Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 109 records · Page 6Linked to original sources

PubMed1998

Serum protein binding kinetics of phenytoin in monotherapy patients.

OBJECTIVES: To determine the binding characteristics of phenytoin to serum proteins in the Japanese population and to compare these with those reported by other investigators. METHOD: Serum samples examined in the study were obtained from 72 patients (35 males, 37 females) receiving phenytoin monotherapy. The patients' ages ranged from 1 to 73 years (1-15 years, 36 subjects; 16-44 years, 20 subjects; 45-64 years, 13 subjects; > or = 65 years, 3 subjects). RESULTS: The in vivo population binding parameters of phenytoin to serum proteins and theoretical minimal unbound serum phenytoin fraction (fu) were determined using the Scatchard equation. The association constant (K) was 0.020 1/micromol, while the total concentration of binding sites (n(Pt) was 556 micromol/l. The number of binding sites per albumin molecule (n) was 0.85, while binding ability (n.K) was 0.017 l/micromol. The fu was 0.083. The n.K is approximately 1.1 times higher in patients of Pospísil et al. (26) (i.e. 0.0191 l/micromol) than in all our patients. The association constant is approximately 1.1 times higher in our study than in the in vitro study of Monks et al. (23) (i.e. 0-0186 l/micromol), while n is similar between the two studies. The fu in our patients is similar to the unbound serum phenytoin fraction in adult patients receiving phenytoin therapy reported by Richens (2) (i.e. 0.1). CONCLUSION: Our results suggest that there may be small differences in the binding characteristics of phenytoin to serum proteins between Japanese and non-Japanese subjects. The unbound serum fraction of phenytoin in our patients with epilepsy can be assumed to be relatively constant in the therapeutic concentration range of phenytoin.

Adolescent↗

PubMed1998

Two patients with premature labour associated with Mycoplasma hominis infection.

Because several reports have suggested that bacterial vaginosis causes premature labour and early rupture of the fetal membranes, the presence of a bacterial flora that causes bacterial vaginosis is thought to be a risk factor for premature labour. The present study investigated two patients with premature delivery and intra-uterine Mycoplasma hominis infection. In microbiological studies, Gram's staining of amniotic fluids revealed numerous neutrophils and epithelial cells but no micro-organisms. Culture of amniotic fluid before antibiotic therapy yielded only M. hominis under anaerobic conditions; aerobic culture was negative. Vaginal discharge taken on the day of delivery yielded no growth in case 1 and M. hominis and Enterococcus faecalis in case 2. Maternal sera showed specific antibodies to M. hominis by ELISA and immunoblotting. As no possible cause of premature labour other than M. hominis infection was detected, it is concluded that the intra-uterine M. hominis infection was associated with premature labour in these patients.

Adult↗

PubMed1998

A euthymic hairless mouse model of Helicobacter pylori colonization and adherence to gastric epithelial cells in vivo.

The hairless mouse strain NS:Hr/ICR was examined as a potential small animal model of Helicobacter pylori colonization, adherence to gastric epithelial cells in vivo, and gastritis. Among several small animals tested, NS:Hr/ICR mice proved to be the most highly susceptible to H. pylori infection. Challenge with clinical isolates of H. pylori consisting of either phenotype I or II (VacA and CagA positive and negative, respectively) resulted in colonization by mucus-resident and epithelial cell-adherent bacterial populations. Cell-adherent bacteria resisted 80 cycles of top-speed Vortex washing and were recovered only by homogenization of serially washed glandular stomach tissue, indicating intimate association with the mucosal surface. Immunoperoxidase staining of paraffin sections of gastric tissue from infected mice revealed H. pylori antigens localized in the glandular region of the mucosa, with some colonized areas seen in the vicinity of submucosal mononuclear cell infiltration. The latter inflammatory reaction was observed as a function of the H. pylori phenotype (only type I induced inflammation) and the challenge dose (only those mice challenged with 10(8) CFU or higher showed the reaction). The NS:Hr/ICR strain of mice is a suitable miniature model of H. pylori infection and may prove useful in the quest for an efficacious mode of treatment for this common infection in humans.

