Survival of Brånemark System Mk III implants and analysis of risk factors associated with implant failure.

The purpose of this study was to retrospectively investigate the outcomes of Brånemark System Mk III TiUnite/Groovy implants placed in patients at Kobe University Hospital. Various risk factors for implant failure, including mechanical coupling, were investigated by univariate and multivariate analysis. The predictive variables investigated included age, sex, smoking habit, general health, history of radiation therapy, application of a dentomaxillary prosthesis, type of prosthesis, use of alveolar bone augmentation, site of implant insertion, mechanical coupling between implants, and the length and diameter of the implants. Of the 907 implants investigated, only 23 were unsuccessful; the overall survival rate was 96.7%. Increased age, radiation therapy, application of a removable prosthesis or dentomaxillary prosthesis, lack of mechanical coupling between implants, and shorter implants (≤8.5mm) were significant risk factors for implant failure according to univariate analysis (P<0.05). Multivariate analysis identified a significant association (P<0.05) between dental implant failure and a lack of mechanical coupling between implants (odds ratio 6.88) and shorter implants (≤8.5mm) (odds ratio 3.43). The findings of this study demonstrated multivariate relationships between various risk factors and dental implant failure.

Antitumor effects of SMANCS on rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene.

We previously found that a high-molecular-weight anticancer agent, polystyrene-co-maleic acid conjugated neocarzinostatin (SMANCS), in which two chains of styrene/maleic acid copolymer are conjugated to the anticancer protein neocarzinostatin (NCS), accumulated more selectively in tumor tissue than in normal tissue and was more stable than NCS in blood. These results indicate that SMANCS should have less systemic toxicity and a better therapeutic effect than NCS. In this study, the antitumor activity and adverse effects of SMANCS were compared with those of NCS by using rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene. When tumors of rats, that had received 7,12-dimethylbenz[a]anthracene (20 mg/kg, one dose, p.o. in oily formulation), became palpable usually after 4-20 weeks, SMANCS treatment was initiated. Thirty days after i.v. administration of SMANCS (0.1 mg/kg 3 times and 0.3 mg/kg 3 times), tumors had shrunk in 35 of 37 rats (a mean weight was about 10% of control value; or decreased to about 30% of the value of before treatment in tumor weight); tumor size had not changed in 1 rat, and in the remaining 1 rat the tumor had enlarged. Thirty days after i.v. administration of NCS, tumors had shrunk in 8 of 14 rats, but the tumor size was unchanged in 1 rat and was enlarged in 5. In the control group, all tumors had enlarged. Development of new tumors was completely prevented by the administration of SMANCS. Histological examination of sequential slices of tumor revealed clear finding of degeneration and tumor encapsulation at 30 days after initial administration of SMANCS, with an accompanying fatty degeneration, but these effects were not observed for tumors treated with NCS. Although red blood cell counts and hemoglobin amounts decreased significantly in rats receiving NCS, no such effects were apparent in the SMANCS group.

Retrospective study of changes in the sensitivity of the oral mucosa: sagittal split ramus osteotomy (SSRO) versus intraoral vertical ramus osteotomy (IVRO).

We investigated changes in the sensitivity of cutaneous points and the oral mucosa after sagittal split ramus osteotomy (SSRO) and assessed the differences between SSRO and intraoral vertical ramus osteotomy (IVRO). The subjects included in this study were 46 patients with mandibular prognathism who underwent IVRO (88 rami) and 30 patients who underwent SSRO (59 rami). An objective evaluation of the neurosensory status of each patient was completed preoperatively and at 1, 4, 8, 12, and 24 weeks postoperatively. Other variables studied for each patient included sex, age, magnitude of mandibular setback, and amount of blood loss during surgery. We found that a neurosensory recovery occurred earlier in the oral mucosa than at cutaneous points. The number of oral mucosa points showing reduced neurosensory function and neurosensory disturbance after SSRO was significantly higher than after IVRO at 1, 4, and 8 weeks (P<0.05). The nerve recovery observed after SSRO was delayed for a longer period than that noted in our previous study of IVRO. In conclusion, we found changes in sensitivity at cutaneous points and the oral mucosa after SSRO and assessed the differences between SSRO and IVRO.

Hydroxylases involved in vitamin D metabolism are differentially expressed in murine embryonic kidney: application of whole mount in situ hybridization.

