Reduction of cisplatin ototoxicity by fosfomycin in animal model

The protective effect of fosfomycin against cisplatin-induced ototoxicity was studied in rats. Sixty-four Fischer rats were injected intravenously with daily doses of 1, 2, 5, and 10 mg/kg of cisplatin with or without 300 mg/kg of fosfomycin for a varying period from 1 to 10 days. The total dose of 10 mg/kg of cisplatin was given equally in all animals. Inner ear damage appeared to be more reduced histopathologically in animals given both cisplatin and fosfomycin than in animals given cisplatin alone. Similarly, renal damage appeared to be reduced histopathologically and functionally by the combined administration of cisplatin and fosfomycin.     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Devices for facial aesthetic improvement in the treatment of skeletal mandibular protrusion

Some techniques for the treatment of mandibular protrusion with consideration for aesthetic improvement of the face as a whole are described. The aesthetic inferiority complex in the mind of patients with masticatory disorders as the chief complaint should not be underestimated. Three techniques were used in this study; preoperative orthodontic treatment, preservation of the patient's self-image, and maintenance of beautiful relationship between the midfacial line and the nasolabial fold as well as the nasal ala.     

Laparoscopic management of common bile duct stones: transcystic approach and choledochotomy

The purpose of this study was to review our experience with laparoscopic common bile duct (CBD) exploration by the transcystic approach and choledochotomy. We selected the transcystic approach for patients whose CBD stones were less than five in number and smaller than 9 mm in diameter, and whose CBD was less than 15 mm in diameter on cholangiograms. Among 217 patients with CBD stones treated laparoscopically, the transcystic approach was performed successfully in 91 of 104 patients in whom it was attempted (87.5%). The other 126 patients underwent laparoscopic choledochotomy, followed by ductal closure with transcystic drainage in 59, T-tube drainage in 46, primary ductal closure in 19, and choledochoduodenostomy in 1. Choledochotomy was converted to open surgery in only 1 patient. The transcystic approach was associated with shorter hospital stay and less morbidity than choledochotomy. However, choledochotomy also had an acceptably low rate of complications. Bile leaks occurred more frequently in those with primary ductal closure than in those with transcystic drainage or T-tube drainage. Residual stones were found in 2 patients with the transcystic approach and in 10 with choledochotomy. The residual stones were removed through the T-tube tract by choledochoscopy in 7 of these 10 patients. From these results we conclude that laparoscopic management of CBD stones is feasible for almost all patients with CBD stones. It is considered to be safe and effective and has the advantage of being a single-stage procedure. Received: July 7, 2000 / Accepted: October 26, 2000     

Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells

Pluripotent stem cells found in a number of organs are usually in small cell populations. However, under adaptive stimulation, they enter the stage of growth and differentiation to compensate for the loss of differentiated cells. To analyze stem cell potential precisely, the exclusion of other differentiated cells and a clonal assay system are strongly required. In this study, we established a colony-forming assay system for pancreatic stem/progenitor cells in vitro. In this culture condition, they received signals for growth and differentiation, and formed clonal colonies including pancreatic endocrine-lineage cells, such as alpha and beta cells. By combining this culture system with flow cytometric cell sorting, pancreatic stem/progenitor cells will be enriched, and their potential can be analyzed precisely in single cell-based experiments.     

A novel relation of fatty acid with age-related macular degeneration

To evaluate the relation between fatty acids and age-related macular degeneration (ARMD), the fatty acid fractions within the red blood cell (RBC) membrane and plasma of 11 ARMD patients and 10 healthy individuals (controls) were determined and compared. RBC arachidonic acid (AA) and docosahexaenoic acid (DHA) exhibited significantly higher values in the ARMD patients than in the controls. RBC levels of palmitic, palmitoleic, oleic and linoleic acids, however, showed significantly higher values in the controls than in the ARMD patients. No significant variations were observed between the two groups in terms of plasma levels of AA, DHA, palmitic, palmitoleic, oleic and linoleic acids. Our findings indicate that polyunsaturated fatty acids, vulnerable to free radicals and reactive oxygen species, and easily peroxidized, may be related to ARMD induction.     

Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [(11)C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.     

Guided bone regeneration with subperiosteal implants of PTFE and hydroxyapatite physical barriers in rats

Regeneration of periodontal and alveolar ridge defects utilizing membranes is a well-established procedure in reconstructive surgery. Biomaterial characteristics and membrane design employed in guided tissue regeneration (GTR) techniques play an important role in good results. The purpose of this histologic experimental study in rats was to compare the use of two physical barriers in the osteopromotion by using GTR principles in bone defects created in tibias. Fifteen animals divided into 3 groups were used: group I (non-porous polytetrafluoroethylene (PTFE) barrier), group II (coral hydroxyapatite (HA) blocks), and group III (defects that received no physical barrier). Histological examination showed varied amounts of newly formed bone beneath both types of barriers. The non-porous PTFE barrier showed better results than the HA group. The results of this study suggest that bone regeneration can be successfully enhanced by a submerged membrane technique.     

Luminal space enlargement by carbachol in rat parotid intralobular ducts

Carbachol (CCh) enlarges the luminal space in rat parotid intralobular ducts, but the mechanism of their enlargement remains obscure. We investigated the involvement of intracellular calcium ions in the enlargement of luminal space by monitoring the luminal space under optical sectioning in a confocal laser scanning microscope using sulforhodamine B. Carbachol increased the intracellular concentration of calcium ions ([Ca2+]i) and the inside diameter without any change in the outside diameter. Removal of extracellular calcium ions modulated CCh-induced changes in [Ca2+]i to transient, but did not markedly inhibit the CCh-induced increase in the inside diameter. Additional loading of BAPTA (1,2-bis (o-aminophenoxy-ethane-n,n,n',n'-tetraacetic acid) in the duct cells suppressed CCh-induced changes. Diphenylamine-2-carboxylate (DPC), but not cytochalasin D, calmodulin inhibitor or nitric oxide synthase inhibitor profoundly suppressed CCh-induced changes. These results suggest that CCh induces enlargement of the luminal space through the activation of DPC-sensitive channels by the release of calcium ions from the intracellular pool.