Animals↗

PubMed1998

Reduced expression of interleukin-11 in bone marrow stromal cells of senescence-accelerated mice (SAMP6): relationship to osteopenia with enhanced adipogenesis.

Aging is associated with an increase in bone marrow adipose tissue and a reduction in bone turnover. The P6 strain of senescence-accelerated mice (SAM) exhibit an early decrease in bone mass with a reduction in bone remodeling. In the bone marrow, suppressed osteoblastogenesis and osteoclastogenesis with enhanced adipogenesis are observed. The present study was undertaken to clarify the mechanism of age-related changes in bone turnover using bone marrow cells from SAMP6 mice. Because interleukin (IL)-11 has been shown to potently inhibit adipogenesis and to stimulate osteoclast formation, the effect of IL-11 on the differentiation of bone marrow cells was examined. The impaired formation of both osteoblasts and osteoclasts was restored and the enhanced formation of adipocytes was suppressed by the addition of 10 pM recombinant human IL-11. Other cytokines that activate gp130 as a common signal transducer, IL-6 and leukemia inhibitory factor, did not have such effects. Sequence analysis of the entire coding region of IL-11 cDNA obtained from SAMP6 stromal cells revealed no mutations. Constitutively secreted IL-11 protein into culture media, and its mRNA expression stimulated by transforming growth factor beta were reduced in stromal cells from SAMP6 compared with those in control mice. These results demonstrate that the expression of IL-11 is reduced in bone marrow cells of SAMP6 and suggest that the reduction in IL-11 actions is involved in the impairment of both osteoblastogenesis and osteoclastogenesis in these mice. There is a possibility that alterations in IL-11 actions may be associated with the age-related impairment in bone metabolism.

Adipose Tissue↗

PubMed1998

Induction of sister-chromatid exchange by ethylene glycol monomethylether and its metabolite.

The frequency of sister-chromatid exchange (SCE) induced by ethylene glycol monomethylether (EGME) and methoxyacetic acid (MAA), a major metabolite of EGME, was determined in human peripheral blood, and for EGME in mouse bone marrow cells. In the experiment on the human peripheral blood, the induction of SCE was observed after the addition of MAA to the culture medium, but not after the addition of EGME. However, EGME induced SCE in the mouse bone marrow cells, when administered by intraperitoneal injection. These results suggested that EGME did not induce SCE itself, but that MAA, one of the major metabolites of EGME induces SCE.

Acetates↗

PubMed1998

Prevention of fatal salmonellosis in neonatal calves, using orally administered chicken egg yolk Salmonella-specific antibodies.

OBJECTIVE: To protect neonatal calves against fatal salmonellosis within the first 2 weeks after birth, using chicken egg yolk antibodies specific against Salmonella typhimurium or S dublin. ANIMALS: 38 neonatal Holstein calves from Salmonella-free farms. PROCEDURE: After removal of the lipid components with hydroxypropylmethylcellulose phthalate, egg yolk antibodies were spray dried. At 4 days of age, calves were challenge exposed by oral inoculation with 10(11) virulent S typhimurium (experiment 1) or S dublin (experiment 2). Starting from the challenge-exposure day, egg yolk antibody preparations were administered orally 3 times a day for 7 to 10 days. RESULTS: In passive immunization trials, the orally administered antibodies conferred dose-dependent protection against infection with each of the homologous strains of Salmonella. Within 7 to 10 days after challenge exposure, all control calves died, whereas low-titer antibody-treated calves had 60 to 100% mortality. Only fever and diarrhea, but no deaths (P < 0.01), were observed in calves given the highest titer of antibody. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with that in control calves, survival was significantly higher among calves given antibodies with titers of 500 (P < 0.05) and 1,000 (P < 0.01) homotypic for S typhimurium and with titer of 5,000 (P < 0.01) for S dublin. Egg yolk antibodies specific for whole cell S typhimurium or S dublin are protective against fatal salmonellosis when given in sufficiently high concentration, and may be clinically useful during a salmonellosis outbreak.

Administration, Oral↗

PubMed1998

[A case of acute polyradiculoneuritis with multiple cranial nerve palsy and cerebral lesion--possible evidence of encephalo-myelo-radiculo-neuropathy].

