CROMAKALIM SUPPRESSES HYPERTONIC SALINE-INDUCED RENAL VASOCONSTRICTION IN ANAESTHETIZED DOGS

1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 μg/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.     

Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption.

Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.     

Immunohistochemical analysis of inducible nitric oxide synthase (iNOS) and heat shock proteins (HSPs) in ameloblastomas

BACKGROUND: To clarify the possible role of nitric oxide (NO) and stress proteins in oncogenesis and cytodifferentiation of odontogenic epithelium. Inducible NO synthase (iNOS) and heat shock proteins (HSPs) were analyzed in ameloblastomas as well as in tooth germs. METHODS: Specimens of seven tooth germs, 36 benign ameloblastomas and five malignant ameloblastomas were examined by immunohistochemistry using antibodies against iNOS and 27-, 60- and 70-kDa HSPs (HSP27, HSP60 and HSP70). RESULTS: Immunoreactivity for iNOS was detected in normal and neoplastic odontogenic epithelial cells and was higher in malignant ameloblastomas than in tooth germs and benign ameloblastomas. HSP27 was expressed constitutively in all odontogenic epithelial cells in tooth germs and benign and malignant ameloblastomas. Expression of HSP60 and HSP70 was detected in normal and neoplastic odontogenic epithelial cells and was prominent in cells neighboring the basement membrane. HSP60 reactivity showed no apparent difference between normal and neoplastic odontogenic epithelium, whereas HSP70 expression was slightly higher in benign and malignant ameloblastomas than in tooth germs. CONCLUSIONS: Activation of iNOS might be associated with malignant potential of epithelial odontogenic tumors. Elevated expression of HSP70 is considered to be involved in neoplastic transformation of odontogenic epithelial cells.     

Successful mitral valve repair for active infective endocarditis accompanied by anorexia nervosa

Infective endocarditis of the mitral area accompanied by anorexia nervosa is extremely rare. A 34-year-old Japanese woman presented with high fever and a heart murmur that had developed over the previous 2-month period. Echocardiography revealed mitral regurgitation and vegetation attached to the anterior mitral leaflet, which had markedly prolapsed to the left atrium. We removed the vegetation with a small part of the anterior mitral leaflet and successfully repaired the mitral valve. The patient showed good recovery, and the mitral regurgitation and left ventricular chamber size had satisfactorily decreased at 2 months after the operation.     

Atrial septal defect repair through limited lateral thoracotomy in children

Objective We have developed a surgical method for atrial septal defect repair through a limited right lateral thoracotomy in which the incision line begins 2 cm caudal from the lower angle of the scapula and ends at the midaxial line, thereby improving patient satisfaction with the cosmetic results of treatment. Methods We performed a retrospective review of 28 patients who underwent isolated atrial septal defect repair through a limited right lateral thoracotomy between January 2002 and August 2004. The mean age and mean body weight at the time of the operation were 85.8 months (range 9–236 months) and 23.0 kg (range 8.0–56.0 kg), respectively. All repaired defects were the ostium secundum type. Results There was no operative or late mortality and no late morbidity after a mean follow-up of 26 months (range 12–41 months). Echocardiography showed no residual shunt in any of the patients. The mean length of the skin incision was 7.8 cm (range 5.0–11.0 cm), and almost all the patients had satisfactory cosmetic results. Conclusion The atrial septal defect repair through a limited right lateral thoracotomy in pediatric patients showed satisfactory surgical results and excellent cosmetic results.     

Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta.

In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations.     

Relationship between the number of steps taken and body mass index for male workers in the metropolitan area]

The present study examined the relationship between number of steps and body mass index (BMI) among male workers in the metropolitan area. The number of subjects were 310 (aged 30-59) and they were studied for seven consecutive days. The number of steps was measured by a pedometer. Energy expenditure was assessed by the activity record method. Energy intake was assessed by a food frequency questionnaire. Height and body weight were examined by a self-administered questionnaire. BMI of 81 subjects (26.1%) was greater than 25 kg/m2. The number of steps was 10,682 +/- 4,365 on working days, and 7,135 +/- 4,536 on holidays. Average energy expenditure in seven days was 2,259 +/- 378 kcal/d. The physical activity level (PAL) was 1.5 +/- 0.1. There was a significant correlation between BMI and the number of steps in a working day (r=-0.188, p<0.01). In addition, there were significant correlations between PAL and daily steps on working days (r=0.301, p<0.001), and on holidays (r=0.296, p<0.001). Subjects were divided into four groups according to the median number of steps on working days and energy intake (I; > or =9,894 steps, <1,901 kcal, II; > or =9,894 steps, > or =1,901 kcal, III; <9,894 steps, <1,901 kcal, IV; <9,894 steps, > or =1,901 kcal). BMI of Group IV (24.7 kg/m2) was significantly higher than that of the other Groups. Group III had the highest proportion of subjects (15.7%) with lifestyle related diseases.     

A Tissue-Engineered Artificial Bile Duct Grown to Resemble The Native Bile Duct

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.