Effects of combined oral treatments with cyclosporine A and nifedipine or diltiazem on drug-induced gingival overgrowth in rats.

BACKGROUND: Cyclosporine A (CsA) and calcium channel blockers induce gingival overgrowth in humans and animals. Recently, nifedipine and diltiazem have often been used to control CsA-related hypertension in organ transplant patients. The purpose of this study was to examine the effects of a combined oral treatment of CsA and nifedipine or diltiazem on the severity of gingival overgrowth in rats. METHODS: Fifteen-day-old Fischer rats were treated orally with single or combined applications of CsA, nifedipine, and/or diltiazem for 40 days; and induced gingival overgrowth, rat growth, and blood drug levels were compared among the different experimental groups. The experiment consisted of 6 groups: one control group (group A) and 5 test groups treated with CsA (group B), nifedipine (group C), and diltiazem (group D), as well as those concurrently treated with CsA and nifedipine (group E), and CsA and diltiazem (group F). Gingival overgrowth was determined by measuring the depth of the gingival sulcus. RESULTS: The mandibular buccal gingival sulcus depth of group A was 365 +/- 41.2 microm. Among the test groups, the most remarkable gingival overgrowth was seen in group E (1,020 +/- 63.3 microm), followed by group F (895 +/- 43.8 microm), group B (870 +/- 48.3 microm), group C (525 +/- 116 microm), and then group D (505 +/- 83.2 microm). Rat body weight gain was reduced significantly by oral CsA treatment. Neither nifedipine nor diltiazem suppressed rat growth when used independently; however, rat growth reduced by CsA was further suppressed by a combined use of diltiazem, but not nifedipine. CsA blood levels were reduced by concurrent oral treatment with nifedipine or diltiazem along with the blood levels of those calcium channel blockers when treatment was in combination with CsA. CONCLUSIONS: These results suggest that gingival overgrowth is induced in rats as a side effect of CsA, nifedipine, or diltiazem, and the combined use of these drugs influences rat growth, blood drug levels, and the severity of gingival overgrowth.

Oral findings in DiGeorge syndrome: clinical features and histologic study of primary teeth.

OBJECTIVE: For the purpose of supplementing the shortage of dental information about DiGeorge syndrome, we report two cases of the syndrome seen in Japanese boys. STUDY DESIGN: Two cases were compared with respect to orofacial and dental findings; one was a case of complete DiGeorge syndrome and the other a case of partial DiGeorge syndrome. Extracted deciduous teeth from the two boys underwent histologic study. RESULTS: Each patient showed systemic developmental delay, hypocalcemia, and slight mental retardation. In the orofacial area, hypertelorism, a short philtrum, thick and reflected lips, and hypoplasia of the nasopharynx were also observed. A dental examination showed delayed formation and eruption of permanent teeth, aplasia of the nasopharynx, and enamel hypoplasia along with enamel hypocalcification. Structural streaks with increased calcification were histologically detected in the deciduous tooth from the patient with complete DiGeorge syndrome. CONCLUSIONS: Common characteristic orofacial and dental findings were noted in the two DiGeorge syndrome cases. Furthermore, histologic study of the deciduous tooth from the boy with complete DiGeorge syndrome suggests that there was some relationship between transient relative hypercalcemia and dentinal hypermineralized streaking of the tooth.

Immunohistochemical localization of carbonic anhydrase isozyme II in the gustatory epithelium of the adult rat.

The distribution of carbonic anhydrase isozyme II (CA II)-like immunoreactivity (-LI) in the gustatory epithelium was examined in the adult rat. In the circumvallate and foliate papillae, CA II-LI was observed in the cytoplasm of the spindle-shaped taste bud cells, with weak immunoreaction in the surface of the gustatory epithelium. No neuronal elements displayed CA II-LI in these papillae. There was no apparent difference in the distribution pattern between the anterior and posterior portions of the foliate papillae. In immunoelectron microscopy, immunoreaction products for CA II were diffusely distributed in the entire cytoplasm of the taste bud cells having dense round granules at the periphery of the cells. No taste bud cells displaying CA II-LI were detected in the fungiform papillae, but a few thick nerve fibers displayed CA II-LI. In the taste buds of the palatal epithelium, neither taste bud cells nor neuronal elements exhibited CA II-LI. The present results indicate that CA II was localized in the type I cells designated as supporting cells in the taste buds located in the posterior lingual papillae of the adult animal.

Immunohistochemical observation of growth-associated protein 43 (GAP-43) in the developing circumvallate papilla of the rat.