In this study we examined the expression of 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) and 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) by RT-PCR and whole mount in situ hybridization using organ culture of kidney taken from mouse embryo. First, the kidneys of mouse embryo at 11.5-17.5 days gestation were cultured in the presence or absence of forskolin and 1,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)]. Forskolin and 1alpha,25-(OH)(2)D(3) induced the expression of 1alpha-hydroxylase and 24-hydroxylase, respectively, in a dose- and time-dependent manner. In the absence of stimulants, the expression of 1alpha-hydroxylase and 24-hydroxylase was detected from days 13.5-17.5 gestation. The expression of vitamin D receptor and megalin was detected from days 13.5 and 11.5, respectively. Next, signals for the expression of either 1alpha-hydroxylase or 24-hydroxylase were detected by whole mount in situ hybridization in kidney explants taken from embryo at 15.5 days gestation after the appropriate stimulation. However, the localization of signals differed between the two enzymes; 1alpha-hydroxylase messenger RNA was expressed in the inner area of the kidney explants, whereas 24-hydroxylase messenger RNA was expressed in the surface area. The expression of both hydroxylases was restricted to the epithelium of developing renal tubules. The pattern of megalin expression was similar to that of 1alpha-hydroxylase expression. To confirm the difference in distribution of 1alpha-hydroxylase and 24-hydroxylase transcripts, the explants were hybridized with probes for both 1alpha-hydroxylase and 24-hydroxylase using double labeling techniques after simultaneous stimulation with forskolin and 1alpha,25-(OH)(2)D(3), resulting in the detection at different locations of positive signals for the two enzymes. These results suggest that the expression of 1alpha-hydroxylase is induced in a distinct epithelium of renal tubules from that of 24-hydroxylase even at the early stage of kidney development before glomerulogenesis.

Selective synthesis of novel cyclic phenylazomethine trimers

Novel cyclic phenylazomethine trimers (CPAs) were synthesized in a one-step dehydration of the 4-aminobenzophenone derivatives in the presence of TiCl(4) or p-toluenesulfonic acid (PTS). The CPAs were isolated in over 90% yield under nondilute conditions. When using TiCl(4) as the dehydration agent, the induction of bulky substituents at the alpha-position of the substrate enhanced the yields of the CPAs. On the other hand, PTS served as an effective catalyst for the synthesis of the phenyl-substituted CPA. This different reactivity between TiCl(4) and PTS depends on the dehydration mechanism being dominated by a kinetic process or thermodynamic one. The obtained CPAs were confirmed by NMR, UV-vis spectra, and MM2 calculation to have only a Z conformation and a nonconjugated structure compared to the linear oligophenylazomethines (OPAs) and the aniline-capped OPAs (OPA's).

Ventricular function and cardiac hypertrophy after coronary thrombolysis with tissue-type plasminogen activator (t-PA) in dogs with coronary artery thrombi.

Subacute prognosis of cardiac function after thrombolysis with a modified tissue-type plasminogen activator (t-PA) YM866 was determined in dogs with coronary artery thromboses induced by injection of a thrombin, fibrinogen and autogenous blood mixture. The left ventricular ejection fraction (LVEF) decreased 30 min after occlusion and had not improved 1 week later. Examination after sacrifice revealed myocardial infarction as well as increases in both the left ventricular myocardial area and heart mass. Occluded coronary arteries reperfused by YM866 (0.1 mg kg(-1) i.v.) treatment 30 min after occlusion, by contrast, had improved LVEF and inhibited myocardial infarction development. In addition, the left ventricular myocardial area and heart mass were significantly reduced compared with the vehicle control group 1 week after administration. Although occluded coronary arteries reperfused by YM866 (0.1 mg kg(-1) i.v.) treatment 3 h after occlusion did not show an improvement in the LVEF or inhibition of myocardial infarction development, the left ventricular myocardial area and heart mass decreased significantly compared with the vehicle control group 1 week after administration. In conclusion, early reperfusion by t-PA treatment 30 min after occlusion improved the ventricular function and cardiac hypertrophy, whereas late reperfusion by t-PA treatment 3 h after occlusion did not improve the ventricular function but did inhibit hypertrophy in dogs with coronary artery thrombi.

Surgical treatment of abdominal aortic aneurysm complicated with chronic disseminated intravascular coagulopathy.

Three cases of disseminated intravascular coagulopathy (DIC) with abdominal aortic aneurysm are presented. All three cases underwent aneurysmectomy after heparin therapy. Two of them died after surgery, but hemorrhagic complications were not responsible for their deaths. One of the three cases tolerated the operation without excessive bleeding and was discharged from the hospital. If surgical therapy is required for abdominal aortic aneurysm with DIC, heparin therapy is recommended to lessen operative bleeding.

