Observation and determination of periodontal tissue profile using optical coherence tomography.

BACKGROUND AND OBJECTIVE: Diagnosis is a crucial step in periodontal treatment. The aim of this study was to evaluate the effectiveness of optical coherence tomography (OCT) for observation and determination of periodontal tissue profiles in vivo. MATERIAL AND METHODS: In experiment 1, refractive indices of purified water, porcine gingiva and human gingiva at 1330 nm were determined for the analysis of OCT images of periodontal tissues. In experiment 2, OCT examination was performed in the midlabial apico-coronal plane of mandibular anteriors in 30 Asian volunteers with healthy gingiva. Sulcus depth was measured on intra-oral photographs taken during probing. In the OCT images, the gingival, epithelial and connective tissue thickness, and the position of alveolar bone crest were determined and finally, the biologic width was measured. RESULTS: Refractive indices of purified water, porcine gingiva and human gingiva were 1.335, 1.393 and 1.397, respectively. Cross-sectional images of gingival epithelium, connective tissue and alveolar bone were depicted in real-time. The sulcular and junctional epithelium could be visualized occasionally. Laser penetration and reflection were limited to a certain depth with an approximate maximal imaging depth capability of 1.5 mm and OCT images of the periodontal structure were not clear in some cases. The average maximal thickness of gingiva and epithelium and biologic width at the mandibular anteriors were 1.06 ± 0.21, 0.49 ± 0.15 and 2.09 ± 0.60 mm, respectively. CONCLUSION: OCT has promise for non-invasive observation of the periodontal tissue profile in detail and measurement of internal periodontal structures including biologic width in the anterior region.

C-reactive protein to albumin ratio is a prognostic factor for patients with cStage II/III esophageal squamous cell cancer.

C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.

Estimation of the enamel and dentin mineral content from the refractive index.

Recent advances in the field of optics have enabled accurate and localized measurement of optical properties of biological substrates. This work aimed to elucidate the relationship between the local refractive index (n) and mineral content (MC) of enamel and dentin. De- and remineralized lesions in bovine enamel and dentin blocks were sectioned into 300- to 400-µm-thick slices, and placed on a metal plate to capture images of sound, de- and remineralized regions transversely by optical coherence tomography. Mean n at each depth level of the lesion (20- or 40-µm steps for enamel or dentin) was measured by the optical path length-matching method and used to plot n through lesion depth. The specimens were further polished and processed for transverse microradiography for analysis of MC. The n and MC ranged from 1.52 to 1.63 and 50 to 87 (vol.%) in enamel, and from 1.43 to 1.57 and 11 to 48 (vol.%) in dentin, respectively. Strong, positive linear correlations were found between n and MC (Pearson's r = 0.95 and 0.91 for de- and remineralized enamel, and r = 0.94 and 0.91 for dentin, respectively, p < 0.001). Experimental data were validated with a theoretical calculation of n from MC. De- and remineralization of enamel and dentin resulted in measurable changes of n, and, in turn, MC changes of the tissue could be estimated with good accuracy from this long-known optical property by the new analytical approach. Compositional changes of enamel crystallites after remineralization affect n.

Noninvasive cross-sectional imaging of incomplete crown fractures (cracks) using swept-source optical coherence tomography.

AIM: To investigate the ability of swept-source optical coherence tomography (SS-OCT) to detect incomplete crown fractures (cracks) in extracted teeth. METHODOLOGY: Cracks were created by subjecting 30 porcine premolars to impaction by a steel rod plunging from the occlusal tip. SS-OCT images and stereomicroscopic photographs of the surface were acquired for each specimen before and after impaction. For evaluation, the focused light beam of SS-OCT was projected from three directions on the same plane: buccal or lingual, 45° to the mesial, and 45° to the distal. Histological sections were prepared after impaction, and length and width of cracks and lamellae were evaluated using the corresponding SS-OCT image. The values were analysed using Pearson's correlation coefficient. RESULTS: Through SS-OCT, cracks and lamellae were clearly detected as intensified scattering signals at the same position on the corresponding microphotographs and histological sections. Amongst the three scanning angles, the greatest lengths and widths were considered the corresponding values of SS-OCT and were used for analysis. Significant correlations regarding line length and width were observed between SS-OCT and histological sections (length: r = 0.65, P < 0.001; width: r = 0.60, P < 0.001). CONCLUSIONS: SS-OCT can clearly discriminate cracks, which appear as highlighted lines due to the scattering of light. The results obtained from the three scanning directions were correlated well with those of the histological sections.