The distribution and development of growth-associated protein 43 (GAP-43)-like immunoreactivity (-LI) in the rat circumvallate papilla (CVP) were compared to those of protein gene product 9.5 (PGP 9.5)-LI. In the adult, thick GAP-43-like immunoreactive (-IR) structures gathered densely in the subgemmal region. Some of these further penetrated the apical epithelium and trench wall epithelium. At least two types of GAP-43-IR structures were recognized; taste bud-related and non-gustatory GAP-43-IR neural elements. Immunoelectron microscopy revealed that GAP-43-LI was localized predominantly in the Schwann cells, and a few axons displayed GAP-43-LI in the lamina propria. In the trench epithelium, GAP-43-LI was detected in the cytoplasmic side of the axonal membrane. Some intragemmal GAP-43-IR axons made synaptic-like contacts with taste bud cells. At least four developmental stages were defined on the basis of the changes in distribution of GAP-43-LI. In stage I [embryonic day (E) 16-17] GAP-43-IR structures accumulated at the lamina propria just beneath the newly-formed circumvallate papilla. In stage II (E18-19) GAP-43-IR nerve fibers began to penetrate the apical epithelium. In stage III [E20-postnatal day (P) 0] GAP-43-IR nerve fibers first appeared in the trench wall epithelium. Penetration of GAP-IR nerve fibers occurred in the inner trench wall epithelium first, and then in the outer trench wall epithelium. In stage IV (P1-) the distribution of GAP-43-LI was similar to that observed in the adult; but the density of GAP-43-LI was much higher than in adults. PGP 9.5-LI showed a similar distribution pattern to that of GAP-43-LI, except for round-shaped cells in the apical epithelium at the late embryonic stages, and in taste bud cells and intralingual ganglionic cells which lacked GAP-43-LI. The similarities in distribution patterns of GAP-43-LI and PGP 9.5-LI during the development and mature circumvallate papilla suggest that GAP-43 may be a key neuronal molecule for induction and maintenance of the taste buds.

Senescence-related change in autologous mixed-lymphocyte reaction in senescence-accelerated mice.

Using the senescence-accelerated mouse (SAM) strains, we examined the senescence-related changes of autologous mixed-lymphocyte reaction (AMLR) as well as the phenotypic alteration of the T cell subsets. Splenic T cells from senescence-prone (SAM-P) and resistant (SAM-R) strains of mice were incubated with autologous non-T cells, and AMLR was measured on day 1-5. The kinetics of AMLR responses revealed a marked alteration in senescent SAM-P but not in non-senescent SAM-R mice, in which the peak response occurred at day 1, the response decreasing thereafter up to day 5. Similar senescence-related change was observed in aged (24-month-old) SAM-R and BALB/c mice. Furthermore, the T cells from the aged SAM-R mice cultured with non-senescent syngeneic non-T cells showed a very similar pattern to that cultured with autologous non-T cells. Flow cytometric analysis of T cell phenotype indicated that the percentage of CD4+ CD45RBhi T cells correlated with the peak AMLR responses in both SAM-P and SAM-R mice, and that the percentage of the T cell subset with extrathymic properties was significantly higher in SAM-P mice. These findings suggest that the alteration in kinetics of AMLR is related to senescence but not to the strain of mice, and may reflect a senescence-related dysfunction of the autoregulatory immune mechanisms of T cells.

A flexible dorsal wrist splint.

The authors have used a newly designed dorsal wrist splint on 65 patients since 1989. The splint base is made of Orthoplast. The design has a slender metacarpal bar across the palm, which does not interfere with the motion of the thumb and the normal sensation of the palm and provides some elasticity. The authors explored the conditions under which use of this splint would be appropriate from review of medical charts and the patients' comments. Fifty-five patients have used the splint, three patients could not use it, and another seven patients could not be reviewed about whether they used the splint. Of the 53 patients who could be interviewed in this study, 37 have worn the splint during housework and on the job. The authors believe that patients can perform most activities of daily living and occupations while using the dorsal wrist splint.

Milk of northern fur seal: composition, especially carbohydrate and protein.

The milk of northern fur seal was analyzed with special interest in carbohydrate and protein. High solids (61%) and fat (45.6%) were characteristics of its gross composition. Fatty acid distribution showed that more than 22% of the fatty acids had carbon chains longer than 20 and that approximately 70% contained one or more double bonds. Analysis of free sugars showed no lactose but 123 mg/100 ml of myo-inositol. In carbohydrates bound to casein, .99% of sialic acid and .2% of glucosamine were determined. The amino acid composition of casein showed higher tryptophan, lysine, serine, and glycine than bovine casein, and lower arginine, proline, and leucine. In whey, arginine, threonine, and valine were higher, whereas lysine, aspartic acid, isoleucine, and leucine were lower than in bovine whey. Amino acid patterns in casein and whey were similar to those of cat milk. The appearance of casein micelles was similar to bovine casein micelles. The mean diameter, however, was larger (approximately 330 nm). Electrophoretic pattern of casein showed five major bands in addition to minor components. One of the minor components was a glycoprotein, probably kappa-casein-like protein. The major whey protein had a mobility similar to that of bovine beta-lactoglobulin. No alpha-lactalbumin-like protein was observed.