[The effects of YM26818: 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea and derivatives on pulmonary surfactant secretion and lung compliance].

To discover a novel compound which has an effect on pulmonary surfactant (PS) secretion, we studied the effects of various compounds on PS secretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of ambroxol, which is known as a PS secretagogue, and a compound we discovered from our compounds library, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea: YM-26818 (the increasing effect on PS in BALF, 34.7% at 50 mg/kg, i.p.). In the surfactant deficient model induced by BAL in guinea pigs, YM-26818 (5 and 10 mg/kg, p.o.) significantly increased the contents of PS in the BAL fluid compared with that of control animals (5 mg/kg: 60.3 +/- 8.0, 10 mg/kg: 59.4 +/- 4.3% increase). Concomitantly by these effects, the recovery of lung compliance was observed in this model (AUC of lung volume, control: 560 +/- 15, YM-26818 5 mg/kg: 898 +/- 51, YM-2681 10 mg/kg: 956 +/- 11 ml.min). These results may indicate that YM-26818 is useful for the therapy of adult respiratory distress syndrome (ARDS) and obstructive pulmonary diseases.

[Change in trigeminal mesencephalic neurons after teeth extraction in guinea pig].

Trigeminal mesencephalic (Mes V) neurons innervating the periodontal mechanoreceptor (PMR) are known to play an important role in controlling the bite force and jaw-movements during mastication. After teeth loss, the PMR disappears due to loss of the periodontal membrane. The present work is a study on whether cell death is induced in the Mes V neurons in association with teeth loss. The upper and lower incisors were extracted on the right side in 5 guinea pigs (extraction group) and the other 5 guinea pigs were kept intact (control group). In the extraction group, the animals were kept alive for 58-119 days after teeth extraction. Serial coronal sections (50 microns thick) were made of the midbrain and pons and stained with cresyl violet. The Mes V neurons were counted on every other section. In the caudal half of the Mes V nucleus, where the neurons innervating the PMR are reported to be located, the number of neurons was less on the right side than on the left side (P < 0.01) in the extraction group, while there was no difference between the right and left sides in the control group. We conclude that teeth extraction can induce cell death in the Mes V neurons innervating the PMR and produce a significant change in the brainstem mechanisms controlling mastication.

Endovascular stent placement of cervical internal carotid artery dissection related to a seat-belt injury: a case report.

OBJECT: The incidence of carotid artery dissection related to blunt injury is very low, but the mortality rate is high. Rapid diagnosis and proper treatments are discussed. CLINICAL PRESENTATION: A 48-year-old woman presented diplopia and pulsating tinnitus of the left ear. An angiography showed a carotid cavernous fistula (CCF) and dissection of the extra-cranial internal carotid artery (ICA). To treat the dissection, a self-expanding endovascular stent was used. She has been followed for 6 years without any event and the ICA is patent. CONCLUSION: Prompt diagnosis without delay and intimate follow-up is the key for the treatment of a carotid injury. Those patients who exhibit cervical bruits and/or seat-belt signs should be examined aggressively. Angioplasty with stents is amenable for patients with traumatic carotid dissections requiring vascular reconstruction in the acute stage.

A new, simple method for measuring mucociliary clearance in guinea-pigs.

Airway mucociliary transport (MCT), which continuously removes inhaled particles and cellular debris from deep in the lung, is impaired in a number of diseases such as bronchitis and asthma. In order to determine the effects of candidate drugs on MCT function in the airway, a new in situ method to measure MCT function was established. MCT function is represented by the distance a gelatin solution containing Evans blue as a marker moves after injection into the trachea. The basal rate of dye transport in non-treated guinea-pigs was 4.4+/-0.2 mm/min. The beta2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently accelerated the basal MCT rate. However, its effect was completely inhibited by pretreatment with the non-selective beta -adrenoceptor antagonist, propranolol (1 mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6+/-0.3 mm/min by SO2 gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2-exposed animals at doses previously shown to accelerate basal MCT rate. This simple method is useful for estimating MCT function in several airway disease models and for examining new drugs designed to improve MCT function in airway diseases.

Removal of extracellular Mg2+ suppresses sulfation of glycoconjugates secreted from rabbit trachea in culture.