We report a case of acute polyradiculoneuritis with multiple cranial nerve palsy and cerebral lesions. A boy, born on July 26, 1987, developed unusual sensation on the extremities, backache and sleep disturbance on June 23, 1996. On July 2, following a complaint of blindness he developed a convulsion and was admitted to our hospital. Neurological examination revealed intact consciousness, severe external ophthalmoplegia, bifacial palsy and generalized areflexia. On the next day, flaccid tetraplegia and respiratory dysfunction developed and progressed without disturbance of consciousness. After tracheal intubation he was under mechanical ventilation. A lumbar puncture examination showed clear CSF with increased protein 166 mg/dl. no cells and normal myelin basic protein. Serum antibodies against gangliosides (GM1, asialo-GM1, GD1b and GQ1b) were not detected. A posterior tibial nerve conduction velocity was mildly delayed with disappearance of F- wave. On the other hand, very slow background activity was shown by EEG, extensive focal hypoperfusion of cerebral blood flow by SPECT and supratentorial multiple high intensity lesions by T2 weighted MRI of the brain. There were no abnormal signals in the brainstem and cerebellum on MRI. His condition dramatically improved after plasmapheresis. The abnormal findings of SPECT and MRI promptly disappeared within 3 weeks, although abnormal signs on EEG persisted. He was successfully weaned off the respirator and recovered strength of the limbs. He was discharged on August 28, 1996, with supported walk and bifacial palsy, then he completely recovered by 7 months. The condition of case was compatible with 'encephalo-myelo-radiculo-neuropathy', a disease entity that had previously been reported in a few patients in whom with Guillain-Barré or Fisher syndrome and cerebral symptoms co-existed.

Acute Disease↗

PubMed1998

[A case of allergic cross reaction between tricyclic antidepressants and maprotiline].

Although a 76-year-old woman with a diagnosis of depression began a course of maprotiline, the drug was discontinued after 14 days when she developed a rash. She was started on lofepramine in substitution for maprotiline. Four years later, lofepramine treatment was stopped and to amoxapine treatment introduced due to the aggravation of depressive symptoms. On the second day of this regimen, she developed a pruritic rash. She stopped the medication immediately. Because the rash disappeared gradually, lofepramine treatment was restarted. But her recovery was restrained and new skin lesions developed. Again, she stopped the medication, and the rash cleared within several days. This case suggests the existence of cross-allergenicity between tricyclic antidepressants and maprotiline.

Aged↗

PubMed1997

Photoaffinity labeling of peroxisome proliferator binding proteins in rat hepatocytes; dehydroepiandrosterone sulfate- and bezafibrate-binding proteins.

To detect the cellular sites which directly interact with peroxisome proliferators (PPs) and mediate their inducing effect on peroxisomal enzymes in rat hepatocytes, two kinds of radiolabeled ligands, AD12 (7alpha-N-(4-azido-2-hydroxy-5-iodo[125I]benzyl)-aminomethyl-5-and rostene-3beta-ol-17-one-O-3-sulfate) and BZ5 (2-[p-[2-(4'-azido-3',5'-diiodo[125I]benzamido-2'-hydroxy)ethyl]phenoxy] -2-methylpropionic acid), were developed for photoaffinity labeling. These compounds were derivatives of dehydroepiandrosterone sulfate (DHEAS) and bezafibrate, respectively, with an azido group as the photoreactive functional group. Upon UV-irradiation following incubation with rat liver cytosol and nuclei, both the ligands effectively radiolabeled several proteins analyzed by SDS-polyacrylamide gel electrophoresis/radioluminography. When [125I]AD12 was used at a concentration of 0.2 microM, two cytosolic proteins with molecular masses of 55 and 28 kDa and a nuclear protein of 40 kDa were specifically labeled, as coincubation with a 1000-fold excess of DHEAS inhibited labeling. Photoaffinity labeling of the cytosolic 28-kDa protein was also affected by Wy-14,643, but not by unsulfated dehydroepiandrosterone or androsterone sulfate, consistent with our previous findings obtained in competitive binding studies of [3H]DHEAS-binding detected in rat liver cytosol (Yamada et al. (1994) Biochim. Biophys. Acta 1224, 139-146). On the other hand, [125I]BZ5 specifically labeled a cytosolic protein of 31 kDa, which was inhibited by coincubation with bezafibrate, clofibric acid and Wy-14,643, but not with DHEAS. Thus, [125I]AD12 and [125I]BZ5 labeled several proteins which recognized DHEAS and bezafibrate, respectively, in rat liver cytosol and nuclei, providing a useful means to investigate PP-binding proteins.

