Hormone Infusion Research Articles

Calcium intake by rats: influence of parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D.

We examined the contribution of the primary hormones of calcium homeostasis to the control of calcium intake in the rat. Male Sprague-Dawley rats with 50 mM CaCl2 solution as their only source of calcium received subcutaneous hormone infusions for 13 days. Parathyroid hormone (PTH; 40, 80, or 160 ng/h) produced sustained dose-related decreases in CaCl2 intake. High doses of calcitonin (CT; 32 or 64 ng/h) increased CaCl2 intake transiently, and low doses (4, 8, or 16 ng/h) had no effect. 1,25-Dihydroxyvitamin D [1,25(OH)2D] in doses > 1 ng/h initially increased CaCl2 intake, but the effects of moderate doses (2 or 4 ng/h) tended to dissipate, and the sustained effect of high doses (8 or 16 ng/h) was to reduce CaCl2 intake. Infusions of combinations of the hormones had effects consistent with their individual actions: there was no evidence for synergy. Based on changes in plasma hormone concentrations, it appeared that most of the infusions had effects within the physiological range. Consistent with hypotheses that calcium appetite is mediated by circulating calcium, PTH and CT infusions produced reciprocal changes in plasma calcium concentrations and CaCl2 intake. However, the finding that 1,25(OH)2D elevated both plasma calcium concentrations and CaCl2 intake raises the possibility that one or more of the hormones may mediate calcium appetite directly.

Effect of Norepinephrine on Fetal Breathing in Sheep

We tested the hypothesis that the surge of norepinephrine at birth is associated with the establishment of continuous breathing. Therefore, we studied whether the administration of norepinephrine could enhance fetal breathing during administration of oxygen, or 100% O₂ plus cord occlusion, and if phenoxybenzamine would reverse these changes. Fetal sheep were instrumented in late gestation to measure electrocortical activity and diaphragmatic electromyography. These parameters and blood gases were measured before and during in utero administration of nitrogen, 100% O₂, 100% O₂ plus umbilical cord occlusion, and subsequently during umbilical reperfusion and recovery. Nine fetuses (14 experiments) received continuous norepinephrine (0.13 µg/kg/min) throughout the experiment while 9 other fetuses (18 experiments) underwent the same treatment without the hormonal infusion. We found that norepinephrine inhibited the breathing induced by 100% O₂ plus cord occlusion, despite a significant increase in the duration of low-voltage electrocortical activity; phenoxybenzamine reverted these changes. The findings suggest that the surge of norepinephrine at birth is probably not the primary mechanism for establishment of continuous breathing.

Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo.

The effect of in vivo infusion of the peptide hormone glucagon-like peptide 2 (GLP-2) on glucose transport across the rat jejunal brush-border membrane (BBM) was assessed using isolated membrane vesicles. A 2-h infusion of GLP-2 produced a marked acceleration of sodium-dependent glucose uptake into BBM vesicles with a significant overshoot. There was no change in vesicle space or permeability resulting from the hormone infusion. Kinetic analysis showed this stimulation to be the result of a three-fold increase in the maximal rate of transport, with no consistent change in the affinity constant (Km). The time course of this response showed that the effect was observable, but smaller, after only 30 min of hormone infusion and was maximal after 1 h. Sodium-dependent phloridzin binding to the membrane vesicles showed a parallel increase in maximal binding after 1 and 2 h of hormone infusion. Western blotting showed a similar increase in sodium-dependent glucose transporter 1 (SGLT-1) abundance. The effect of GLP-2 could be blocked by luminal brefeldin A or wortmannin. These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response.

Zinc deficiency inhibits the direct growth effect of growth hormone on the tibia of hypophysectomized rats.