Framework Implementation of the INSPIRE ICOPE-CARE Program in Collaboration with the World Health Organization (WHO) in the Occitania Region.

INTRODUCTION: Limiting the number of dependent older people in coming years will be a major economic and human challenge. In response, the World Health Organization (WHO) has developed the «Integrated Care for Older People (ICOPE)¼ approach. The aim of the ICOPE program is to enable as many people as possible to age in good health. To reach this objective, the WHO proposes to follow the trajectory of an individual's intrinsic capacity, which is the composite of all their physical and mental capacities and comprised of multiple domains including mobility, cognition, vitality / nutrition, psychological state, vision, hearing. OBJECTIVE: The main objective of the INSPIRE ICOPE-CARE program is to implement, in clinical practice at a large scale, the WHO ICOPE program in the Occitania region, in France, to promote healthy aging and maintain the autonomy of seniors using digital medicine. METHOD: The target population is independent seniors aged 60 years and over. To follow this population, the 6 domains of intrinsic capacity are systematically monitored with pre-established tools proposed by WHO especially STEP 1 which has been adapted in digital form to make remote and large-scale monitoring possible. Two tools were developed: the ICOPE MONITOR, an application, and the BOTFRAIL, a conversational robot. Both are connected to the Gerontopole frailty database. STEP 1 is performed every 4-6 months by professionals or seniors themselves. If a deterioration in one or more domains of intrinsic capacity is identified, an alert is generated by an algorithm which allows health professionals to quickly intervene. The operational implementation of the INSPIRE ICOPE-CARE program in Occitania is done by the network of Territorial Teams of Aging and Prevention of Dependency (ETVPD) which have more than 2,200 members composed of professionals in the medical, medico-social and social sectors. Targeted actions have started to deploy the use of STEP 1 by healthcare professionals (physicians, nurses, pharmacists,…) or different institutions like French National old age insurance fund (CNAV), complementary pension funds (CEDIP), Departmental Council of Haute Garonne, etc. Perspective: The INSPIRE ICOPE-CARE program draws significantly on numeric tools, e-health and digital medicine to facilitate communication and coordination between professionals and seniors. It seeks to screen and monitor 200,000 older people in Occitania region within 3 to 5 years and promote preventive actions. The French Presidential Plan Grand Age aims to largely implement the WHO ICOPE program in France following the experience of the INSPIRE ICOPE-CARE program in Occitania.

Integrated Care for Older People and the Implementation in the INSPIRE Care Cohort.

BACKGROUNDS: The World Health Organization has published the Integrated Care for Older People, ICOPE handbook Guidance on person-centred assessment and pathways in primary care. This is an integrated individual care tool focused on the individual and healthy ageing. The ICOPE tool proposes step by step, a screening, a fine assessment, the development of a personalized care plan, its implementation and follow up and finally the consideration of the caregivers and community. The new Geroscience field is focusing on preventing age-related diseases, and should now investigate with the ICOPE tool the optimal maintenance of intrinsic capacity (IC) through mobility, cognition, psychology, vitality, hearing and vision. This article aims to present this new tool and to presents its innovative implementation at the Toulouse University Hospital through the INSPIRE study. We believe that the ICOPE integrated care program will also be a pragmatic way to maintain cognitive functions and detect early Alzheimer. OBJECTIVES: The main objective of the INSPIRE study is to build a Bio-resource Research Platform for Healthy Ageing gathering biological, clinical and digital resources in order to identify markers of ageing, age-related diseases and IC evolution. The study will be also testing the implementation and follow up of the ICOPE tool. METHODS: The Inspire Platform will gather clinical data and bio-specimens from 1000 subjects in the Occitania Region, of different ages (from 30 years and over) over 10 years. Data will be collected annually. Using the ICOPE tool IC domains will be monitored every 4 months. Once IC decline is identified, participants will have a thorough clinical assessment and blood sampling to investigate the response of markers of ageing at the time of decline. The French ethic committee approved the study. RESULTS: The Inspire platform aims to develop an integrative approach to promote novel new technologies for the assessment and monitoring of functional capacities.

