Role of food intake in the modulation of hexarelin-induced growth hormone release in normal human subjects.

Hexarelin (HEX) is a new synthetic analog of the Growth Hormone releasing peptides and is stronger than GHRH in releasing GH in vivo. No information is available on the effect of food ingestion on HEX-induced GH secretion. On the other hand, we have previously demonstrated that food intake at lunchtime in normal subjects has an inhibitory effect on the GH response to GHRH. The aim of the present study was to investigate the effect of food ingestion on GH secretion induced by HEX as compared to GHRH in six normal men (aged 23-29 years) and six normal women (aged 24-29 years). The body weights for all subjects were within 120% of their ideal body weight, according to their sex and age. Our data confirm that HEX is much more powerful than GHRH in inducing GH release in humans, both in the fasting state (GH-AUC: 3010 +/- 695 after HEX, vs. 1339 +/- 281 after GHRH, microg/L/120 min; p<0.06) and after a meal (GH-AUC: 1523 +/- 121, after HEX, vs. 309 +/- 61, after GHRH, microg/L/120 min; p<0.06). Moreover, our study shows that food intake partially blunts the fasting GH response to HEX (GH-AUC: 3010 +/- 695 after HEX, in fasting state, vs. 1523 +/- 121 after HEX, after meal, microg/L/120 min; p<0.06; mean inhibition of AUC 41.02 +/- 7.96%), whereas it nearly abolishes the GH response to GHRH in the same subjects (GH-AUC: 1339 +/- 281 after GHRH, in fasting state, vs. 309 +/- 61 after GHRH, after meal, microg/L/120 min; p<0.06; mean inhibition of AUC 70.31 +/- 6.22%). In conclusion, our study confirms that HEX acts differently from GHRH; the GH releasing effect of HEX could be only partially influenced by the physiological metabolic or neuroendocrine food-related modifications.     

Age-, cycle- and topographic dependency of human myometrial prostaglandin (6-keto-PGF1 alpha, PGF2 alpha)-synthesis in vitro

Specimens of human myometrium (isthmus and fundus) freshly obtained at hysterectomy were immediately transferred in ice cold Tyrode solution and placed in superfusion chambers. Spontaneous contractions were recorded, the effluent of the myometrium was analyzed for PGF2 alpha and 6-keto-PGF1 alpha by use of specific radioimmunoassay systems. Dating of the menstrual cycle was achieved by histological evaluation of the endometrium. The PG release rates expressed as ng/min/g wet weight were correlated to the patients age and to the phase of the menstrual cycle. The production rates of 6-keto-PGF1 alpha were negatively correlated to the age of the patients and declined in fundus specimens from 2.89 +/- 0.35 ng/min/g wet weight in 39-42 years old patients to 0.52 +/- 0.17 ng/min/g wet weight in 48-52 years old women during the secretory phase (p less than 0.001). Similar significant correlations were found in specimens obtained from the isthmus uteri. During the proliferative phase fundus specimens produced on average 1.61 +/- 0.67 ng/min/g wet weight in 39-42 years old patients and 0.49 +/- 0.12 ng/min/g wet weight 6-keto-PGF1 alpha in 48-52 years old women respectively (p les than 0.001). The PGF2 alpha synthesis in myometrial specimens of fundus or isthmus origin was significantly lower than 6-keto-PGF1 alpha and did not correlate to the age of the patients during the proliferative phase. However, PGF2 alpha release rates during the secretory phase were significantly (p less than 0.001) higher in younger women. These results suggest an age-, cycle- and topographic dependency of PGI2 synthesis in human myometrial tissue.     

An application of nanoindentation technique to measure bone tissue Lamellae properties