The effect of zinc deficiency on the direct-growth effect of growth hormone (GH) on tibia growth in hypophysectomized rats was studied. There were three dietary groups. Zinc deficient (ZD) group (0.9 mg/kg diet), control (C) group (66 mg/kg diet) and zinc adequate pair fed (PF) group (66 mg zinc/kg diet). All rats in each group received local infusion of recombinant human-growth hormone (hGH) (1 microgram/d), except for half of the animals in the control group, which were sham-treated, receiving vehicle infusion only. The substances were infused continuously for 13 d by osmotic minipumps through a catheter implanted into the right femoral artery. Food intake was lower and body weight loss was greater in ZD, and PF animals compared with C animals (p < 0.001). Tissue-zinc concentration and plasma alkaline-phosphatase activity were decreased (p < 0.05) by dietary-zinc deficiency. GH infusion increased the tibial-epiphyseal width of the treated right limb, but not of the noninfused left limb in C and PF animals. However, in ZD rats, no difference was found between the infused and the noninfused limbs. These results demonstrate that zinc deficiency inhibits the direct-growth effect of GH on long-bone growth.

Somatostatin attenuates the hyperthermia induced increase in neutrophil concentration

This study was designed to test the hypothesis that the immune changes seen during in vivo whole body hyperthermia are mediated by elevations in the plasma concentrations of either catecholamines, growth hormone or beta-endorphins. Eight healthy volunteers were immersed in a hot water bath (WI; water temperature 39.5 degrees C) for 2 h during which their rectal temperature rose to 39.5 degrees C. In a single blind, randomized, cross-over study the stress hormone effects were blocked one at a time by administration of propranolol, somatostatin or naloxone; the results were compared to those obtained during saline infusion (control). Blood samples were collected before, at the end of 2 h of WI (body temperature 39.5 degrees C), and 2 h later. Hormone blockade did not abolish the hyperthermia-induced recruitment of natural killer (NK) cells to the blood, and no influence was observed on the percentages or concentrations of any other subpopulations of blood mononuclear cells, except that the number of cluster designation (CD)3+ cells slightly increased after hyperthermia only in the propranolol experiment. Furthermore, the NK cell activity, both unstimulated and interferon-alpha or interleukin-2 stimulated, did not differ from the control situation. It is of interest, however, that somatostatin partly abolished the hyperthermia induced increase in the neutrophil number. Based on these data and previous results showing that growth hormone infusion increases the concentration of neutrophils in the blood, it is suggested that growth hormone is at least partly responsible for hyperthermia induced neutrocytosis.

Effect of age on the response to parathyroid hormone

Serum phosphate (PO 4) levels and the tubular threshold for PO 4 corrected for glomerular filtration (TP/GF) are age-dependent, being higher in children than in adults. We evaluated the effect of age on the response to infusion of parathyroid hormone (1–34) (PTH) in healthy children (n = 8) and adults (n = 12). In addition, six patients with pseudohypoparathyroidism (PHP) and two with PTH deficiency (hypoparathyroidism [HP]) were also studied. At baseline, TP/GF in normal subjects was inversely correlated with urinary cyclic adenosine monophosphate corrected for glomerular filtration (UcAMP/GF) ( P < .0359). After PTH administration in the controls, UcAMP/GF was inversely correlated with TP/GF ( P < .0007) and directly correlated with maximal fractional extraction of PO 4 (FEP) ( P < .0002). The slope of the regression of TP/GF ( P < .0076) and FEP ( P < .0034) with UcAMP/GF was steeper in children than in adults. Two HP patients had high PTH-stimulated UcAMP/GF levels, but stimulated TP/GF and FEP were not changed commensurate with levels that would expected from the normative data. In six patients with PHP, PTH-stimulated TP/GF was also correlated with peak UcAMP/GF ( r = .96, P < .002). PHP patients could be distinguished from normal controls based on the combination of low peak FEP or high TP/GF together with low peak UcAMP/GF. Thus, in normal subjects, the phosphaturic response to PTH is correlated with the increase in urinary cAMP and is age-dependent, with a greater decrease of TP/GF in children than in adults.

