Although elcatonin increases the bone mineral density, the optimal effective dose of elcatonin in clinical or experimental studies was not established. In most previous studies the bone mineral density was measured only at one time point. In our study, we used the dual X-ray energy absorptiometry to measure the bone mineral density of femur, and also analysed bone metabolism markers such as osteocalcin and deoxypyridinoline (DPD) 119 Wistar-lineage twelve-month-old rats, ovariectomized (91) (high metabolism turnover type) and sham operated (28) were used. Ovariectomized rats were divided into four groups: according to the dose of elcatonin (0, 1, 5, and 25 unit (U)/kg, every other day) untreated, 1U, 5U, and 25U group. The bone mineral density and bone metabolism markers of each group were measured every month after the injection of elcatonin for three months. 25U group showed the greatest increase in bone mineral density after three months. However, poor appetite and hypokinesia were noted in this group from starting month, which decreased the bone mineral density. The bone mineral density of 1U group was slightly increased after injection during the first two months, but decreased after three months. 5U group showed slight decrease in mineral density throughout experimental periods. The levels of both osteocalcin and DPD in all groups were lower than those immediately before administration of elcatonin. Osteocalcin showed greater decrease in 5U group than in 1U group during the first two months, whereas DPD were lower in 5U group than in 1U group after three months. Osteocalcin became higher level in 5U group than in 1U group after three month. Therefore, bone mineral density continuously increased in 1U group during the first two months, and later decreased. In contrast, 5U group was prevented to decrease in bone mineral density throghout three months. In 25U group, both markers were increased one month, and DPD was markedly decreased three months after the administration of elcatonin, whereas osteocalcin showed increased levels, which indicating the largest increase in bone mineral density. Throughout the three months of experimental period, the largest increased in bone mineral density was expected in 25U group, but the decrease in bone mineral density due to side effects such as poor appetite and hypokenesia which was observed one month after starting the administration of elcatonin was a problem. Therefore, the increase in bone mineral density without inducing side effects could be expected in 1U group. It was concluded that the increase in bone mineral density could be expected safely by administering 1U/kg of elcatonin for two months.

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After experimentally inducing osteoporosis in rats, elcatonin(ECT) was administered, and bone strength was measured and bone morphometry performed to ascertain differences in these parameters attributable to admmistration doses and period. In the present experiment, 119 twelve-month-old female Wistar rats were used, with ovariectomy (OVX) being performed on 91 rats. These rats were kept for six more months and used in the experiment after dividing them into five groups: sham ovariectomy group (sham group), 1U/kg elcatonin administration group (1U group), 5U/kg elcatonin administration group (5U group), 25U/kg elcatonin administration group (25U group), and non-administrated group (Non group). The results showed that cancellous bone strength increased significantly in response to administration of elcatonin, and this effect was particularly strong when 1 or 5 U/kg of elcatonin administered for one month. However, there were no clear increases in cortical bone strength. The results of bone morphometry suggest that osteogenesis increased with a low-dose and snort-term administration of elcatonin. The present findings suggest that low dose administration of elcatonin for a short period of time contributes to the prevention of compression fractures by increasing the strength of the vertebral body, which is rich in cancellous bone.

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We examined chromosomal anomalies and PAX6 mutations in 8 pedigrees with aniridia. Chromosomal analysis identified deletions at 11p13 region in two sporadic patients. Seven heterozygous mutations of the PAX6 gene were found by polymerase chain reaction single strand conformation polymorphism assay (PCR-SSCP) and sequencing. Three of the mutations occurred in the paired domain (one stop codon, one splice junction error and one frameshift) and one in the proline-serine-threonine-rich domain (one stop codon). Affected members of each family who had the same mutation, showed various phenotypes. Together with clinical features of sporadic cases, there was no correlation between genotype of PAX6 mutations and phenotype of the eye anomalies. These mutations found in the present study, which predict truncated proteins support that aniridia is caused by haploinsufficiency of the PAX6 gene.

