Adverse effect of dentine bonding agent on the oral mucosa of guinea pigs.

The purpose of present study was to determine the possibility of nebulous discoloration of the oral mucosa of guinea pigs as a result of the application of dentine bonding agents. The materials used were the Clearfil Photo Bond (CPB) system's mixture agent, universal agent and catalyst agent. Four types of experimental catalysts were used. In male albino guinea pigs weighing 300-500 g, oral mucosa irritation tests were performed in accordance with the guidelines of the Cosmetic, Toiletry and Fragrance Association (CTFA). Macroscopical findings on the oral mucosa showed that there was strong nebulous discoloration immediately after application of CPB mix and CPB catalyst and throughout the experimental periods. However, CPB without 10-methacryloxdecyl dihydrogen phosphate (MDP) did not produce noticeable nebulous discoloration and inflammation. The CPB mix caused pathological changes, such as paraketosis and hyperkeratosis on the endepidermis of the mucosa, immediately after its application.

[Baeyer-Villiger reaction of benzaldehydes possessing oxygen functions with SeO2-H2O2].

The Baeyer-Villiger (B. V.) reaction using SeO2-H2O2 was examined for various benzaldehydes possessing methoxy groups and/or a furan ring. When benzaldehydes have an electron-donating group (methoxy group) at the ortho or para position to a formyl group, the B. V. reaction proceeded rapidly and in a good yield. Since the reaction using SeO2-H2O2 is carried out under a neutral condition, this reaction are applicable to aldehyde derivatives with a furan ring which is unstable against acid.

Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21waf1.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cell proliferation and migration. Recently, tranilast, an anti-allergic drug, has been used for the prevention of restenosis after PTCA. To determine the molecular mechanism involved, the effect of tranilast on the proliferation of human coronary smooth muscle cells (SMCs) was investigated. Tranilast arrested the proliferation of human coronary SMCs at the G0/G1 phase of the cell cycle. In association with this inhibitory effect, tranilast increased p21waf1 and p53 tumor suppressor factor, and decreased cyclin-dependent kinase 2 (CDK2) activity. These results suggest that tranilast inhibits the proliferation of human coronary SMCs during restenosis after PTCA via an induction of p21waf1 and p53. Tranilast may thus allow us to prevent restenosis after PTCA by interfering with this mechanism.

Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody.

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value.

Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy. A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy.

Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.

The adverse effect of commercial dentine-bonding systems on the skin of guinea pigs.

It was widely known that 2-hydroxyethyl methacrylate (2-HEMA) can cause contact dermatitis. Commercially available dentine primers and dentine bonding agents that contain 2-HEMA are widely used. The purpose of this study was to investigate the cumulative irritation and delayed hypersensitivity caused by commercial dentine bonding systems when applied to the skin of guinea pigs. We have concluded that almost no dentine bonding systems cause cumulative irritation, but some commercially available dentine bonding systems may produce delayed hypersensitivity.

Advanced glycation end products-driven angiogenesis in vitro. Induction of the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor.

This study was undertaken to determine whether and how advanced glycation end products (AGE), senescent macroproteins accumulated in various tissues under hyperglycemic states, cause angiogenesis, the principal vascular derangement in diabetic microangiopathy. We first prepared AGE-bovine serum albumin (BSA) and anti-AGE antiserum using AGE-RNase A. Then AGE-BSA was administered to human skin microvascular endothelial cells in culture, and their growth was examined. The AGE-BSA, but not nonglycated BSA, was found to induce a statistically significant increase in the number of viable endothelial cells as well as their synthesis of DNA. The increase in DNA synthesis by AGE-BSA was abolished by anti-AGE antibodies. AGE-BSA also stimulated the tube formation of endothelial cells on Matrigel. We obtained the following evidence that it is vascular endothelial growth factor (VEGF) that mainly mediates the angiogenic activities of AGE. (1) Quantitative reverse transcription-polymerase chain reaction analysis of poly(A)+ RNA from microvascular endothelial cells revealed that AGE-BSA up-regulated the levels of mRNAs for the secretory forms of VEGF in time- and dose-dependent manners, while endothelial cell expression of the genes encoding the two VEGF receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase 1, remained unchanged by the AGE treatment. Immunoprecipitation analysis revealed that AGE-BSA did increase de novo synthesis of VEGF. (2) Monoclonal antibody against human VEGF completely neutralized both the AGE-induced DNA synthesis and tube formation of the endothelial cells. The results suggest that AGE can elicit angiogenesis through the induction of autocrine vascular VEGF, thereby playing an active part in the development and progression of diabetic microangiopathies.