Epithelium-derived chemokines induce airway smooth muscle cell migration.

BACKGROUND: The remodelling of airway smooth muscle (ASM) associated with asthma severity may involve the migration of ASM cells towards the epithelium. However, little is known about the mechanisms of cell migration and the effect of epithelial-derived mediators on this process. OBJECTIVE: The main objective of the current study is to assess the effects of epithelial-derived chemokines on ASM cell migration. METHODS: Normal human ASM cells were incubated with supernatants from cells of the bronchial epithelial cell line BEAS-2B and normal human bronchial epithelial (NHBE) cells. To induce chemokine production, epithelial cells were treated with TNF-alpha. Chemokine expression by epithelial cells was evaluated by quantitative real-time PCR, ELISA and membrane antibody array. To identify the role of individual chemokines in ASM cell migration, we performed migration assays with a modified Boyden chamber using specific neutralizing antibodies to block chemokine effects. RESULTS: Supernatants from BEAS-2B cells treated with TNF-alpha increased ASM cell migration; migration was increased 1.6 and 2.5-fold by supernatant from BEAS-2B cells treated with 10 and 100 ng/mL TNF-alpha, respectively. Protein levels in supernatants and mRNA expression by BEAS-2B cells of regulated on activation, normal T cell expressed and secreted (RANTES) and IL-8 were significantly increased by 100 ng/mL TNF-alpha treatment. The incubation of supernatant with antibodies to RANTES or IL-8 significantly reduced ASM cell migration, and the combined antibodies further inhibited the cell migration. The migratory effects of supernatants and inhibiting effects of RANTES and/or IL-8 were confirmed also using NHBE cells. CONCLUSION: The results show that chemokines from airway epithelial cells cause ASM cell migration and might potentially play a role in the process of airway remodelling in asthma.

Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock.

Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.

Differentiation between superficial and deep lobe parotid tumors by magnetic resonance imaging: usefulness of the parotid duct criterion.

BACKGROUND: The location of a parotid tumor affects the choice of surgery, and there is a risk of damaging the facial nerve during surgery. Thus, differentiation between superficial and deep lobe parotid tumors is important for appropriate surgical planning. PURPOSE: To evaluate the usefulness of using the parotid duct, in addition to the retromandibular vein, for differentiating between superficial and deep lobe parotid tumors on MR images. MATERIAL AND METHODS: Magnetic resonance images of 42 parotid tumors in 40 patients were reviewed to determine whether the tumor was located in the superficial or deep lobe. In each case, the retromandibular vein and the parotid duct were used to locate the tumor. The parotid duct was only used in cases where the tumor and the duct were visualized on the same image. RESULTS: Using the retromandibular vein criterion, 71% of deep lobe and 86% of superficial lobe tumors were correctly diagnosed, providing an accuracy of 81%. However, the accuracy achieved when using the parotid duct criterion was 100%, although it could be applied to only 28 of the 42 cases. Based on these results, we defined the following diagnostic method: the parotid duct criterion is first applied, and for cases in which it cannot be applied, the retromandibular vein criterion is used. The accuracy of this method was 88%, which was better than that achieved using the retromandibular vein criterion alone. CONCLUSION: The parotid duct criterion is useful for determining the location of parotid tumors. Combining the parotid duct criterion with the retromandibular vein criterion might improve the diagnostic accuracy of parotid tumor location compared to using the latter criterion alone.

Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure.