Affinity Labels↗

PubMed1997

Video-rate dynamics of exocytotic events associated with phagocytosis in neutrophils.

Exocytotic responses associated with phagocytosis were investigated in a single neutrophil with a special reference to their dynamic properties and their spatiotemporal relationships with ionic and chemical responses during phagocytosis. The real-time sequence of phagocytosis-exocytosis was directly visualized by video-enhanced contrast differential interference contrast (VEC-DIC) microscopy. The actual release of contents from such a granule was proven by examining a cell loaded with quinacrine with a dual imaging system that allowed us to observe DIC and fluorescence images simultaneously at a high magnification. During the process of phagosome formation in a neutrophil engulfing an opsonized zymosan, the exocytotic response was observed first in a granule located near the cell surface initially attached to the zymosan, and then in other granules sequentially along pseudopodia surrounding the zymosan. When the phagocytosis was induced in a medium containing luminol, a chemiluminescence due to active oxidants was detected exclusively in the region of phagosome, suggesting that exocytosis took place on the phagosomal membrane and not on the plasma membrane. Changes in cytosolic free calcium concentration ([Ca2+]i) were further measured using fura-2 under the dual imaging system. [Ca2+]i transients were more closely related to the extension of pseudopodia for engulfing zymosan and not directly to the exocytosis. These findings lead to a conclusion that exocytosis associated with phagocytosis is initiated by attachment of the cell membrane to the invading organism and mediated by local activation of the phagosomal membrane.

Animals↗

PubMed1997

Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors.

To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injection of 60 mg of vinyl carbamate (VC)/kg body weight or saline (vehicle control) and monitored for 16 wk without further treatment. At necropsy, grossly visible tumors were fixed for histopathologic diagnosis and, when of sufficient size, portions were frozen for subsequent molecular analysis. Nine of 31 male and nine of 29 female Hras2 mice treated with VC died within 16 wk as a result of lung tumor burden. At the termination of the study, lung tumors (alveolar-bronchiolar epithelial neoplasms and hemangiosarcomas) and focal alveolar-bronchiolar hyperplasias were present in both sexes of Hras2 and non-Tg mice treated with VC; there were significantly more proliferative lung lesions in Hras2 than non-Tg mice. Splenic hemangiosarcomas and squamous cell tumors of the forestomach were induced in male and female VC-treated Hras2 mice but not in VC-treated non-Tg mice. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing of the induced lung tumors revealed point mutations at codon 61 of the transgene in two of 29 lung tumors (one of 16 in males and one of 13 in females) from VC-treated Hras2 mice; no mutations in murine Ki-ras were found in these tumors. Point mutations at codons 12 and 61 of the murine Ki-ras gene were observed, however, in one of 10 and six of 10 lung tumors respectively, from VC-treated non-Tg mice. These findings indicate that Hras2 mice are highly sensitive to pulmonary neoplasms and splenic and lung hemangiosarcomas after treatment with VC. The molecular analyses suggest that point mutations of the transgene and the murine Ki-ras gene do not play a major role in VC induction of pulmonary neoplasms in these transgenic mice.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1997

Pro-inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin.

Pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 and IL-6 are thought to play important roles in the pathophysiology of chronic kidney disorders, including glomerulonephritis. In particular, IL-6 has received considerable attention as it appears at high concentrations to promote the progression of renal disease while at lower levels may be involved in regulating repair mechanisms. As such, cytokine profiles have been examined in the kidney by either examining secretion from isolated kidney cells or quantitating plasma and urinary levels in experimental models of glomerulonephritis. To examine the cytokine responses within the kidney, without the contribution of other organ systems, we used semi-quantitive polymerase chain reaction (RT-PCR) analysis and a recently developed kidney slice culture model from tissues of mice treated with combinations of endotoxin and neutralizing antibodies against TNF-alpha. The expression of IL-6, in addition to other pro-inflammatory cytokine genes, was increased by endotoxin treatment and reduced by pretreatment with neutralizing antibodies to TNF-alpha. Immunohistochemical staining revealed that IL-6 was expressed primarily in mesangial cells. Urinary IL-6 was also increased in endotoxin-treated mice and was inhibited by treatment with neutralizing TNF-alpha antibodies. Kinetics of the kidney-specific cytokine responses indicated that increase in TNF-alpha occurred initially, followed by IL-1 beta and finally IL-6. Furthermore, addition of TNF-alpha to glomerular mesangial cells induces IL-6 secretion. Taken together, these studies indicate that, like in the liver, a cytokine response occurs in the kidney from bacterial endotoxin and that TNF-alpha acts as a primary cytokine capable of stimulating additional cytokines, including IL-6.

Animals↗

PubMed1997

Field evaluation of chicken egg yolk immunoglobulins specific for bovine rotavirus in neonatal calves.

The oral efficacy of chicken egg yolk immunoglobulins (yIg) specific for bovine rotavirus (BRV) serotypes G6 and G10 in protecting neonatal calves was examined in a herd of cattle under field conditions. In one of the three trials, yIg-treated calves tested under high relative humidity (RH) showed a significantly increased mean body weight (P < 0.05) and a decrease in number of calves shedding high titer of BRV (G6) in stool compared to control calves (P < 0.01), suggesting that our yIg product was effective in a field condition with an epidemic outbreak of BRV diarrhea.

Animals↗

PubMed1997

Passive protection of neonatal calves against bovine coronavirus-induced diarrhea by administration of egg yolk or colostrum antibody powder.

The protective effect of egg yolk and colostrum powders prepared from hens and cows vaccinated with inactivated bovine coronavirus (BCV) antigen was evaluated in a challenge model with a virulent BCV strain. Twenty three calves from BCV-free herds were randomly divided into control and several treatment groups. All calves were orally challenged with 1 x 10(9) TCID50 of the virulent Kakegawa strain of BCV at 24 to 36 h after birth. Calves in treatment groups received either egg yolk powder or cow colostrum containing BCV specific antibodies. Daily treatment with these antibody preparations started 6 h until 7 days post-challenge. Control calves which received no antibody had severe diarrhea and all died within 6 days after infection. In contrast, calves fed milk containing egg yolk or colostrum with neutralization titers of 1:2560 or 1:10,240 respectively all survived and had positive weight gain unlike the other treatment groups. These results indicate that the orally administered egg yolk and colostrum powders protected against BCV-induced diarrhea in neonatal calves and that the egg yolk used provided a higher degree of protection compared to colostrum powder on a titer basis. Treatment with whole egg yolk from immunized hens therefore provides a more efficacious alternative to the existing methods of specific passive protection against BCV.

Animals↗

PubMed1997

Estimation of minimal size of translocated chromosome segments detectable by fluorescence in situ hybridization.

Apparent non-reciprocal translocations are commonly observed using fluorescence in situ hybridization. We hypothesize that these are 'hidden' reciprocals due to one translocated segment being too small to detect. Assuming that the translocation breakpoints distribute randomly, the proportion of reciprocal to non-reciprocal exchanges can be used to estimate the minimal detectable size of translocated segments. To estimate segment size in this study, cytogenetic data for 120 A-bomb survivors were used. Among 2295 aberrant metaphases, 1629 exhibited reciprocal translocations and 666 non-reciprocal. Of the non-reciprocal translocations, 501 showed only a painted chromosome segment, translocated to an unpainted chromosome with centromere, and 165 showed only an unpainted chromosome segment, translocated to a painted chromosome with centromere. On the basis of the above two assumptions, we obtained the most likely estimates for minimal detectable sizes: 11.1 +/- 0.8 Mb for the painted and 14.6 +/- 0.6 Mb for the unpainted chromosomes. The implications of these findings are discussed.

Humans↗

PubMed1997

Chronic anti-ataxic actions of the novel thyrotropin-releasing hormone (TRH) analog, TA-0910, during and after repeated administration in Rolling mouse Nagoya: behavioral and pharmacokinetic studies.