Measuring the microscopic mechanical properties of bone tissue is important in support of understanding the etiology and pathogenesis of many bone diseases. Knowledge about these properties provides a context for estimating the local mechanical environment of bone related cells thait coordinate the adaptation to loads experienced at the whole organ level. The objective of this study was to determine the effects of experimental testing parameters on nanoindentation measures of lamellar-level bone mechanical properties. Specifically, we examined the effect of specimen preparation condition, indentation depth, repetitive loading, time delay, and displacement rate. The nanoindentation experiments produced measures of lamellar elastic moduli for human cortical bone (average value of 17.7 +/- 4.0 GPa for osteons and 19.3 +/- 4.7 GPa for interstitial bone tissue). In addition, the hardness measurements produced results consistent with data in the literature (average 0.52 +/- 0.15 GPa for osteons and 0.59 +/- 0.20 GPa for interstitial bone tissue). Consistent modulus values can be obtained from a 500-nm-deep indent. The results also indicated that the moduli and hardnesses of the dry specimens are significantly greater (22.6% and 56.9%, respectively) than those of the wet and wet and embedded specimens. The latter two groups were not different. The moduli obtained at a 5-nm/s loading rate were significantly lower than the values at the 10- and 20-nm/s loading rates while the 10- and 20-nm/s rates were not significantly different. The hardness measurements showed similar rate-dependent results. The preliminary results indicated that interstitial bone tissue has significantly higher modulus and hardness than osteonal bone tissue. In addition, a significant correlation between hardness and elastic modulus was observed.     

K(+)-p-nitrophenylphosphatase activity in rat brain and liver

K(+)-p-nitrophenylphosphatase (K(+)pNPPase) is the enzyme, which is considered to be involved in K(+)-dependent hydrolysis of the phosphoenzyme in the reaction cycle of Na(+), K(+)ATPase. The aim of our present study was to characterize some features of K(+)pNPPase in homogenates of the rat brain and liver. We determined p-nitrophenylphosphatase (pNPPase) activity in the presence of various ion combinations (Mg(2+)+ K(+), Mg(2+), K(+)). We found a higher total pNPPase activity in the brain (0.8+/-0.079 nkat/mg protein) than in the liver (0.08+/-0.01 nkat/mg protein). Contrary to the liver, the main part of the total brain activity was K(+)-dependent. The activity of K(+)pNPPase was significantly higher in cerebral cortex homogenates (0.86+/-0.073 nkat/mg protein) in comparison to those of the whole brain (0.57+/-0.075 nkat/mg protein). The specific K(+)pNPPase activity was two times higher in the isolated pellet fraction (0.911+/-0.07 nkat/mg protein), rich in synaptosomes, compared to the whole brain homogenate (0.57+/-0.075 nkat/mg protein). Our results demonstrate the high activity of K(+)pNPPase in the brain tissue and its distribution mainly into the pellet fraction, what might indicate a possible role of K(+)pNPPase in specific structures of the brain, e.g. in synaptosomes.     

Immunocytochemical and biochemical identification of angiotensin II in human nasal tissue

Angiotensin II (ANG II) was identified immunocytochemically and biochemically in biopsy samples of human nasal tissue. Staining for ANG II was predominantly found in structures similar to a string of pearls with consecutive short varicose areas, which is characteristic for neuronal tissue. The localization of ANG II in neurons was confirmed by positive staining of adjacent tissue sections with a specific antibody to neurofilament or doublestaining with both antibodies in one section. Likewise, ANG II-like material was also determined radioimmunologically in nasal tissue extracts. The concentrations of ANG II varied form 1.28 to 332.78 fmol/g wet tissue weight with an average concentration of 79.61+/-44.09 fmol ANG II/g wet tissue weight (mean+/-SEM, n=7). The ANG II-immunoreactive material was further characterized biochemically by HPLC on a reversed phase C(18) column in an acetonitrile and methanol gradient as Ile(5)-ANG II and ANG II metabolites such as Ile(4)-ANG III, Ile(3)-ANG II(3-8)hexapeptide and Ile(2)-ANG II(4-8)pentapeptide.     

Bone resorption in osteosclerotic mice is reduced in vitro

Osteopetrosis in mammals results from a congenital reduction in bone resorption. Calvarial organ cultures were used to measure bone resorption in osteosclerotic (oc/oc) mice and their normal littermates. Measurements of cell-mediated resorption indicate that baseline isotope release by mutant calvariae was only 57% of that observed in normal littermates and isotope release by mutant bone in the presence of parathyroid hormone (PTH) was only 60% of that in normal controls. However, the response of oc calvariae to PTH was not different from normal bone when considered with respect to baseline resorption. These data indicate that bone resorption in oc mice is reduced in both its basal level and in response to PTH and suggest that oc mice are unable to establish normal baseline resorption which may in turn compromise their responsiveness to PTH.     