Physiological inactivation of vasoactive hormones in rainbow trout

Hormone titers are affected by interplay between secretion and inactivation processes. While secretion is a focal process, inactivation mechanisms are often complex and poorly understood. In the present study, inactivation of cardiovascular regulatory hormones was examined from a physiological perspective by analyzing the half-time (t½) for recovery of dorsal and ventral aortic and central venous pressure, cardiac output, heart rate, and systemic and branchial vascular resistance following infusion or injection of hormones into conscious rainbow trout, Oncorhynchus mykiss. When possible, these were compared to recovery t½ of isolated vessel rings in vitro. The t½ for epinephrine or norepinephrine recovery in vivo was 3–4 min, approximately twice as long as recovery t½ for isolated celiacomesenteric and epibranchial artery rings in vitro. Thus, the rate-limiting step in vascular relaxation is the concentration of circulating catecholamine concentrations, and not metabolic or mechanical events within the vascular wall. The in vivo recovery t½ following angiotensin II (ANG II) infusion was 6–7 min, nearly twice that of catecholamines, but also greater than the t½ following bolus ANG II injection, inhibition of angiotensin converting enzyme with captopril or injection of trout bradykinin. Arginine vasotocin (AVT) recovery t½ in vivo, was considerably longer (20–30 min) than either catecholamine or ANG II t½ and longer than AVT recovery t½ of isolated vessels in vitro (5–6 min). The inactivation kinetics of catecholamines are consistent with circulatory convection-limited processes and do not appear to be limited by either tissue uptake or enzymatic degradation. This is probably the fastest type of ‘on-off’ endocrine regulation in fish. Inactivation of ANG II and bradykinin are also convection limited, but ANG II metabolism may become saturated with high doses of exogenous ANG II. AVT inactivation is not convection limited and may compensate for a quantitatively lower capacity of the pituitary for peptide secretion, or less emphasis on AVT as an on/off effector of vascular resistance. J. Exp. Zool. 279:254–264, 1997. © 1997 Wiley-Liss, Inc.

Lipoproteins and cardiovascular reactivity.

The observation that relatively short periods of cholesterol lowering therapy can reduce the incidence of coronary artery disease events has prompted interest in the short term effects of lipoproteins on cardiovascular responsiveness. Numerous studies in animals and humans have demonstrated that oxidized LDL-cholesterol can impair endothelial dependent vasodilation in coronary arteries and peripheral resistance vessels. Reduction of plasma LDL-cholesterol levels in hypercholesterolaemic patients improves nitric oxide mediated vasodilator responses in the coronary and peripheral circulation. LDL-cholesterol also potentiates responses to vasoconstrictors such as noradrenaline and endothelin-1 in the absence of endothelium, possibly by enhancing calcium influx into vascular smooth muscle cells. Pharmacological reduction of plasma LDL-cholesterol levels has been shown to reduce blood pressure responses to intravenous infusions of pressor hormones and to stress. However, the relative contribution of changes in endothelial dependent vasodilation and vasoconstrictor or inotropic responses remains to be established. Short term changes in LDL-cholesterol produce changes in cardiovascular responsiveness that may influence the development of ischaemic events.

Movement-related cortical potentials and contingent negative variation in olivopontocerebellar atrophy.

Movement-related cortical potentials (MRCPs) and contingent negative variation (CNV) were recorded in 8 cases of olivopontocerebellar atrophy (OPCA) and 8 age-matched healthy controls. The amplitude of the negative slope (NS') was smaller in the OPCA group than in the healthy control group. The amplitude of late CNV was smaller in OPCA group than in the healthy control group. These abnormalities in MRCPs and CNV were improved by intravenous infusion of thyrotropin releasing hormone.

Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog.

