Effect of a tunnel-structured ß-tricalcium phosphate graft material on periodontal regeneration: a pilot study in a canine one-wall intrabony defect model.

BACKGROUND AND OBJECTIVE: Tissue regeneration is affected by the porosity, chemical properties and geometric structure of graft materials. Regeneration of severe periodontal defects, such as one-wall intrabony defects, is difficult because of reduced tissue support, and bone grafts are commonly used in such cases. In the present study, a tunnel-structured ß-tricalcium phosphate (tunnel ß-TCP) graft material designed to stimulate bone formation was fabricated. The objective of this pilot study was to evaluate the effect of this graft material on periodontal regeneration in one-wall intrabony defects in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. First, the mandibular second and third incisors were extracted. Experimental surgery was performed 12 wk after tooth extraction. Bilateral 4 × 8 mm (width × depth) one-wall intrabony defects were created in the mesial side of the mandibular canines. At the experimental sites, the defects were filled with tunnel ß-TCP, whereas the control defects were left empty. Twelve weeks after surgery, qualitative and quantitative histological analyses were performed. RESULTS: There were no signs of clinical inflammation 12 wk after surgery. Coronal extension indicative of new bone formation was higher at the experimental sites than at the control sites, although the differences between both the sites in the newly formed cementum and connective tissue attachment were not significant. Newly formed periodontal ligament and cementum-like tissue were evident along the root surface at the experimental sites. The inner surface of the tunnels was partially resorbed and replaced with new bone. New blood vessels were observed inside the lumens of tunnel ß-TCP. CONCLUSION: Tunnel ß-TCP serves as a scaffold for new bone formation in one-wall intrabony defects.

The dipeptidyl peptidase-4 inhibitor vildagliptin has the capacity to repair ß-cell dysfunction and insulin resistance.

The aim of the present study was to determine whether the dipeptidyl peptidase (DPP)-4 inhibitor could repair pancreatic ß-cell dysfunction and insulin resistance. Ten subjects with type 2 diabetes who had never received DPP-4 inhibitor treatment were enrolled in the study. Just before and 3 months after twice-daily administration of vildagliptin (50 mg tablets), insulin secretion and insulin sensitivity were estimated using 2-compartment model analysis of C-peptide kinetics and insulin-modified minimal model parameters, respectively. The first-phase insulin secretion (CS1) was determined as the sum of the C-peptide secretion rate (CSR) from 0 to 5 min (normal range 6.8-18.5 ng/ml/min). The whole-body insulin sensitivity index (SI) was calculated using a minimal model software program (normal range 2.6-7.6×10(-4)/min/µU/ml). After vildagliptin treatment, reductions in mean (± SE) HbA1c were noted (43.28±1.53 vs. 40.98±1.77 mmol/mol; p=0.019). Vildagliptin treatment increased the area under the curve for the C peptide reactivity (CPR) (AUCCPR; 26.66±5.15 vs. 33.02±6.12 ng/ml · 20 min; p=0.003) and CS1 (0.80±0.20 vs. 1.35±0.38 ng/ml/min; p=0.037) in response to an intravenous glucose load. -Vildagliptin treatment significantly increased SI (0.46±0.27 vs. 1.21±0.48×10(-4)/min/µU/ml; p=0.037). The long-term administration of vildagliptin improved CS1 and Si suggesting that this drug has the capacity to repair impairments in pancreatic ß-cell function and insulin resistance in type 2 diabetes.

Safety evaluation of a milk basic protein fraction.

Milk products are widely consumed by individuals in the US population in the form of fluid milk and milk-derived products and ingredients. Milk is a good source of calcium, which plays a role in maintaining bone health. In addition to calcium, the whey protein fraction of milk contains basic proteins that have been demonstrated to increase bone metabolism and inhibit bone resorption. A specific basic protein fraction in milk (Milk Basic Protein; MBP) was tested in an acute oral toxicity study, teratology study, subchronic oral toxicity study, and reverse mutation assay and no treatment related adverse effects were found. MBP has been evaluated for its use as an ingredient in food and concluded to be safe for its intended use.