Potentialities of temporal bone CT in the diagnosis of chronic purulent otitis media and its complications

Temporal bone CT was used to examine a group of 87 patients with chronic purulent otitis media (103 temporal bones). The patients' age ranged from 2 to 74 years. A scheme was developed and proposed to evaluate the temporal bone by CT. The CT signs of chronic purulent otitis media uncomplicated by cholesteatoma and those of cholesteatomic purulent otitis were identified. The CT symptomatology of chronic purulent otitis includes: sclerotic changes in the bone tissue of the mastoid process, impaired pneumatization of the cavities of the middle ear, including the tympanic cavity, destructive changes in auditory ossicles, carious changes in the walls of the cavities of the middle ear. The CT semiotics of cholesteatoma depends on its site and spread into the temporal bone and includes as follows: deformation of the epitympanum due to soft tissue mass-induced destruction of the lateral wall; the dilated entrance into the antrum; the presence of a cavity with the sclerosed walls in the antromastoid area; carious changes in the auditory ossicles; the displacement of a chain of ossicles medially or laterally in relation to the initial site of cholesteatoma. CT reflects carious changes in the walls of the cavities of the middle ear, including the roof and labyrinthine wall of the tympanum, which allows labyrinthine fistula and intracranial cholesteatomic complications. The study of the temporal bone by the proposed scheme may reveal anomalies and the specific features of its structure: the presentation of the sigmoid sinus, the high elevation of the bulb of the jugular vein, diverticulum of the latter, the low standing of the bottom of the ACH.     

Effect of bromocriptine on prostacyclin release and cyclic nucleotides on rat aortic and uterine tissues

The effect of bromocriptine mesylate on cyclic nucleotides and PGI2 release by rat aortic and uterine tissues was investigated. Treatment of rats with bromocriptine (10 mg kg-1 I.P. daily for 14 days) increased PGI2 release by the thoracic aorta from 0.67 +/- 0.02 to 1.4 +/- 0.03 ng/mg wet tissue (P less than 0.001; n = 6). This increase was antagonized by treatment with sulpiride (15 mg kg-l). Incubation of the arterial tissue with bromocriptine (50 micrograms ml-1) in vitro also stimulated PGI2 release. Mepacrine (160 micrograms ml-1) significantly decreased both basal and stimulated PGI2 release. Incubation of myometrial tissue from pregnant rats with bromocriptine (50 micrograms ml-1) in vitro significantly decreased PGI2 release from 1.25 +/- 0.07 to 0.60 +/- 0.08 ng/mg wet tissue (P less than 0.05, n = 6). It also elevated uterine cAMP from 40 +/- 2 to 64 +/- 3 pmoles/100 mg wet tissue. Both effects were antagonized by sulpiride. Bromocriptine did not affect uterine cGMP or the cyclic nucleotides in the aorta. It is concluded that the increase in aortic PGI2 was mediated via activation of dopamine D-2 receptors that stimulate phospholipase A2 enzyme. The decrease in myometrial PGI2 release may be related to the increase in uterine cAMP resulting from activation of dopamine D-1 receptors. Previous studies suggested a role for PGI2 in implantation in the rat. The results suggest that the inhibitory effect on uterine PGI2 may underlie the reported inhibition of bromocriptine on implantation. On broad basis, the decrease in uterine PGI2 together with the reported luteolytic effect of bromocriptine point to a potential role for the compound in postcoital contraception.     

Effects of solution of low pH and taurocholate on release of beta-endorphin-like immunoreactivity from human duodenal mucosa in vitro

The presence of beta-endorphin-like immunoreactivity (beta-EpLI) in human duodenum and its release were studied. beta-EpLI was detected in the duodenum (mucosa, 26.7 +/- 6.3 pmol/g wet weight, mean +/- SEM; remaining tissue 23.1 +/- 5.3 pmol/g wet weight) and the stomach (7.1 pmol/g wet weight). The two activities gave similar curves for inhibition of beta-Ep radioimmunoassay of synthetic beta-Ep. On gel-filtration chromatography of a duodenal extract, two components of beta-EpLI were separated. When human duodenal mucosa was perfused with a solution of pH2 or 1mM or 5mM taurocholate, the release of beta-EpLI from mucosa into the perfusate increased 2-4 fold. These results indicate that beta-EpLI present in human duodenal is released by the direct action of low pH or taurocholate on the duodenal mucosa and suggest that it may have a physiological role.     