BACKGROUND: Occupational asthma (OA) may cause alterations of airways with inflammation and remodelling after cessation of exposure. Although the long-term clinical, functional and induced sputum sequelae have been examined in workers removed from exposure, the long-term pathological outcomes are unknown. OBJECTIVE: We aimed to investigate whether airway inflammation and remodelling were present in bronchial biopsies of subjects with prior OA but without evidence of persisting asthma at a mean interval of 14 years after cessation of exposure. METHODS: Ten clinically and functionally asymptomatic subjects with a prior diagnosis of OA were recruited and underwent bronchoscopy, bronchoalveolar lavage and bronchial biopsy. Comparisons were made with biopsies from normal control subjects. Epithelial detachment, epithelial metaplasia, mucous gland and airway smooth muscle (ASM) areas as well as the distance between the epithelium and ASM were measured by image analysis. The amount of collagen present was assessed by van Gieson staining. The numbers of TGF-beta1- and eosinophil cationic protein (ECP)-positive cells were evaluated by specific immunostaining. RESULTS: Statistically significant increases were found in the numbers of TGF-beta1- and ECP-positive cells and in the amount of subepithelial fibrosis present in the biopsies of subjects with prior OA compared with control biopsies. The distance between the epithelium and ASM was significantly reduced in the OA group. Increases in epithelial metaplasia, ASM mass, mucous gland numbers, collagen deposition and eosinophilia in the OA group were not statistically significant. There was no evidence of ongoing inflammation in the group with prior OA as assessed by the number of T lymphocytes present. CONCLUSION: Some aspects of airway inflammation and remodelling persist in subjects with prior OA long after cessation of exposure even in the absence of clinical, sputum and functional abnormalities. These findings are relevant to the assessment of long-term sequelae in subjects with OA when reviewed after cessation of exposure.

Repair of osteochondral defects with a new porous synthetic polymer scaffold.

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p<0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.

Real-Time Imaging of Gap Progress during and after Composite Polymerization.

The aims of this study were to observe the behavior of composite and formation of gaps during and immediately after light polymerization using swept source optical coherence tomography (OCT) and to compare the interfacial integrity of adhesives in cavities through 3-dimensional (3D) image analysis. Forty tapered cylindrical cavities (4-mm diameter, 2-mm depth) were prepared in bovine incisors and restored using Bond Force (BF), Scotchbond Universal Adhesive (SBU), OptiBond XTR (XTR), or Clearfil SE Bond 2 (SE2), followed by Estelite Flow Quick flowable composite. Real-time imaging was performed at the center of restoration by the OCT system (laser center wavelength: 1,330 nm; frequency: 30 KHz) during and up to 10 min after light curing. The 3D scanning was performed 0, 1, 3, 5, and 10 min after light curing. The percentages of sealed enamel and dentin interface area (E%, D%) were calculated using Amira software. In real-time videos, the initial gaps appeared as a bright scattered area mainly on dentin floor and rapidly progressed along the cavity floor. The timing, rate, and extent of gap formation were different among the specimens. From 3D visualization, gap progress could be seen on both enamel and dentin even after irradiation; furthermore, typical toroidal gap patterns appeared at the dentin floor of BF and SBU. XTR and SE2 showed nearly perfect sealing performance on the dentin floor up to the 10 min that images were recorded. From quantitative analysis, SE2 and XTR showed significantly higher E% and D% than other groups. SBU showed the smallest E% and BF showed a significantly smaller D% than other groups ( P < 0.05). In conclusion, real-time observation of composite placement and 3D quantification of interfacial gaps were implemented within the experimental limitations. Interfacial gap formation during polymerization of the composite depended on the adhesive system used. The formed gaps continued to propagate after composite light curing finished.

Three-Dimensional Analysis of Enamel Crack Behavior Using Optical Coherence Tomography.