Gene expression of 5-fluorouracil metabolic enzymes in hepatocellular carcinoma and non-tumor tissue.

5-fluorouracil (5-FU) is a basic agent used in chemotherapy. The aim of this study is to investigate the gene expression of 5-FU anabolic and catabolic enzymes in hepatocellular carcinoma (HCC) and non-tumor tissue, respectively to increase our knowledge of resistant mechanisms to 5-FU in HCC. The relative mRNA level of orotate phosphoribosyltransferase (OPRT), ribonucleotide reductase (RNR), dihydropyrimidine dehydrogenase (DPD) and target enzyme thymidylate synthase (TS), were analyzed in 30 matched samples of HCC (T) and non-tumor tissue (NT) using quantitative RT-PCR. The expression of OPRT, RNR-M1, RNR-M2 and TS is significantly higher in T compared with in NT (1.3-fold increase, 1.6-fold, 7.1-fold, 1.9-fold, respectively), but that of DPD showed no difference between T and NT. Our results show that HCC should not be treated with 5-FU alone because of its instability in liver.

Copper metabolism after living donor liver transplantation for hepatic failure of Wilson's disease from a gene mutated donor.

There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship. Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation. The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father. The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR. Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene. Serum ceruloplasmin level was sufficient in the donor. The right hepatic lobe graft was transplanted to the recipient. Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion. However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms. We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism. After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient.

A three-month repeated oral administration study of a low viscosity grade of hydroxypropyl methylcellulose in rats.

The toxicity of the lowest viscosity grade of hydroxypropyl methylcellulose (HPMC) that is currently commercially available was investigated by means of a three-month repeated oral administration study in male and female Crj:CD (SD) IGS rats at doses of 505, 1,020 and 2,100 mg/kg/day. Body weights of males and females in the 2,100 mg/kg group were lower than those of the control group on and after day 28 of administration, but the differences were not statistically significant. The degree of suppression of body weight gain in males was higher than that in females. This tendency was similar to the results in other toxicity studies of HPMC that have been reported. Males in the 2,100 mg/kg group showed a tendency (not significant) for decreased food consumption and urine volume. Examinations of general signs, hematology, blood chemistry, ophthalmology, absolute and relative organ weights, autopsy and histopathology revealed only a few, apparently coincidental, statistically significant differences from the control, and no evidence of any dose-dependent changes was found. It was concluded that the lowest viscosity grade of HPMC showed extremely low toxicity under the conditions of this study, as has been found for higher viscosity grades.

Dioxins in bile in relation to those in the human liver and blood.

The levels of 20 dioxin congeners, 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and three coplanar polychlorinated biphenyls (Co-PCBs), in bile were examined in comparison with those in the blood and liver, in 27 autopsy cases. Total-TEQ values were the same in the bile (43.2 +/- 30.9 pg TEQ/g lipid) and blood (43.1 +/- 24.2 pg TEQ/g lipid), and three times higher in the liver (127.8 +/- 57.4 pg TEQ/g lipid). Highly chlorinated PCDDs and PCDFs have a tendency to accumulate in the liver, and their levels in bile and blood were relatively low compared with those in the liver, with 1,2,3,4,6,7,8-heptachlorodibenzofuran having the highest tendency among the 20 congeners. Daily excretion in bile was calculated to be 54 pg TEQ at age 65, by assuming that daily bile secretion is 750 ml and is concentrated 7.5-fold in the gallbladder. The correlation between bile and blood total-TEQ was high, with a correlation coefficient of 0.89 among the 27 autopsy cases. Thus, the regression equation of y = 1.14x - 6.02 will provide us levels in bile (total TEQ per g lipid), knowing the blood total-TEQ level, where x is total-TEQ per g lipid of the blood. Furthermore, accumulation of dioxins was estimated to be 0.99, 0.70 and 1.91 pg TEQ/g lipid/year in bile, blood and liver, respectively.