Urease activity of adherent bacteria in the sheep rumen

In experiments on six sheep fed on a low protein diet (6.2 g N/day), it was found that the urease activity of the rumen fluid did not change significantly in the first 6 hours after feeding and that it ranged from 45 to 75 nkat.ml-1. The major portion was bound to the bacterial fraction and formed about 70% of total rumen fluid activity. Urease activity determined in food particles with adherent bacteria removed from the rumen before and 3 and 6 hours after feeding ranged from 20 to 26 nkat.g-1 food (wet weight), and on rumen wall samples with adherent bacteria from 30 to 800 nkat per 2.5 cm2 tissue. Again, no significant changes correlated to the time after feeding were found. The results show that urease activity in the sheep rumen is localized on food particles and on rumen wall epithelium with adherent bacteria, as well as in the rumen fluid.     

Insulin and glucagon in rats with islet cell tumors induced by small doses of streptozotocin

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 +/- 8.60 and 35.07 +/- 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 +/- 0.61 and 2.24 +/- 0.67 micrograms/g wet weight, respectively). These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.     

Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (V(max)) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr; FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC is forced vital capacity; means +/- SE) and nine healthy age-matched controls (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD patients displayed lower (P < 0.05) V(max) (mol.kg protein(-1).h(-1)) for cytochrome c oxidase (COX; 21.2 +/- 2.0 vs. 28.7 +/- 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 +/- 0.14 vs. 3.74 +/- 0.12) but not citrate synthase (CS; 2.20 +/- 0.16 vs. 3.19 +/- 0.5). While no differences between groups were observed in V(max) for creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to beta-oxidation.     

Weight-bearing exercise and markers of bone turnover in female athletes.

Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.     

n-acetyl-beta-hexosaminidase activity in human breast milk

1. The lysosomal enzyme, N-acetyl-beta-hexosaminidase (HEX) is present in human breast milk. It is composed predominantly of "A" (heat-labile) and "B" (heat-stable) isozymes which coelute with the corresponding major serum isozymes on DE-52 ion-exchange chromatography. 2. Total HEX activity in "early" milk obtained at 2.8 +/- 1.4 weeks post partum, is approx. 2.5-fold higher (87 +/- 29 nmol/60'/mg protein. n = 10) than that of pregnancy serum (35.7 nmol/60'/mg protein) prior to delivery. 3. These levels increase to greater than 3-fold (110 +/- 20 nmol/60'/mg protein, n = 13) as the milk matures (10.3 +/- 4.2 weeks). 4. The specific activity of HEX A in the milk changes little with time post partum, because absolute 5. In contrast, HEX B specific activity is increased, as absolute levels (per volume) remain constant in the face of decreasing milk protein content, 5. These changes result in a high degree of correlation (r = 0.81) between time of lactation and % HEX A observed.     

The influence of dietary sodium on bone development in growing rats

The present study investigated the effects of dietary sodium on bone growth in young rats. Five-week-old rats were fed one of three different diets for 60 days: low sodium (NaCl, 0.32 g/kg diet), normal sodium (NaCl, 2.6 g/kg) and high sodium (NaCl, 20 g/kg). The proximal tibial metaphysis (PTM), the fifth lumbar vertebra (LV5) and the middle part of the tibia shaft (TX) were analysed by bone histomorphometry. The expression of three osteogenesis genes, Runx2, osteopontin and osteocalcin, was determined by RT-PCR in bone samples from the skull. In both the PTM and LV5, trabecular area and thickness were increased by the low-sodium diet, while the high-sodium diet decreased trabecular area in LV5. Dynamic data revealed that sodium restriction increased bone formation parameters in the PTM and LV5, but decreased bone resorption in LV5. In TX, endosteal bone formation was enhanced by the low-sodium diet and depressed by the high-sodium diet compared to the normal sodium group. But there were no statistically changes in the cortical bone area of TX. Low-sodium intake significantly enhanced the expression of all three osteogenesis genes compared to the normal sodium group, while high-sodium intake suppressed osteogenic gene expression. Our results suggest that sodium restriction in growing rats promotes bone development by influencing both bone formation and resorption.     

Hypertrophic scar: an interruption in the remodeling of repair--a laser Doppler blood flow study.