Evaluation of skin irritation and sensitization of two diol solutions used as experimental dentin primers in humans and guinea pigs.

The purpose of the present study was to evaluate the safety of ethylene glyco (EG) and 1,6-hexanediol (HD) solutions as experimental dentin primers when subjected to the guinea pig maximization test (GPMT), primary irritation test, cumulative skin irritation test and human patch test. No primary and cumulative skin irritation resulting from the use of 62.5% EG or 45% HD solutions was observed. In the case of GPMT, the animals sensitized with 2-hydroxyethyl methacrylate (2-HEMA) responded to 100% HD. 62.5% EG and 45% HD as dentin primers were safer than 2-HEMA such as a methacrylic primer.

Radioimmunoscintigraphy using technetium-99m-labeled parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen in athymic nude mice bearing tumor.

Biodistribution and imaging characteristics of Tc-99m-labeled parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, were evaluated in athymic nude mice bearing the human CEA-producing gastric carcinoma (MKN-45) xenografts. Group F monoclonal antibodies such as F11-39 and ChF11-39 have been found to recognize the protein epitopes present on the domain B3 of the CEA molecule and to discriminate CEA in tumor tissues from the CEA-related antigens. The Tc-99m labeling was performed by immediately mixing a reduced antibody by 2-mercaptoethanol with Tc-99m pertechnetate in the presence of stannous chloride. The labeling yields of the two antibodies were greater than 95% when estimated using gel chromatography. Although these Tc-99m-labeled antibodies were stable in neutral saline solution, Tc-99m from both labeled antibodies was associated with cysteine solution. Technetium-99m ChF11-39 was more susceptible to transchelation than was Tc-99m F11-39. The immunoreactivity of each Tc-99m-labeled antibody was confirmed using MKN-45 cell-binding assay. Biodistribution studies in tumor-bearing mice were performed at 1 h, 5 h, and 20 h after being given IV injections of 3.7 MBq of either Tc-99m F11-39 or Tc-99m ChF11-39. All tumor-to-organ uptake ratios increased with time for both Tc-99m-labeled antibodies. Imaging results also showed selective and progressive accumulation of both Tc-99m antibodies at the tumor site. Both these Tc-99m-labeled antibodies have proved to be good radiotracers giving satisfactory scintigrams of the CEA-producing tumor.

Contact dermatitis caused by 2-HEMA and GM dentin primer solutions applied to guinea pigs and humans.

The purposes of this study were to examine whether 2-HEMA, GM, and methacrylic acid cause contact dermatitis, and to determine the optimum concentrations of these primers for sensitization and challenge in guinea pigs. A sensitizing concentration of 0.2% 2-HEMA resulted in strong rubefaction and several vesiculopapules in response to the challenge, and a sensitizing concentration of 0.5% GM produced strong rubefaction at 24 hours. We also observed the development of contact dermatitis on human brachia in a closed-patch test. Skin that was treated with both 2-HEMA and GM clearly showed the onset of rubefaction and itchiness. 2-HEMA caused sensitized delayed allergic reactions at all the concentrations tested.

In vitro properties and in vivo behavior of technetium-99m labeled fibrinogens.