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The present authors attempted to determine whether nephrotoxicity could be produced in fetal rats via injection of glutamate into amniotic sacs at a late stage in gestation. Glutamate is both an excitatory neurotransmitter and a neurotoxin. We used enzyme histochemistry to determine whether any alteration of alkaline phosphatase (ALPase) activity, an index of nephrotoxity, occurred in the kidneys of fetal and postnatal rats. Glutamate or saline were injected into the amniotic sacs of fetal rats on the 15th day of gestation. Three hours and 2, 5 and 34 days after administration of glutamate, saline or nothing(control), the kidneys of fetal and postnatal rats were removed, ALPase histochemistry was performed and the tissue was observed under light and electron microscopy. The results showed that at 3 hours and 2 days (17th day of gestation), in glutamate treated and control fetal rats, ALPase activity was localized to a few tubules in the inner cortex of the kidney. Intensity of ALPase activity was weak in both glutamate treated and control fetal rats. No differences were observed with regard to ALPase activity between the two groups. At 5 days (20th day of gestation), ALPase activity was localized to a few proximal tubules in the inner cortex of the kidney and the observed intensity was weak in glutamate treated fetal rats, whereas in control fetal rats, activity was detected in numerous proximal tubules throughout the entire inner cortex of the kidney and the observed intensity was strong. At 34 days (28th postnatal day), ALPase activity was detected in numerous proximal tubules throughout the entire cortex of the kidney and the observed intensity was strong in both glutamate treated and control rats. No differences were observed with regard to ALPase activity between the two groups. These results suggested that the observed functional disorder, namely nephrotoxicity of the proximal tubules of fetal kidney at 5 days after administration of glutamate, which was detected as a diminution of ALPase activity, might have been caused by temporary glutamate exposure during a late stage in gestation. Moreover, proximal tubules of the kidney that had suffered glutamate damage showed a recovery of function at 34 days after the glutamate treatment. Given that the changes in ALPase activity in the proximal tubules at 5 days after treatment of glutamate preceded morphological changes. ALPase histochemistry may be useful as an early and sensitive index of nephrotoxicity during renal development.

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To assess the disease-state of purulent osteomyelitis, 102immature Japanese white rabbits were used to prepare experimental osteomyelitis models. While osteomyelitis was experimentally induced, body weight was measured, X-rays taken and blood tests conducted. Blood tests were performed to ascertain changes in the levels of serum prostaglandin (PGE2) and serum anti-Staphylococcus aureus IgG antibody titer. Based on the results, rabbits were classified into four groups: osteomyelitis was not experimentally induced (control group), osteomyelitis did not occur (no onset group), osteomyelitis improved naturally (improved group), and osteomyelitis was exacerbated (exacerbated group). For the control and no onset groups, the level of serum IgG antibody titer did not increaseat week 16, remaining essentially constant between 0.36 and 0.56. For the improved group, it increased to 0.62 at week 8, and then decreased gradually after that. For the exacerbated group, the level of serum IgG antibody titer started to increase rapidly at week 4 and it remained high at 0.72 at week 8 and beyond. There were significant differences in the level of serum IgG antibody titer between the exacerbated and other groups. For the control and no onset groups, the level of serum PGE2 fluctuated within 10 and 2 pg/dl and did not change markedly. For the improved group, the level of serum PGE2 was about 240-860 pg/dl between weeks 4 and 6, whereas that for the exacerbated group was increased at about 5,500 pg/dl at week 4. These findings suggest that changes in the levels of serum IgG antibody titer and serum PGE2 are important markers of the disease-state of experimental osteomyelitis.

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A female child with congenital central hypoventilation syndrome (CCHS) associated with Hirschsprung disease (HSCR) was examined for her genomic DNA in the coding region of the receptor tyrosine kinase (RET) and the endothelin-B receptor (EDNRB) genes. No disease causative mutation was detected but a single nucleotide polymorphism was observed in exon 11 of the RET proto-oncogene. In case with CCHS, HSCR occurs with a high incidence, and this disease complex have been described as neurocristopathies due to aberrations in neural crest cell proliferation, differentiation or migration during early fetal periods. Both of the RET and EDNRB genes may be involved in the modulation of neurocristopathies. However, further systemic studies in a large population of patients should be necessary to elucidate the pathogenesis of the disorder.