Soft-tissue dermal loss does not regenerate; instead, it is replaced with scar. The extent of scarring is directly related to the severity of tissue loss (in terms of volume and depth). Commonly, an acute dermal loss will heal with excessive scar, hypertrophic scar. A hypertrophic scar is elevated but is contained within the boundaries of the initial injury. Hypertrophic scars have a reddish appearance, indicating an elevated local circulation. A laser Doppler blood flow monitor was employed to measure blood flow changes in healed wounds. It was speculated that local circulation in a developing hypertrophic scar would be elevated. Patients with recently healed wound sites were monitored and exhibited an average blood flow reading of 365 +/- 325 mV (n = 131). This average value, ranging from 98 to 1450 mV, was 18 times greater than the average reading from normal skin, which was 43 +/- 13 mV (n = 212). Blood flow declined to 32 +/- 21 mV (n = 7) at 16 to 18 weeks (74 percent of normal skin values) in healed wounds that developed normal scar. However, a closed wound that developed into a hypertrophic scar had a blood flow reading of 148 +/- 78 mV (n = 59) at 16 to 18 weeks. This value was three times greater than in normal skin and four times greater than in normal scar. At 38 to 50 weeks postinjury, hypertrophic scar remained elevated (102 +/- 34 mV; n = 10). Hypertrophic scars sustain an elevated blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogeny of vasoactive intestinal peptide in the human fetal digestive tract

Immunocytochemistry and radioimmunoassay were used to assess the appearance time and tissue distribution of vasoactive intestinal peptide (VIP) in the digestive tract of the human fetus. By radioimmunoassay, VIP was measurable from 10 weeks of gestation. The peptide was abundantly distributed in the jejuno-ileum and colon, where the tissue peptide concentration rose from 9-14 weeks of gestation (18.4 +/- 4.4 and 22.0 +/- 5.0 pmol/g wet weight, respectively) to 15-21 weeks (83.0 +/- 21.1 and 98.6 +/- 36.4 pmol/g, respectively). Lower concentrations were recorded in pancreas from 9-14 weeks of gestation (4.3 +/- 0.8 pmol/g) to 15-21 weeks (13.9 +/- 3.7 pmol/g). The peptide concentration was 15.6 +/- 1.9 pmol/g in fundus and 25.5 +/- 3.2 pmol/g in antrum from 15 to 21 weeks of gestation. The highest concentration was recorded in duodenum from 15 to 21 weeks of gestation (118.4 +/- 40.8 pmol/g wet weight). Tissue VIP concentration and age were positively correlated in the jejuno-ileum. By immunofluorescence, immunoreactive VIP was localized in nervous fibers in the muscularis externa, in the submucosa and in the lamina propria. Scarce cell bodies were also found in the myenteric plexus. No immunofluorescent endocrine cells were observed. These results suggest: (1) the early appearance of immunoreactive VIP in gut, as early as 10 weeks of gestation; (2) the peptide, localized in nervous structures only, follows the same distribution pattern as that in adults; (3) the development of VIPergic structures is a continuous process, initiated during the 3rd month of pregnancy.     

Selenium concentration in the prostate

Samples of healthy tissue were taken from each of six prostatectomy specimens (55–72 yr), digested with acids, and analyzed for selenium by atomic fluorescence spectroscopy. The concentrations for five specimens were 1.32±0.09 μg Se/g dry wt (range 1.24–1.42) and 0.213±0.012 μg Se/g wet wt (range 0.200–0.229). The other specimen, from a 58-yr-old man who was the only one within this study to take a 200-μg Se/d dietary supplement, contained 2.72 μg Se/g dry wt and 0.421 μg Se/g wet wt.     

Gallium inhibits bone resorption by a direct effect on osteoclasts

Gallium nitrate has been used clinically to treat cancer-related hypercalcemia. It has been suggested that gallium may reduce calcium release from bone by inhibiting bone resorption, but the mechanism(s) involved remain to be elucidated. Therefore, we have examined the effect of gallium on bone resorption in vitro using osteoclasts isolated from neonatal rat long bones cultured on slices of cortical bone. Gallium nitrate (0.01–100 μg/ml) produced a concentration-dependent inhibition of bone resorption. Morphological studies showed that even (100μg/ml) gallium nitrate induced no light microscopical change in osteoclast morphology and did not affect their survival on bone slices. Pretreatment of bone slices with gallium nitrate (100μg/ml for 18 h), followed by extensive washing also inhibited subsequent osteoclastic bone resorption. These results suggest that gallium can be adsorbed onto the calcified surface of bone and inhibit osteoclastic bone resorption.