The role of epinephrine and norepinephrine in contributing to the alterations in hepatic glucose metabolism during a 70-h stress hormone infusion (SHI) was investigated in four groups of chronically catheterized (20-h-fasted) conscious dogs. SHI increased glucagon (approximately 5-fold), epinephrine (approximately 10-fold), norepinephrine (approximately 10-fold), and cortisol (approximately 6-fold) levels. Dogs received either all the hormones (SHI; n = 5), all the hormones except epinephrine (SHI-Epi; n = 6), or all the hormones except norepinephrine (SHI-NE; n = 6). In addition, six dogs received saline only (Sal). Glucose production (Ra) and gluconeogenesis were assessed after a 70-h hormone or saline infusion with the use of tracer ([3-(3)H]glucose and [U-(14)C]alanine) and arteriovenous difference techniques. SHI increased glucose levels (108 +/- 2 vs. 189 +/- 10 mg/dl) and Ra (2.6 +/- 0.2 vs. 4.1 +/- 0.3 mg x kg(-1) x min(-1)) compared with Sal. The absence of an increase in epinephrine markedly attenuated these changes (glucose and Ra were 140 +/- 6 mg/dl and 2.7 +/- 0.4 mg x kg(-1) x min(-1), respectively). Only 25% of the blunted rise in Ra could be accounted for by an attenuation of the rise in net hepatic gluconeogenic precursor uptake (0.9 +/- 0.1, 1.5 +/- 0.1, and 1.1 +/- 0.2 mg x kg(-1) x min(-1) for Sal, SHI, and SHI-Epi, respectively). The absence of an increase in norepinephrine did not blunt the rise in arterial glucose levels, Ra, or net hepatic gluconeogenic precursor uptake (they rose to 195 +/- 21 mg/dl, 3.7 +/- 0.5 mg x kg(-1) x min(-1), and 1.7 +/- 0.2 mg x kg(-1) min(-1), respectively). In summary, during chronic SHI, the rise in epinephrine exerts potent stimulatory effects on glucose production principally by enhancing hepatic glycogenolysis, although the rise in circulating norepinephrine has minimal effects.

Antisense oligonucleotides in neuroendocrinology: Enthusiasm and frustration

Antisense oligodeoxynucleotides (ODN) offer the potential advantage to manipulate neuropeptide or neuropeptide receptor expression within the brain transiently and site-specifically, thus providing a tool for neuroendocrinological research into the physiological function of a particular neuropeptide system. In this study, various approaches are introduced which reveal that antisense ODN may exert acute, short-term effects on neuronal responsiveness to afferent stimuli, as well as long-term effects on neuropeptide/receptor protein availability in a given system depending on the duration of treatment. Short-term effects were seen in that oxytocin (OXT) and vasopressin (AVP) antisense ODN affected electrophysiological and secretory parameters of oxytocinergic and vasopressinergic neurons, respectively, as well as their ability to express the Fos protein in response to afferent stimulation a few hours after a single infusion into the hypothalamic supraoptic nucleus. In this study, two methodological approaches to study long-term effects of the antisense ODN are exemplified, in which antisense ODN directed against the mRNA coding for the neuropeptide itself or its receptor were used. The repeated infusion of corticotropin releasing hormone (CRH) antisense ODN into the paraventricular nucleus resulted in reduced immunoreactive CRH, but not AVP, in the external zone of the median eminence. Furthermore, in order to evaluate the receptor-mediated effects of CRH and AVP released locally within the paraventricular nucleus on adrenocorticotropin (ACTH) release from the pituitary, CRH receptor (and also AVP receptor) antisense ODN were repeatedly infused into the hypothalamic nuclei; this treatment resulted in an elevation of stimulated, but not basal, ACTH release into the blood. However, in addition to these obvious antisense effects, results are discussed which demonstrate sequence-unspecific effects of phosphorothioated ODN, suggesting that some of their mechanisms of action are not yet understood.

Adrenocorticotropic hormone infusion as a novel treatment for postdural puncture headache

In two patients, one scheduled for epidural anesthesia and the other for placement of a spinal catheter for operative procedures, severe postdural puncture headache developed and was refractory to conservative therapy. The first patient had several unintentional dural punctures, and the second underwent a planned dural puncture with an 18-gauge needle for insertion of a 20-gauge catheter. When neither patient responded to conservative therapy following development of postdural puncture headache, an infusion of adrenocorticotropic hormone (ACTH) was given prior to consideration of epidural blood patching. Both patients obtained complete and permanent relief from their headaches. A single treatment with ACTH may offer an alternative therapy in the treatment of postdural puncture headache.