Fibrinogen was labeled with Tc-99m by two methods and in vitro stability and the in vivo behavior in mice were studied. The Tc-99m labeling was performed by mixing an unreduced fibrinogen (UnFib) or a reduced fibrinogen (ReFib) with Tc-99m pertechnetate in the presence of stannous chloride. In both of them, chelation with Tc-99m resulted in a single radiochemical product. For the in vitro stability studies, Tc-99m labeled fibrinogen (Tc-99m UnFib) was prepared with UnFib, and transchelation with cysteine solution was easy to produce compared to Tc-99m labeled fibrinogen (Tc-99m ReFib) prepared with ReFib. The radioactivity bound to clottable protein for Tc-99m UnFib and Tc-99m ReFib was about 70% and about 69%, respectively. The in vivo behavior of these labeled fibrinogens was studied, and their efficiencies for imaging an abscess and Ehrlich tumor in mice were determined with a gamma camera. Technetium-99m UnFib underwent a rapid partial exchange of the Tc-99m with compounds of the blood buffer system in vivo, resulting in early biologically active and would be incorporated into the abscess and tumor. The uptake in the abscess increased slightly over time with Tc-99m ReFib, but the abscess to blood and abscess to muscle ratios were 0.09 and 2.6 at 5 hr, respectively. Clearly delineated images of abscess were obtained beginning at about 5 hr after injection. The tumor to blood and tumor to muscle ratios were 0.05 and 1.4 at 5 hr, respectively. The Ehrlich tumor image in mice was slightly visible at 10 hr. The short half-life of Tc-99m was inappropriate for fibrinogen with a low pharmacokinetic value, because it was necessary for imaging of the abscess and tumor to take a long time.

Peak oxygen uptake and respiratory function in persons with spinal cord injury.

This study investigated the association between peak oxygen uptake (peak VO2) during arm cranking exercise and respiratory function in paraplegics. Fourteen male paraplegics were recruited for the present study. The subjects were grouped according to the level of injury into the HL (Th3-Th8) and LL (Th11-L3) group. Prior to the maximal test, pulmonary function, including vital capacity (VC) and residual volume (RV), was measured in the sitting position. Mean peak VO2 in the LL group (1662 ml.min-1) was significantly greater than that in the HL group (1357 ml.min-1), corresponding to 82% of that in the LL group (P < or = 0.05). In respiratory function, the HL group showed marked restrictive impairment of ventilatory function. That is, VC and RV were significantly lower in the HL group than in the LL group (P < or = 0.05). The reduction in VC and RV is related to the degree of loss of control in respiratory functioning muscle mass. However, there was no clear-cut correlation between respiratory function and peak VO2 expressed as a function of body mass (ml.kg-1.min-1). In addition, a multiple linear regression analysis revealed that RV and VC were not associated with peak VO2 (ml.min-1) in contrast to the importance of body mass. It seems reasonable to conclude from these results that respiratory function is not an important factor in determining peak VO2 in the paraplegic.

[Hydrostatic weighing, skinfold thickness, body mass index relationships in high school girls].

A study was conducted to evaluate body composition by hydrostatic weighing, skinfold thickness, and body mass index (BMI) in 102 senior high school girls, aged 15 to 18 in Nagasaki City. Body density measured by the underwater weighing method, was used to determine the fat weight (Fat) and lean body mass (LBM. or fat free weight: FFW) utilizing the formulas by Brozek et al. The results were as follows; 1. Mean values of body density were 1.04428 in the first grade girls, 1.04182 in the second grade, and 1.04185 in the third grade. 2. Mean values of percentage body fat (%Fat) were 23.5% in the first grade, 24.5% in the second and 24.5% in the third. 3. Percentage body fat (%Fat), lean body mass (LBM) and LBM/Height were not significantly with different advance of grade from the first to the third. 4. The correlation coefficients between percent body fat and the sum of two skinfold thicknesses, the sum of three skinfold thicknesses and the sum of seven skinfold thicknesses was 0.78, 0.79, and 0.80 respectively and were all statistically significant (p < 0.001). 5. The correlation coefficients between BMI and the sum of two skinfold thicknesses, the sum of three skinfold thicknesses and the sum of seven skinfold thicknesses was 0.74, 0.74, and 0.74 respectively and were all statistically significant (p < 0.001). 6. Mean values of BMI, Rohrer index and waist-hip ratio (WHR) in all subjects (n = 102) were 20.3, 128.2 and 0.72 respectively.

[Body density assessment utilizing skinfold thickness and age in Japanese men].