[Metabolism and urinary excretion of chlorpyrifos in rats].

Urinary metabolites and biological half-life of chlorpyrifos (O, O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate) were investigated. Male Wistar rats weighing 200 g were intraperitoneally injected with chlorpyrifos at a level of 0.2 mmol/kg body weight. Both chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) levels in blood showed maximum values at 5 h post-injection, and then decreased rapidly. Biological half-lives of the blood chlorpyrifos and TCP were estimated to 8.15 and 24.66 h, respectively. Urine was collected for 96 h post-injection and hydrolyzed with 4 N HCl or beta-glucuronidase with sulfatase, and TCP released was determined. Urinary excretion levels of the acid hydrolysis-released TCP and the enzyme hydrolysis-released TCP accounted for 86 and 54% of chlorpyrifos administered, respectively. Urinary excretion levels of alkylphosphate for 96 h post-injection were analyzed. The excretion levels of diethylthiophosphate (DETP) and diethylphosphate (DEP) accounted for 45 and 15% of chlorpyrifos administered, respectively. These results indicate that 1) about half of the chlorpyrifos administered was directly hydrolyzed to DETP and TCP, 2) 10 to 20% was hydrolyzed to DEP and TCP after the oxidation to chlorpyrifos oxon, and 3) about 30% was dealkylated to TCP-phosphate after the oxidation.

[Urinary alkylphosphate levels as an index of exposure to organophosphorus insecticides in pest control operators].

In pest control operations, organophosphorus compounds (OP) have been sprayed as insecticides, blood cholinesterase (ChE) activities and urinary alkylphosphate levels were measured for both OP-sprayers (n = 102) and non-sprayers (n = 35) in pest control companies, and the relationship between the analytical results and spraying conditions was investigated. Plasma ChE activities of the OP-sprayers and of the non-sprayers, as well as blood cell ChE activities of the OP-sprayers, were significantly lower than those of employees of chemical factories who served as controls (n = 103). Urinary alkylphosphates were not detected in the controls at all but were detected in 83% of the sprayers and in 57% of the non-sprayer employees of pest control companies. A significant negative correlation (r = -0.34, n = 137, p less than 0.01) between the plasma ChE activities and urinary total alkylphosphate levels was observed in employees of pest control companies. In the case of the employees whose urinary total alkylphosphate levels were 0.1 mumol/g creatinine or more, the plasma ChE activities were 25% decreased compared to the control group. The OP-sprayers showed significantly higher urinary total alkylphosphate levels than the non-sprayers. The OP-sprayers were further divided into two groups. One was sprayers engaged in both cockroach- or fly-control and termite-control operations (sprayers I, n = 54) and the other was sprayers engaged in only cockroach- or fly-control operations (sprayer II, n = 48).(ABSTRACT TRUNCATED AT 250 WORDS)

[Occupational skin hazards in hairdressers and their etiologic factors--results of mass health examination at health centers].

From 1986 to '88, mass health examinations for skin disorders among hairdressers were performed in 4 Health Centers in Osaka Prefecture. Among 306 female hairdressers examined, the prevalence of skin lesions was 49.0%, consisting of skin lesions of hands and arms alone 22.9%, nail lesion alone 13.7%, and both 12.4%. Characteristic features of the skin lesions were dryness, roughness, thickening of epidermis, redness, hyperkeratinization, scales, desquamation, etc. In the case of nails, thinning, onycholysis, onychoschisis, pitting, transverse grooves and onychorexis were characteristic. The relationship between prevalence of skin disorders and site of lesions to history or category of work was studied. For the prevention of these skin hazards, improved chemicals, equipment, and hygienic education are necessary. Periodical health-checks including participation by a dermatologist, and health supervision should be continued with cooperation between Health Centers and beauty salons, because these businesses are principally small-size enterprises.

Relationship between quadriceps femoris muscle volume and muscle torque after anterior cruciate ligament repair.