Dysregulation of calcium homeostasis after severe burn injury in children: Possible role of magnesium depletion

Objective: To determine the cause and extent of hypocalcemia observed in children after severe burns. Design: We studied 10 children with burns covering 57% ± 17% (SD) body surface area, ages 9.6 ± 4.7 years, who were admitted consecutively during a 6-month period. Diet supplied a minimum of 2.7 gm/m 2 of calcium, 0.3 gm/m 2 of magnesium, and 2.2 gm/m 2 phosphate. Blood specimens were obtained daily for 10 ± 5 days for the following tests: (1) simultaneous analysis for ionized calcium, magnesium, and intact parathyroid hormone (group A); (2) two of these children, randomly selected, had serial 2-hour determinations on a single day (group B); (3) a modified Ellsworth-Howard test, consisting of a 10-minute infusion of synthetic parathyroid hormone 18 ± 10 days postburn and associated changes in urinary cyclic adenosine monophosphate excretion and renal threshold phosphate concentration (group C). Three of these children, when normomagnesemic, also received a standard magnesium infusion to determine magnesium retention (group D). Data were analyzed with chi-square, regression analysis, and nonparametric testing as appropriate. Results: All patients showed sustained hypocalcemia and hypomagnesemia; intact parathyroid hormone response was inappropriately low and response to synthetic parathyroid hormone infusion was blunted. Lowest ionized calcium levels were associated with hypomagnesemia. Conclusion: Hypoparathyroidism and blunted renal response to parathyroid hormone suggest that magnesium depletion may contribute to their pathogenesis. Magnesium repletion and monitoring are recommended. (J Pediatr 1997;131:246-51)

Concomitant infusion of ovine corticotropin-releasing hormone does not prevent suppression of the hypothalamus-pituitary-adrenal axis by dexamethasone in male rats.

Glucocorticoids (GCs) suppress the hypothalamus-pituitary-adrenal (HPA) axis at various sites including hypothalamus, pituitary and extrahypothalamic brain. Previous studies have shown that corticotropin-releasing hormone (CRH) and vasopressin facilitate the recovery of HPA axis suppressed by GCs. In this study, we investigate whether the concomitant continuous infusion of CRH may prevent the suppression of HPA axis by GCs. Groups of male Wistar rats weighing 140 to 160 g were implanted subcutaneously with Alzet osmotic pump for delivery of dexamethasone (DEX), 2 micrograms/h and/or CRH, 0.66 microgram/h. Control rats were implanted with sialistic tube of similar size. Rats were decapitated 3 or 7 days after osmotic pump implantation. In spite of the suppression of plasma corticosterone, the body weight (BW), adrenal weight (AW), plasma corticotropin (ACTH) and pituitary ACTH content of rats treated with DEX for 3 days were not significantly different from those of control rats. Concomitant infusion of ovine CRH (oCRH) and DEX for 3 days caused impaired BW gain, adrenal atrophy in addition to further reduction of plasma corticosterone. Treatment with DEX and/or oCRH for 7 days caused further suppression of HPA axis as shown by reduced pituitary ACTH content. In conclusion, simultaneous infusion of oCRH and DEX does not prevent and may even worsen HPA axis suppression by DEX.

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

Differential Sex Steroid Negative Feedback Regulation of Pulsatile Follicle-Stimulating Hormone Secretion in Healthy Older Men: Deconvolution Analysis and Steady- State Sex-Steroid Hormone Infusions in Frequently Sampled Healthy Older Individuals

Differential Sex Steroid Negative Feedback Regulation of Pulsatile Follicle-Stimulating Hormone Secretion in Healthy Older Men: Deconvolution Analysis and Steady- State Sex-Steroid Hormone Infusions in Frequently Sampled Healthy Older Individuals

The Short-Term Infusion of Ovine Corticotropin-Releasing Hormone Does Not Alter Luteinizing Hormone Concentrations in Young Adult Men

The Short-Term Infusion of Ovine Corticotropin-Releasing Hormone Does Not Alter Luteinizing Hormone Concentrations in Young Adult Men

Implications of Immediate-Early Gene Induction in the Brain Following Sexual Stimulation of Female and Male Rodents