The aim of this study was to nondestructively analyze enamel crack behavior on different areas of teeth using 3D swept source-optical coherence tomography (SS-OCT). Ten freshly extracted human teeth of each type on each arch ( n = 80 teeth) were inspected for enamel crack patterns on functional, contact and nonfunctional, or noncontact areas using 3D SS-OCT. The predominant crack pattern for each location on each specimen was noted and analyzed. The OCT observations were validated by direct observations of sectioned specimens under confocal laser scanning microscopy (CLSM). Cracks appeared as bright lines with SS-OCT, with 3 crack patterns identified: Type I - superficial horizontal cracks; Type II - vertically (occluso-gingival) oriented cracks; and Type III - hybrid or complicated cracks, a combination of a Type I and Type III cracks, which may or may not be confluent with each other. Type II cracks were predominant on noncontacting surfaces of incisors and canines and nonfunctional cusps of posterior teeth. Type I and III cracks were predominant on the contacting surfaces of incisors, cusps of canines, and functional cusps of posterior teeth. Cracks originating from the dental-enamel junction and enamel tufts, crack deflections, and the initiation of new cracks within the enamel (internal cracks) were observed as bright areas. CLSM observations corroborated the SS-OCT findings. We found that crack pattern, tooth type, and the location of the crack on the tooth exhibited a strong correlation. We show that the use of 3D SS-OCT permits for the nondestructive 3D imaging and analysis of enamel crack behavior in whole human teeth in vitro. 3D SS-OCT possesses potential for use in clinical studies for the analysis of enamel crack behavior.

Estimation of whole-body radiation exposure from brachytherapy for oral cancer using a Monte Carlo simulation.

Early stage oral cancer can be cured with oral brachytherapy, but whole-body radiation exposure status has not been previously studied. Recently, the International Commission on Radiological Protection Committee (ICRP) recommended the use of ICRP phantoms to estimate radiation exposure from external and internal radiation sources. In this study, we used a Monte Carlo simulation with ICRP phantoms to estimate whole-body exposure from oral brachytherapy. We used a Particle and Heavy Ion Transport code System (PHITS) to model oral brachytherapy with 192Ir hairpins and 198Au grains and to perform a Monte Carlo simulation on the ICRP adult reference computational phantoms. To confirm the simulations, we also computed local dose distributions from these small sources, and compared them with the results from Oncentra manual Low Dose Rate Treatment Planning (mLDR) software which is used in day-to-day clinical practice. We successfully obtained data on absorbed dose for each organ in males and females. Sex-averaged equivalent doses were 0.547 and 0.710 Sv with 192Ir hairpins and 198Au grains, respectively. Simulation with PHITS was reliable when compared with an alternative computational technique using mLDR software. We concluded that the absorbed dose for each organ and whole-body exposure from oral brachytherapy can be estimated with Monte Carlo simulation using PHITS on ICRP reference phantoms. Effective doses for patients with oral cancer were obtained.

A case of a large retroperitoneal liposarcoma presenting as an incarcerated inguinal hernia.

We report a rare case of retroperitoneal liposarcoma developing within an incarcerated inguinal hernia. A 53-year-old man presented to our hospital with left inguinal mass. Preoperative computed tomography revealed an intraabdominal huge mass, and a clinical diagnosis of liposarcoma. Physical findings except for the inguinal mass and laboratory examination, including tumor markers (CEA, CA19-9), were within normal range. Intraoperatively, the mass was incarcerated in the inguinal canal and involved the left testis. We performed a radical tumor resection, including a left orchiectomy. The resected specimen measured 45 x 30 cm and weighed 7,510 g. Histopathologically, the tumor was diagnosed as a well-differentiated liposarcoma, and originated from retroperitoneum. We did not undergo adjuvant therapy in consideration of histopathological subtype and curable surgical treatment. The patient is well and shows no evidence of recurrence four months after the operation.

Susceptibility of germ-free rats to the hepatotoxic effects of dimethylnitrosamine or dimethylamine plus sodium nitrite administered orally.

The influence of intestinal microflora on the hepatotoxic effects of dimethylnitrosamine (DMN) or dimethylamine (DMA) plus NaNO2 was studied by comparing the degree of liver necrosis and the levels of serum alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) in germ-free and conventional male Wistar rats (320 to 340 g). In one experiment, both germ-free and conventional rats were intubated with DMN in respective doses of 8, 9, and 10 mg/kg of body weight, while in another experiment, both groups were intubated with DMA (1500 mg/kg) plus NaNO2 (100 mg/kg). In both experiments, 48 hr after intubation, there was a marked difference in the degree of liver necrosis and the levels of serum GPT and GOT between the groups. In particular, a dose of 8 mg of DMN or 1500 mg of DMA plus 100 mg of NaNO2 produced severe liver necrosis in the majority of germ-free rats, while the same dose did not produce any detectable liver necrosis in the majority of conventional rats. At a dose of 8 mg, serum GPT and GOT levels were raised to 22 and 15 times normal values, respectively, in germ-free rats, but only to about twice the normal values for both levels in conventional rats. At the combination dose of DMA plus NaNO2, the levels of serum GPT and GOT were raised to 40 and 30 times normal values, respectively, in germ-free rats, while both levels remained almost normal in conventional rats. Thus, the results indicated that the liver of the germ-free state was far more susceptible to the acute toxic effects of DMN as well as DMA plus NaNO2 administration at a certain dose range than was the liver of the conventional state, suggesting the influence of the absence of microflora.