This study was performed to obtain evidence regarding bilateral hindrance of motor unit (MU) recruitment in the quadriceps femoris (QF) of patients with anterior cruciate ligament (ACL) reconstruction. The subjects included 70 patients who underwent ACL reconstruction and 35 healthy subjects. To identify the muscle torque per unit volume (MTPUV), the peak torque of each velocity of isokinetic performance was divided by muscle volume of the QF measured by a series of cross-sectional images obtained by magnetic resonance imaging scans. Tests revealed that the mean MTPUV of the uninjured (0.113+/-0.03 N m/cm3 at 60 degrees /s, 0.081+/-0.02 N m/cm3 at 180 degrees /s) and injured sides (0.109+/-0.03 N m/cm3 at 60 degrees /s, 0.079+/-0.023 N m/cm3 at 180 degrees /s) were significantly lower than those of the control group (0.144+/-0.05 N m/cm3 at 60 degrees /s, 0.096+/-0.04 N m/cm3 at 180 degrees /s). Previous studies suggested that MU recruitment in the QF of patients with ACL injury was hindered bilaterally. However, the design of their studies could not provide evidence of bilateral hindrance of MU recruitment in the QF. The results of the present study demonstrated that the MTPUV of both injured and uninjured sides of patients were significantly lower than those of the control group.

Selenium status in workers handling aromatic nitro-amino compounds in a chemical factory.

The selenium status of workers handling aromatic nitro-amino (ANA) compounds was evaluated by measurement of their blood and urinary selenium concentrations and blood glutathione peroxidase (GSH-Px) activities. Forty-seven healthy Japanese male workers (42.7 +/- 12.1 yr) handling ANA compounds routinely in a chemical factory were studied as exposed workers, and 107 nonindustrial healthy Japanese males (39.3 +/- 10.0 yr) in the same region served as a control group. Urinary diazoreaction-positive metabolites and methemoglobin, both of which have been used as indices of exposure to ANA compounds, were significantly elevated in the exposed workers. Both plasma and erythrocyte selenium in the exposed workers showed 20% lower values compared to the control group. GSH-Px activities in plasma and erythrocytes were also significantly decreased in the exposed workers, but urinary selenium excretions were similar between the two groups. Questionnaire information obtained from each subject regarding intake habits of selenium-rich foods (bread, eggs, meat, and fish) indicated that the average dietary selenium intake was similar for the control group and the exposed workers. These results indicate that (1) the workers handling ANA compounds were surely exposed to these chemicals; (2) their selenium status was lower than that of the nonindustrial controls; and (3) the low selenium status was not associated with any dietary factor.

Expression of cellular adhesion regulatory molecule in hepatocellular carcinoma.

Cellular adhesion regulatory molecule (CMAR) enhances the adhesiveness of cells to collagen and laminin and is considered to be a candidate anti-oncogene. The purpose of the present study was to investigate the relationship between the expression of CMAR and clinical features of hepatocellular carcinoma (HCC). Small amounts of liver tissue were obtained from HCC and non-cancerous portions of the liver in 29 patients and from normal liver in seven patients with metastatic liver tumour by biopsy under ultrasound guidance. RNA was extracted with acid guanidinium thiocyanate-phenol-chloroform. Expression of CMAR was assessed by quantitative PCR using beta-actin as an internal standard. A 4 b.p. insertion polymorphism at nucleotide 241 of the CMAR coding region was then investigated using extracted RNA to assess the relationship between the expression of variant mRNA of CMAR and HCC carcinogenesis. The relative expression of CMAR was significantly reduced in HCC compared with non-cancerous and normal livers and had a relationship with certain clinical background factors. The reduced expression of CMAR was thought to be closely associated with the progression of HCC. However, the 4 b.p. insertion polymorphism pattern of CMAR was the same between HCC and non-cancerous liver in all cases in which it was found. These results suggest that progression of HCC may be predicted based on the relative expression of CMAR.

[Relationship between exposure to chlorpyrifos and concentration of urinary alkylphosphates in termite control workers].