A study was conducted to investigate the validity of skinfold-based prediction equations for body density (g/ml) by Nagamine and Suzuki (1964), and to formulate more convenient and more useful equations for predicting body density from skinfold and age in men. Subjects of the study were 257 healthy men aged 19-60 years in or near Nagasaki City. The regression equation for the dependent variable, body density, was determined by hydrostatic weighing. Independent variables included eight skinfolds, the sum of two skinfolds (triceps, subscapular), the sum of three skinfolds (triceps, subscapular, and abdominal), age, and body surface area. Skinfolds were measured with an Eiken-model skinfold caliper. Age (mean 33.1, range 19-60 yrs.), weight (mean 65.3, range 46.6-107.7 kg), height (mean 168.8, range 152.3-185.4 cm), and body density (mean 1.05874, range 1.00860-1.09020 g/ml) were also recorded. Percent body fat was calculated using the formula by Brozek et al. and ranged from 6.1% to 38.9%. Multiple correlation coefficients (MR) and standard error (SE) of 10 regression equations (A-J) for predicting body density in men were obtained. The best-fitting and the most convenient prediction equation for body density was equation-E.: body density = 1.09556-0.00062 x sum of three skinfolds (mm)-0.00028 x age (MR = 0.815 and SE = 0.0087 g/ml). The equation was cross-validated on a different sample of 45 men. The correlation coefficient between predicted and hydrostatically determined body density was 0.781 (p < 0.001). Equation-E (Tahara's equation) appears to be useful in body density analysis particularly when the subjects are Japanese men, aged 18-50 yrs, with percent body fat 10 to 30%.

A delayed hypersensitivity reaction to dentine primer in the guinea-pig.

OBJECTIVE: This study was undertaken to examine the possibility of a delayed hypersensitivity reaction or contact dermatitis occurring in the guinea-pig in response to methacrylate derivatives used as experimental dentine primers. METHODS: The dentine primers 2-HEMA, GM, MA and MMA were tested in a guinea-pig maximization test. RESULTS: All the dentine primers tested produced positive delayed hypersensitivity reactions in the guinea-pig. MMA produced the most severe reaction. CONCLUSION: It is concluded that in the clinical situation, clinicians and other members of the dental team should be aware of the need for careful handling of the dentine primers tested.

[Body density assessment utilizing skinfold thickness and age in Japanese women].

A study was conducted to investigate the validity of skinfold-based prediction equations for body density (g/ml) by Nagamine and Suzuki (1964), and to formulate more convenient and more useful equations for predicting body density from skinfold and age in women. Subjects of the study were 512 healthy women aged 18-66 years in or near Nagasaki City. The dependent variable in the multiple regression equation, body density, was determined by hydrostatic weighing. Independent variables included eight skinfolds, the sum of two skinfolds (triceps, subscapular), the sum of three skinfolds (triceps, subscapular, and abdominal), age, and body surface area. Skinfolds were measured with an Eiken-model skinfold caliper. Age (mean 30.1, range 18-66 yrs.), weight (mean 52.6, range 38.0-83.3 kg), height (mean 157.0, range 142.0-172.0 cm), and body density, (mean 1.04125, range 0.98806-1.08650 g/ml) were also recorded. Percent body fat was calculated using the formula by Brozek et al. and ranged from 6.4% to 48.3%. Multiple correlation coefficients (MR) and standard error (SE) of 10 regression equations (A-J) for predicting body density in women were compared. The best-fitting and the most convenient prediction equation for body density was equation-E. The regression equation developed for predicting body density was: body density = 1.07931-0.00059 x sum of three skinfolds(mm)-0.00015 x age (MR = 0.77 and SE = 0.0089). The equation was cross-validated on a different sample of 46 women. The correlation coefficient between predicted and hydrostatically determined body density was 0.813 (p < 0.001). Equation-E (Tahara's equation) appears to be useful in body density analysis particularly when the subjects are Japanese women, aged 18-50 yrs, with percent body fat 17 to 34%.

In vitro insulinotropic action of a new non-sulfonylurea hypoglycemic agent, calcium (2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), in rat pancreatic B-cells.