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Single pulse transcranial magnetic stimulation (sTMS) was performed in 23 patients with a diagnosis of Major Depressive Episode according to Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) diagnostic criteria, and clinical effects of this treatment were evaluated using the Hamilton Rating Scale for Depression (HAM-D). Antidepressant dose levels were maintained without change from 1 month before sTMS until 15 days after treatment. Results showed that sTMS was associated with lower HAM-D scores in all but 1 of the treated patients. Effects of sTMS were favorable even for major and therapeutically problematic symptoms such as depressed mood, psychomotor retardation, feelings of excessive or inappropriate guilt, and suicidal ideation or attempted suicide. In addition, sTMS was found to be effective in the elderly and in patients who had undergone numerous Major Depressive Episodes. Such cases are ordinarily considered relatively refractory to treatment. No notable adverse reactions were observed in any of the patients treated. These results suggest that this treatment is as effective as electroconvulsive therapy (ECT), and that sTMS has broad applications for patients suffering from depression.

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An artificial dermal substitute composed of a xenogenous collagen sponge has been widely used to create a dermal component in a full-thickness skin wound. However, one of the disadvantages in using the dermal substitute is that it requires a 2-stage surgical procedure for final wound closure. In order to close the wound much more rapidly, another type of dermal substitute which enables a simultaneous skin graft overlay is needed. In the present study, we investigated the effect of a collagen sponge seeded with isogenic fibroblasts on a simultaneously overlaid skin graft in a rat model. Normal dermal fibroblasts of SD rat were seeded and cultured on a collagen sponge composed of cross-linked porcine type I collagen. Full-thickness skin wounds were created on the dorsum of SD rats. The collagen sponges with or without fibroblasts were placed in the wounds, then covered simultaneously with split-thickness skin graft (STSG) , At 1 week and 4 weeks after grafting, overlaid STSG survival TGF-β1 level, wound contraction, final re-epithelization and histology of the grafts were studied. The overlaid STSG survived moderately but the seeded fibroblasts did not enhance the STSG survival rate. Also, there were no significant differences in wound contraction and in the final wound epithelization between the collagen sponge seeded with and without fibroblasts. Both collagen sponges with and without fibroblasts developed neo-dermal structure without any specific immunological reaction. However, the fibroblast-seeded collagen sponge grafts showed significant re-epithelization along the junctional surface between the collagen sponge and the STSG by out-growing of the hair follicle cells. This epithelization seemed to result in formation of epithelial inclusion cysts in the neo-dermis. It was suggested that the seeded fibroblasts strongly induced such an epithelial outgrowth. The cultured collagen sponge may have beneficial effect on re-epithelization in a certain type of simultaneous skin graft overlay such as meshed STSG.

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Taste thresholds and factors related with sense of taste were investigated in 68 elderly subjects (aged 65-74, male: 23, female: 45) in the community at Yokohama area, Kanagawa Prefecture in Japan. The taste test of salt by the questionnaire survey, the blood biochemistry test, the dental test, and whole mouth method was executed to all subjects. Taste test on salt was conducted by the whole mouth method 2 hours after their lunch to measure detection threshold (DT) and recognition threshold (RT). Mean DT and RT on salty taste were 3.7mM and 25.2mM for male and 2.2mM and 27.4mM for female, respectively. In female subjects, increased number of missing teeth tended to show higher DT (p<0.01). RT higher than 0.7% salt solution was defined as potentially decreased sense of taste and was found in 5 subjects (7.4%). Zinc defficiency was known as a main cause of taste disorders in the clinical settings. Although 9 subjects revealed low plasma concentration of zinc less than 0.8 ppm, no correlation with DT or RT was found. In conclusion, dental condition was the major factor affecting the sense of taste in the elderly. Since it was not clear about clinical meanings of low plasma zinc in the elderly, the follow-up study concerning the taste sensitivity and the plasma zinc levels among larger community was needed.

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