Induction of immediate-early genes (IEGs), such as c-fos, has been widely used to mark the activation of brain regions following different types of sexual stimulation and behavior. A relatively common set of hormone-concentrating basal forebrain and midbrain structures in female and male rodents is activated by copulatory stimulation, in particular, stimulation of sensory nerves that innervate the penis or vagina/cervix, olfactory or pheremonal stimuli, and conditioned sexual incentives. These regions include the preoptic area, lateral septum, bed nucleus of the stria terminalis, paraventricular hypothalamus, ventromedial hypothalamus, medial amygdala, ventral premammillary nuclei, ventral tegmentum, central tegmental field, mesencephalic central gray, and peripeduncular nuclei. Regions that do not contain classic intracellular steroid receptors, such as the ventral and dorsal striatum or cortex, are also activated. IEGs have also been colocalized with cytoplasmic proteins like GnRH and oxytocin, and have been used in conjunction with retrograde tracers to reveal functional pathways associated with different sexual behaviors. Steroid hormones can also alter the ability of sexual stimulation to induce IEGs. Despite the many similarities, some differences in IEG induction between sexes have also been found. We review these findings and raise the question of what IEG induction in the brain actually means for sexual behavior, that is, whether it indicates the perception of sexual stimulation, commands for motor output, or the stimulation of a future behavioral or neuroendocrine event related to the consequences of sexual stimulation. To understand the role of a particular activated region, the behavioral or neuroendocrine effects of lesions, electrical stimulation, drug or hormone infusions, must also be known.

P300 And cerebral blood flow before and after trh in olivopontocerebellar atrophy

Ten cases of olivopontocerebellar atrophy (OPCA) (mean age 56 × 9 years) and 8 healthy controls (mean age 58 × 9 years) were studied. The P300 was measured with a Synax 1100 evoked potential recorder and the regional cerebral blood flow was measured using the stable xenon computed tomography method. The P300 latency was significantly longer in the OPCA group than in the healthy control group. The P300 latency after the intravenous infusion of thyrotropin releasing hormone (TRH) in the OPCA group was significantly shorter than that before the intravenous infusion of TRH. The blood flows in all the measured areas (the cerebellar cortex, the cerebellar white matter, the brainstem, the thalamus, the basal ganglia, the frontal lobe cortex and the frontal lobe white matter) were significantly lower in the OPCA group than in the healthy control group. The blood flows in the cerebellar cortex and in the frontal lobe cortex after the intravenous infusion of TRH were significantly higher than those before the intravenous infusion of TRH. The prolongation of P300 latency in the OPCA group suggests that subclinical disturbance in recognition function is present in OPCA and may be related to the blood flow decrease outside the cerebellum.

Osteopetrosis

Congenital osteopetrosis is a group of disorders resulting in decreased osteoclastic function and hence decreased bone resorption. Various medical treatments have been attempted to ameliorate the osteopetrotic condition. A calcium-deficient diet has limited further sclerosis in some patients. Prednisone therapy has improved haematological function in some patients, but has not resulted in a reduction in bone mass. Calcitrophic hormones, such as parathyroid hormone (PTH) infusions and oral calcitriol, stimulate osteoclastic activity, and calcitriol in particular has stimulated osteoclastic bone resorption in some patients with osteopetrosis. Bone marrow transplantation, although curative, is limited by paucity of donors, risk of graft-versus-host disease and relapse of the disease. The demonstration of defective leucocyte superoxide production in osteopetrotic patients and the premise that osteoclasts appear to arise from the granulocyte macrophage lineage have led to attempts at treating osteopetrosis with immunomodulators. Since treatment with recombinant interferon-γ-1b (interferon γ-1b, IFNγ-1b) has resulted in increased level of superoxide generation and clinical improvement in chronic granulomatous disease, a similar strategy has been employed using IFNγ-1b to treat patients with osteopetrosis. IFNγ-1b has been demonstrated to increase osteoclastic bone resorption and leucocytic function. Long term therapy with IFNγ-1b by subcutaneous injection 3 times weekly resulted in marked clinical improvement, a decreased incidence of infections, a decreased trabecular bone mass, and an increased marrow space resulting in improved haemopoiesis. The therapy has been associated with few adverse effects, mainly fever and diarrhoea which have been managed with a reduction in IFNγ-1b dosage. The low-calcium diet occasionally results in hypocalcaemic tetany, which may be corrected by increased dietary calcium intake. Thus, IFNγ-1b has a distinct place in the therapeutic armamentarium for patients with osteopetrosis and is a feasible treatment option in such patients.