We examined the in vitro insulinotropic action of a novel non-sulfonylurea compound, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), which is a succinate derivative, using rat pancreatic islets and perfused pancreas. The sodium salt of KAD-1229 free acid (KAD-1229-Na) stimulated insulin secretion from isolated rat islets and perfused rat pancreas in a concentration-dependent manner at 0.1 to 10 microM. It produced a predominant first phase and a less prominent second phase response in the presence of 5.55 mM glucose. An ATP-sensitive K+ (K+ATP) channel activator, diazoxide, eliminated the insulinotropic effect of KAD-1229-Na. Glucose primed the B-cell in the perfused pancreas, but KAD-1229-Na did not. When the insulinotropic effects of 16.7 mM glucose on isolated rat islets were inhibited submaximally by 1 microM norepinephrine, the addition of 1 microM KAD-1229-Na reversed this inhibition. All of these insulinotropic effects of KAD-1229-Na were qualitatively indistinguishable from those of sulfonylurea compounds. We conclude that KAD-1229-Na acts on K+ATP channels of pancreatic B-cells despite its non-sulfonylurea structure.

[Sex differences in interrelationships between percent body fat (%fat) and waist-to-hip ratio (WHR) in healthy male and female adults].

The purpose of the present study was to investigate sexual differences in relationships among percent body fat (%Fat), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), abdominal circumference to stature ratio (ASR), body mass index (BMI) and skinfold thicknesses in healthy male and female adults. Subjects were 64 males and 65 females, aged 22-60. Body density was measured by under water weighing and by skinfold anthropometry. Mean %Fat was 15.6% in males and 23.9% in females. Mean WHR was 0.83 in males and 0.72 in females. The correlation between %Fat and WHR was not significant in females (r = -0.104) but was significant in males (r = 0.631, p < 0.001). Highly significant correlations were obtained among %Fat, WSR, ASR, BMI, and sum of eight skinfolds in both sexes.

Mental and physical health of middle-aged and elderly women and psychosocial factors.

Middle-aged and elderly women with no specific disabilities in their daily life were divided into two groups: those visiting clinics with mild physical symptoms and those not visiting clinics. Those visiting clinics showed significantly lower mental and physical health indices, but satisfaction and emotional support were similar. Although those visiting clinics had significantly more stressful events, no differences were seen in ways they were dealt with. For those not visiting clinics, mental and physical health indices were better in their 60s than in their 50s and got worse again in their 70s, while for those visiting clinics indices were consistently low. Somatic symptoms in the women visiting clinics could be somatic reactions to their life situation from their 50s to their 60s.

[Body composition (densitometry-hydrostatics), skinfold thickness, BMI and their relationships in junior high school girls].

A study was conducted to evaluate body composition (Hydrostatics = Under-Water Weighing), skinfold thickness, and BMI in 97 junior high school girls, aged 12 to 15, in Nagasaki City. Body density was measured by under-water weighing, and the two compartments--fat weight (Fat) and lean body mass (LBM, or fat free weight: FFW)--were calculated using the formulas of Brozek et al. The results were as follows; 1. Mean values of body density were 1.0501 in first grade girls, 1.0476 in the second grade, and 1.0466 in the third grade. 2. Mean values of percentage body fat (% Fat) were 21.1% in the first grade, 22.1% in the second and 22.5% in the third. 3. Lean body mass (LBM) and LBM/Height increased significantly with advance from the first to the third grade. 4. The correlation coefficient between percent body fat and the sum of two skinfold thicknesses, the sum of three skinfold thicknesses, or the sum of seven skinfold thicknesses were 0.81, 0.80, and 0.82 respectively and all statistically significant (p < 0.001). 5. The correlation coefficient between BMI and the sum of two skinfold thicknesses, the sum of three skinfold thicknesses (r = 0.841) or the sum of seven skinfold thicknesses were 0.85, 0.84, and 0.84 respectively, and all statistically significant (p < 0.001). 6. Mean values of BMI, WSR, ASR, and WHR in all subjects (n = 97) were 19.6, 0.72, 0.39 and 0.43 respectively.