Gastrointestinal carcinogenesis in germ-free rats given N-methyl-N'-nitro-N-nitrosoguanidine in drinking water.

This study was designed to clarify the role of gut microflora in tumorigenesis by a comparison of tumor production between male germ-free and conventional Wistar rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 100 microgram/ml in drinking water. Ninety-one % of conventional MNNG-treated rats that died or were killed by Day 314 of the experiment developed tumors in the gastrointestinal tract, whereas only 17% of germ-free treated rats developed such tumors. In addition, large tumors, some 5 cm or more in diameter, were frequently observed in the conventional rats, whereas only small tumors 0.4 to 1.2 cm in diameter were present in the germ-free rats. Furthermore, multiple tumors including double tumors were often found in the conventional rats, while such tumors never appeared in the germ-free rats. The results suggest that gut microflora might exert a promoting influence on tumorigenesis by MNNG in the gastrointestinal tract. The promoting influence of the microflora in conventional rats might not be of a simple nature, since the influence of a variety of factors modified by the micorflora on tumorigenesis by MNNG p.o. is unavoidable.

Induction of pituitary tumors in germ-free rats exposed to Aspergillus versicolor.

We clarified the role of mold exposure in pituitary tumor induction using 53 germ-free Wistar rats exposed before birth and continually exposed thereafter, to Aspergillus versicolor alone. Rats were autopsied at 540 to 730 days. Untreated germ-free controls were autopsied on day 730. Thirty-three of the 53 monoassociated rats had pituitary tumors (62.3%), while only three of the 41 control germ-free rats had tumors (7.3%). It seems likely that this high incidence of pituitary tumor in the experimental rats is due to metabolites derived from the mold.

Tumor induction in germ-free rats fed bracken (Pteridium aquilinum).

This study indicated that there was no significant difference in the incidence of intestinal tumors between germ-free and conventional rats fed a diet containing bracken, suggesting that gut microflora did not play a definite role in bracken tumorigenesis. However, bracken induced exclusively sarcoma but no adenocarcinoma in germ-free rats, whereas it induced predominantly adenocarcinoma in conventional rats.

Expression of glutaredoxin in human coronary arteries: its potential role in antioxidant protection against atherosclerosis.

Oxidative stress is considered an important factor in atherogenesis. Mammalian cells have a complex network of antioxidants such as catalase, superoxide dismutase, and glutathione peroxidase. However, the mechanisms that regulate the cellular redox state in the vessel wall remain unclear. Recent study has shown that thioredoxin, a thiol-disulfide oxidoreductase, is expressed in atherosclerotic plaques of human carotid arteries. In this study, we investigated the localization and expressional change of glutaredoxin and thioredoxin, two important members of the thiol-disulfide oxidoreductases, in autopsy samples of human coronary arteries. In nonatherosclerotic coronary arteries, glutaredoxin was expressed in endothelial cells, in fibroblasts of the adventitia, and most intensely in medial smooth muscle cells. Interestingly, in atherosclerotic lesions such as hypercellular lesions, the infiltrating macrophages highly expressed glutaredoxin. The expressional pattern of thioredoxin was quite similar to that of glutaredoxin. Western blot analysis demonstrated that hydrogen peroxide stimulated the expression of glutaredoxin in a time- and dose-dependent manner in cultured human coronary artery smooth muscle cells. Fluorescence microtopography with dihydroethidium demonstrated that the generation of reactive oxygen species was associated with the expression of glutaredoxin. These results suggest the possible involvement of thiol-disulfide oxidoreductases in antioxidant protection in human coronary arteries.