Anti-ataxic effects of TA-0910, a novel thyrotropin-releasing hormone analog, in mice of the ataxic mutant mouse strain Rolling mouse Nagoya (RMN) are sustained beyond its 2-week oral administration period (Kinoshita et al., Eur. J. Pharmacol., 274, 65-72, 1995). We examined the concentration of TA-0910 in the central nervous system (CNS) of RMN after repeated administration in an attempt to clarify the mechanism of the sustained effect of the drug. Repeated administration of TA-0910 (3 mg/kg/d, i.p.) for 2 weeks produced a long-lasting ameliorating effect on ataxia in RMN, and this effect was maintained until 3 weeks after drug withdrawal. The concentrations of TA-0910 in the cerebrum and brain stem 24 h after the final administration were twice the concentration observed 24h after single administration. The cerebellum cencentration of TA-0910 was more than 4 times that observed 24 h after final administration. After repeated administrations, the drug concentrations in the brain tissues gradually decreased, but the drug was still detectable in the cerebrum and brain stem 3 weeks after withdrawal. However, these concentrations of TA-0910 3 weeks after withdrawal were as low those observed 24 h after single administration when there were no anti-ataxic effects. These observations suggest that the long-lasting ameliorating effect on the ataxia during and after repeated administration of TA-0910 is not ascribable to the drug remaining in the CNS of RMN.

Animals↗

PubMed1997

Effect of oral egg antibody in experimental F18+ Escherichia coli infection in weaned pigs.

The protection conferred by egg antibody specific for F18-fimbriae against infection with F18+ Escherichia coli was studied in controlled passive immunization trials involving weaned pigs. Parameters of protection consisted of body weight gain, frequency and severity of diarrhea and recovery of the challenge strain of F18+ E. coli. Weaned pigs at four weeks of age were challenge exposed once daily for three days by oral inoculation with 10(11) cfu of virulent F18+ E. coli followed by daily administration of antibody supplemented feed for 9 days starting from the first challenge day 0. Results showed a dose-dependent response to antibody treatment. The group of pigs given 1:50 titer of antibody in feed had less frequency of diarrhea (P < 0.01-0.05), higher rate of gain (P < 0.01) and lower isolation rate of challenge strain in rectal and intestinal swabs (P < 0.01) compared to non-treated control. In the same manner, the anti-F18 antibody significantly reduced adherence of F18+ E. coli to pig intestinal epithelial cells in vitro (P < 0.01). Results suggest that egg antibodies specific for the F18 fimbriae is a suitable immunotherapeutic agent for pigs infected with F18+ E. coli and that pigs can be protected from overt clinical disease and the subsequent reduced performance arising from infection with this pathogen.

Administration, Oral↗

PubMed1997

Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats.

To clarify how the changes in bone formation and resorption affect bone volume and strength after mechanical unloading, the effect of inhibition of bone resorption by a potent bisphosphonate, pamidronate, on bone mineral density (BMD), histology, and strength of hind limb bones was examined using tail-suspended growing rats. Tail suspension for 14 days reduced the gain in the BMD of the femur at both the metaphysis rich in trabecular bone and the diaphysis rich in cortical bone. Treatment with pamidronate increased the total BMD as well as that of the metaphysis of the femur but had almost no effect on the BMD of the diaphysis in both control and tail-suspended rats. Histological examinations revealed that 14-day tail suspension caused a loss of secondary cancellous bone with a reduction in the trabecular number and thickness in comparison with control rats. In the femoral diaphysis, the diameter and cortical bone thickness increased to a lesser degree in tail-suspended rats when compared with rats without tail suspension, and a marked reduction in bone formation and the layers of alkaline phosphatase-positive cells was observed at the periosteal side. Pamidronate treatment increased secondary cancellous bone but could not restore normal growth-induced periosteal bone apposition and bone strength. Because the material strength of the femoral diaphysis at the tissue level was not affected by pamidronate treatment, the inability of pamidronate to prevent the reduction in physical strength of the femoral diaphysis does not appear to be due to a change in the quality of newly formed bone. These results demonstrate that tail suspension reduces the growth-induced periosteal modelling drift and that the antiresorptive agent pamidronate is unable to restore normal periosteal bone apposition.

Amino Acids↗