The influences of extracellular Ca2+ and Mg2+ concentrations on the basal secretion of glycoconjugates from rabbit trachea in organ culture were examined. Over 80% of the 35S-labeled and [3H]glucosamine-labeled glycoconjugates secreted by the trachea were digested upon incubation with chondroitinase ABC. The basal secretion did not occur in the medium at 4 degrees C, indicating an energy-dependent process. The basal secretion at 37 degrees C of 35S-labeled glycoconjugates was prominently suppressed in Mg(2+)-free Tyrode solution but not in Ca(2+)-free Tyrode solution containing ethyleneglycol bis(2-aminoethylether)tetraacetic acid (EGTA). In contrast, the basal secretion of [3H]glucosamine-labeled glycoconjugates was not affected by the Mg2+ concentration in the medium. The results suggest that extracellular Mg2+ largely contributes to sulfation of glycoconjugates basally secreted from rabbit trachea.

Effect of YM-40461, a novel surfactant secretagogue, on chronic obstructive pulmonary diseases and similar symptoms in guinea pigs.

YM-40461 (1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea, CAS 142912-85-4), is a novel surfactant secretagogue. The effect of YM-40461 on symptoms, e.g. change of airway functions and hypoxemia, were examined using guinea pigs with induced subacute bronchitis. Bronchitic guinea pigs exhibited basal lung resistance (RL) was 0.152 +/- 0.005 cm H2O/ml/s (normal: 0.130 +/- 0.002 cm H2O/ml/s) and basal lung compliance (CL) of 0.455 +/- 0.011 ml/cm H2O (normal: 0.509 +/- 0.009 ml/cm H2O). Although YM-40461 slightly improved the lung resistance in these animals, it improved significantly and dose-dependently the lung compliance (0.468 +/- 0.008 ml/cm H2O for 1 mg/kg, 0.477 +/- 0.008 for 3 mg/kg, 0.490 +/- 0.011 for 10 mg/kg, p < 0.05 at 10 mg/kg) compared to nontreated bronchitic guinea pigs. YM-40461 improved airway functions in bronchitic guinea pigs just as wall as the beta 2-adrenoceptor agonist salbutamol. Additionally, YM-40461 significantly reduced airway hyperreactivity in response to intravenously infused acetylcholine (ACh). Basal PaO2 was 83.1 +/- 0.7 cm H2O in healthy guinea pigs and 71.2 +/- 1.7 cm H2O in bronchitic guinea pigs, indicating hypoxemia. A dose of 10 mg/kg of YM-40461 relieved hypoxemia in these animals with the values returning to 81.8 +/- 1.9 cm H2O (p < 0.05). These results suggest that YM-40461 ameliorates chronic obstructive pulmonary disease (COPD)-like symptoms in bronchitis models due to increased surfactant in the airway.

YM-40461 improves airway clearance in guinea pigs with induced subacute bronchitis.

The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.

YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2-exposed guinea pigs.

The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a dose of 10 mg/kg, p.o. significantly improved surfactant production without affecting mucus secretion. These results show that YM-40461 ameliorates MCT dysfunction caused by SO2 exposure by activation of pulmonary surfactant secretion.

Frequent detection of the human herpesvirus 6-specific genomes in the livers of children with various liver diseases.

This study was performed to investigate the frequency of human herpesvirus 6 (HHV-6) infection of the liver in children with a variety of liver diseases and to evaluate the role of HHV-6 infection in pediatric patients with prolonged non-B non-C hepatitis. Detection of the HHV-6 genomes in liver, in peripheral blood mononuclear cells (PBMC), and in plasma was performed by PCR or by in situ hybridization. Liver biopsy materials from 48 patients, in whom HHV-6 infection was serologically confirmed, were available for PCR analysis. Sequences of the HHV-6B genome were detectable in the livers of 36 of 48 patients (75%). The presence of the genome was not associated with serum transaminase activities. The genome was detectable in PBMC of 22 of 31 (71%) patients tested. In these 31 patients HHV-6 was detected in both the livers and PBMC of 20, was detected in PBMC but not in the livers of 2, was detected in the livers but not in PBMC of 3, and was detected in neither of samples of 6. In situ hybridization of the livers of six patients showed the presence of the HHV-6B genome in the nuclei of hepatocytes. The anti-HHV-6 immunoglobulin M antibody was detectable in 2 of 9 of the non-B non-C hepatitis patients, whereas none of the 22 patients with etiology-defined liver diseases tested positive. Cell-free viral DNA was not detectable in either group of patients. Our results showed that HHV-6B is frequently present in the livers of children with a variety of liver diseases but do not support the assumption that HHV-6B infection of the liver is associated with prolonged non-B non-C hepatitis.