of bone metastases also predicted relative resistance to pamidronate. In this study, iPTHrP(50-69)-induced osteoclastic bone resorption was a more important mechanism in the causation of TIH than PTHrP-induced renal reabsorption of calcium as assessed by the renal thresholds for calcium and phosphate.

Adult↗
PubMed1990

Stimulation of ovine placental transport of calcium and magnesium by mid-molecule fragments of human parathyroid hormone-related protein.

Perfusion in situ of the placenta of intact or previously parathyroidectomized fetal lambs has been used to assess the ability of three mid-molecule fragments of the human parathyroid hormone-related protein (PTHrP) molecule to stimulate the placental transport of calcium and magnesium. PTHrP(67-86 amide) was most effective but some activity was also shown by PTHrP(75-86 amide) and by PTHrP (75-84) in decreasing order. This placental action of PTHrP(67-86 amide) was rapid and could be observed using the placenta from an intact fetus, whereas it was necessary to use the placenta from a previously parathyroidectomized fetus to demonstrate stimulation of placental calcium transport by PTHrP(1-84). PTHrP(67-86 amide) may resemble the molecule that activates the placental calcium pump.

Animals↗
PubMed1990

Fetal magnesium homeostasis in the sheep.

The fetal plasma magnesium concentration exceeds that of the mother but the difference is small compared to that of ionized calcium concentration. Although not fully independent of changes in maternal magnesaemia, fetal magnesaemia showed a high degree of autonomy during both hypermagnesaemic and hypomagnesaemic changes induced in the ewe. As with calcium, the placental gradient is reversed after fetal thyroparathyroidectomy (TXPTX) with thyroxine replacement. During perfusion in situ of the placenta from such TXPTX fetuses isolated from the fetus itself, a stable positive placental gradient of magnesium concentration could be re-established between the perfusing blood and the maternal circulation. As with calcium, this gradient could be increased by fetal calf parathyroid extract, parathyroid hormone-related protein (PTHrP 1-141), PTHrP (1-84) but not by PTHrP (1-34). It was concluded that a mid-molecule portion of PTHrP can stimulate a putative placental pump which is responsible for the gradients of both calcium ions and magnesium across the ovine placenta.

Animals↗
PubMed1990

Measurement of parathyroid hormone-related protein in extracts of fetal parathyroid glands and placental membranes.

A radioimmunoassay based on an antiserum to human parathyroid hormone-related protein PTHrP(1-16) was used with PTHrP(1-34) standard to measure the concentration of immunoreactive PTHrP in extracts of fetal parathyroid glands from lambs and calves and also placental membranes obtained from several species, including man. Dilution curves from these sources were parallel to those obtained for PTHrP(1-34) standard. It was demonstrated that this parallelism was not the result of tracer damage caused by enzymic activity in the tissue extracts. Extracts of human placental membranes were subjected to high-pressure liquid chromatography with a linear acetonitrile gradient. Co-elution of cytochemical biological activity with 125I-labelled PTHrP(1-34) was noted. These results provide further evidence for both the fetal parathyroid glands and the placenta containing material resembling PTHrP which may be responsible for sustaining the activity of the placental calcium pump which maintains the fetus hypercalcaemic relative to its mother.

Animals↗
PubMed1989

The parathyroid glands in the skeletal development of the ovine foetus.

The ionized plasma calcium concentration in foetal lambs during the last third of gestation is greater than that in the ewe. Since foetal plasma immunoreactive parathyroid hormone is less than that in the ewe the role of the foetal parathyroid glands is not clear. The effects of foetal parathyroidectomy (PTX) on the foetal:maternal gradient and on skeletal development are examined. The histomorphometry and ash content of six PTX lambs was compared with that of 11 intact animals. A reversal of the plasma ionized calcium gradient took place within 3 days without significant change in the foetal plasma inorganic phosphate or 1,25-dihydroxycholecalciferol content. Skeletal changes consistent with rickets were observed and increased in severity with the time after PTX. It is concluded that the foetal parathyroid glands play an important role in placental calcium transfer and skeletal calcification. However, the agent may be a hypercalcaemic substance other than parathyroid hormone.

Animals↗
PubMed1989

Comparison of effects of verapamil, low calcium diet and betamethasone on duodenal calcium absorption efficiency in the chick.

The results indicate that oral administration of verapamil for 2 weeks to the chick is followed by an increase in the efficiency of the duodenal absorption of calcium. In these chicks both a decrease in serum calcium level and an increase in the activity of renal 1 alpha-hydroxylase were observed. The increased calcium absorption following prolonged treatment with verapamil resembles that induced by a low calcium diet. The mechanism of both responses presumably involves an increased production of 1,25-dihydroxyvitamin D3. Both verapamil- and low calcium diet-induced adaptations are capable of overcoming the inhibitory action of betamethasone on intestinal calcium absorption. No effects on calcium absorption were noted if verapamil was administered intraperitoneally which suggests that verapamil exerts its action directly on the intestinal mucosa.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1989

Stimulation of ovine placental calcium transport by purified natural and recombinant parathyroid hormone-related protein (PTHrP) preparations.

Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo.

Animals↗
PubMed1988

The involvement of calmodulin in the secretion of calcitonin from the porcine thyroid gland.

The effect of the calmodulin antagonist W7 has been studied in the pig in vivo by measuring directly the secretion rate of calcitonin (CT) in the thyroid venous blood after surgical isolation of the thyroid and subsequent perfusion of the gland in situ. Over the concentration range of W7 9-100 mumol/l in the perfusing plasma there was a significant increase in CT secretion rate associated with the addition of W7 to the perfusing blood. There was no significant change in the perfusing plasma calcium concentration. It is suggested that calmodulin plays an important role in calcium homeostasis within the porcine thyroid C-cell.

Animals↗
PubMed1987

Effects of danazol on mineral homeostasis in normal postmenopausal women: preliminary communication.

The effects of danazol on calcium homeostasis in normal postmenopausal women was examined in a 14-day study utilizing a dosage of 800 mg per day. Danazol caused significant falls in plasma ionized calcium and in the fasting urinary calcium/creatinine ratio, indicating inhibition of bone resorption. Retention of phosphate was also observed as expected with this anabolic agent. The plasma total alkaline phosphatase was also depressed by the drug, which had no effect on hepatocellular function as measured by plasma AST. Certain effects induced by treatment with danazol were still apparent two weeks after cessation of treatment. The drug was well tolerated and androgenic side effects were not seen. It is suggested that the minimal dose regimen of danazol which exerts a calcium-sharing effect should be identified, and that this regimen should be considered for use in a prospective study of the effects of danazol on bone mineral content in the postmenopause.

Bone Resorption↗
PubMed1987

Plasma vitamin D-binding protein and free 1,25-dihydroxyvitamin D3 index in pregnant ewes and their fetuses in the last month of gestation.

A radioimmunoassay for ovine vitamin D-binding protein (DBP) has been developed. This assay can also effectively measure DBP in goat plasma. A suitable ovine DBP antiserum raised in a rabbit produced a single monospecific line of precipitation when reacted against purified sheep DBP and sheep plasma. The preliminary purification of 125I-labelled ovine DBP was carried out using adsorption chromatography, and the final purification immediately before addition to the assay tubes was achieved by high-pressure liquid chromatography. Displacement of 125I-labelled ovine DBP by dilutions of sheep and goat plasma or standard DBP gave parallel curves, and only weak competition was observed with calf and pig plasma. The assay detected as little as 26 pmol DBP/l with intra- and interassay coefficients of variation of 3 and 14% respectively. The mean plasma concentration of DBP in nine pregnant sheep (110-120 days of gestation) was 8.7 +/- 0.3 (S.E.M.) mumol/l. These levels were significantly (P less than 0.02; paired t-test) higher than those in matched fetal plasma (6.7 +/- 0.4 mumol/l) obtained in utero through a catheter in a carotid artery. Plasma DBP concentrations in pregnant sheep were also significantly (P less than 0.02) higher than in five normal non-pregnant sheep (6.8 +/- 0.5 mumol/l). The mean concentrations of total 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) in maternal and fetal plasma were 92.0 +/- 8.7 pmol/l and 152.5 +/- 18.0 pmol/l respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The effect of fetal thyroparathyroidectomy on the transport of calcium across the ovine placenta to the fetus.

The ovine fetal placenta has been perfused with autologous fetal blood under controlled conditions in eleven experiments in which the fetus was first removed. Eight of these experiments involved four pairs of twins, one lamb of which had been thyroparathyroidectomized (TXPTX) three to seven days earlier. By this time the normal placental calcium gradient from mother to fetus had either decreased or been reversed. The mean rate of transport of calcium from the mother was unchanged by previous fetal TXPTX, but the final calcium gradient achieved from the mother to the perfusing blood was significantly less than with placentae from intact fetuses. No significant alteration in fetal plasma I,25-dihydroxyvitamin D (I,25(OH)2D) concentration was observed as a result of the fetal TXPTX, indicating that hypocalcaemia can compensate for the lack of PTH in fetal production of I,25(OH)2D. Fetal thyroidectomy with replacement of thyroxine did not lead to reversal of the placental calcium gradient, indicating that calcitonin was not involved. It is suggested that in the ovine fetus, parathyroid hormone promotes the active transport of calcium from mother to fetus, so that in its absence the fetus must obtain its calcium for growth by reducing its calcaemia and thereby allow net diffusion of calcium to replace the action of the placental calcium pump. The price paid for this compensation is marked hypocalcaemia and defective calcification of osteoid.

Animals↗