Chlorpyrifos (O, O-diethyl-3,5,6-trichloro-2-pyridinyl phosphorothioate; CP) has been used for insecticide to prevent infestation of termites. A study was made on occupational exposure to CP of termite control workers engaged in spraying this organophosphorus insecticide. Workers were engaged in two types of spraying; that is spraying CP under floor and spraying CP around house. All the under-floor sprayers wore respirators during spraying. CP levels in air near the breathing zone, contact amounts of CP with skin, and urinary alkylphosphates levels were higher in the under-floor sprayers than in the around-house sprayers. The personal ambient CP levels of the under-floor sprayers were 0.012 to 0.145 (8 h-TWA, mg/m3) lower than the threshold limit value (0.2 mg/m3) proposed by ACGIH. A maximum diethylphosphate (DEP) excretion was observed in the first urine collected the next day, while the highest diethylthiophosphate (DETP) was excreted in the last urine in the working day. In the excretion amount, DEP was higher than DETP. Amounts of CP collected in respirators used by the under-floor spraymen averaged 0.76 mg/respiratory comparable to their estimated theoretical value of 0.69 mg/m3. The urinary total alkylphosphate (DEP + DETP) level was more closely correlated with the contact amount of CP with skin (r = 0.86) than with the personal ambient CP level (r = 0.05). These results indicate that 1) respiratory absorption of CP was prevented by the use of respirator; 2) the urinary alkylphosphates were mainly derived from the dermal absorption of CP; and 3) biological monitoring using urinary alkylphosphates levels is an useful index for CP exposure.

[A questionnaire study on health of taxi drivers--relations to work conditions and daily life].

A questionnaire survey was conducted on 5,523 taxi drivers in Osaka Prefecture to investigate their working conditions and daily life as well as characteristics of their health condition and various effects on health, especially on their cardiovascular system. The major results of this survey were as follows: 1) The rate of subjective symptoms, morbidity rate and rate of poor physical condition over the past year in the taxi drivers were higher than those of the control group. Among the subjective symptoms, the rate of gastrointestinal disorders, fatigue, musculoskeletal system disorders, sensory system disorders, hemorrhoids, etc. was especially high. 2) Work shift, density of work, years of experience in taxi-driving, frequency of fright while driving, pattern of taking meals, way of recuperation on rest days or holidays, obesity, smoking, and intake of coffee and alcohol were found to be factors affecting the health of taxi drivers. 3) Nearly half of the respondents said that they would like to quit or change their job with as much as 62% giving "condition of health" as reason. On the other hand, the rate of heart-related symptoms such as palpitation, and breathlessness did not differ from that of the control group. The possible reason for this deduced from the foregoing results, is that there were some who had changed or quit the job at an early stage for health reasons such as heart trouble and severe physical and mental burden resulting from taxi driving. 4) Many taxi driver are obese and the rate of those with heart-related symptoms was considerably high among those classified as obese. In addition, the results showed that those with longer driving experience tended to be obese.

Selective occlusion with fibrin glue under fistuloscopy: seven cases of postoperative management for intractable complex fistulas.

BACKGROUND AND STUDY AIM: Fistula occlusion is not achieved in some fistulas with complex branches. To obtain early fistula closure in such cases, we insert a double-lumen catheter into each fistula branch, with the aid of a guide wire positioned using a small-caliber endoscope, and attempt selective infusion of fibrin glue. PATIENTS AND METHODS: Following removal of foreign bodies and necrotic granulation, we applied the selective occlusion method under fistuloscopic control to seven intractable external fistulas with complex branches, in which fistula closure had not been obtained by a simple occlusion method (SOM). All the fistulas were complex with more than two branches. RESULTS: Fistula occlusion was obtained within 2 weeks in six of the seven patients, and there has been no sign of recurrence over a follow-up period of 4 - 59 months (average 29.8 months). CONCLUSION: Selective occlusion under fistuloscopy is highly effective for intractable external fistulas with complex branches.

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice.

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.