A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion.

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.

Influence of glycerol-induced acute renal failure on the pharmacokinetics of cyclosporin in rats.

Although it is widely believed that renal dysfunction has no effect on the pharmacokinetics of cyclosporin, many clinical reports suggest that renal dysfunction after renal transplantation is closely related to the pharmacokinetics of cyclosporin. To clarify the relationship between renal dysfunction and the pharmacokinetics of cyclosporin, we examined the influence of acute renal failure (ARF) on its pharmacokinetics in glycerol-induced ARF rats. The values of indicators of renal function (serum creatinine, blood urea nitrogen), but not those of indicators of hepatic function, were significantly increased in ARF rats that received glycerol compared with values for control rats. The area under the blood cyclosporin concentration-time curve after oral administration (AUCpo) were 4.976+/-0.847 mghL(-1) for ARF rats and 9.684+/-1.100 mghL(-1) for control rats; AUCpo in ARF was significantly reduced in a manner dependent on renal function. The oral clearance of cyclosporin in ARF and control rats was 1.172+/-0.207 and 0.544+/-0.062Lh(-1) kg(-1), respectively, whereas total body clearance in ARF and control rats was 0.151+/-0.008 and 0.183+/-0.010Lh(-1)kg(-1), respectively. The relative bioavailability of cyclosporin in ARF and control rats was 0.118 and 0.336, respectively. In an in-vitro study using everted sac and liver-slice methods, the apparent first-order rate constants for cyclosporin uptake (k(uptake)) and metabolism (k(metab)) in gut tissues were reduced, whereas k(uptake) and k(metab) in liver were increased. Gastric emptying, measured by use of paracetamol, was significantly reduced in ARF rats. These results suggest that glycerol-induced ARF results in several changes in the pharmacokinetics of cyclosporin in rats. From these results, we conclude that reduction of the absorbed fraction of cyclosporin strongly contributes to the decrease in AUCpo in the presence of ARF.

Severe visual disturbance after exposure of the optic canal during intranasal ethmosphenoidectomy.

The cause of disturbed visual acuity associated with intranasal ethmosphenoidectomy is, on the one hand, a direct injury to the optic nerve. In this case, the disturbance in visual acuity develops immediately after the operation, and severe visual complications with a poor prognosis are found. On the other hand, in the two cases presented in this paper, the disturbed visual acuity develops postoperatively. In this case, it is necessary to take various possibilities into consideration, such as indirect effects of intraorbital bleeding, and damage to the lamina papyracea due to indirect and direct injury. Moreover, effects on the peri-optic nerve area and small blood vessels within the osseous optic canal should be considered. After thorough consideration and observation of the response to conservative therapy, such complications should be treated by investigating whether or not decompression of the optic nerve is effective.

Clinical effects of endonasal sinusectomy with reconstruction of the nasal cavity (Takahashi's method).

A follow-up investigation of the results of endonasal sinusectomy with reconstruction of the nasal cavity (Takahashi's method) was carried out in 535 of 1338 patients who underwent endonasal sinusectomies during the 6-year period from 1967 to 1972. The subjective results were as follows: cured 196 (36.6%); improved 234 (47,5%); unchanged 69 (12.9%); aggravated 12 (2.2%). In other words, 450 (84.1%) of the patients were satisfied with the results of the operations. Good results have similarly been obtained in allergic nasal disorders spreading in Japan of late, and concomitant reconstruction of the nasal cavity and desensitization therapy have resulted in improved response.

Clinical effects of endonasal sinusectomy with reconstruction of the nasal cavity (Takahashi's method).

A follow-up investigation of the results of endonasal sinusectomy with reconstruction of the nasal cavity (Takahashi's method) was carried out in 535 of 1,338 patients who underwent endonasal sinusectomies during the 6-year period from 1967 to 1972. The results of subjective symptoms were as follows: cured 196 (36.6%); improved 234 (47.5%); unchanged 69 (12.9%); aggravated 12 (2.2%). In other words, 450 (84.1%) of the patients were satisfied with the results of the operations. Good results have similarly been obtained in cases of nasal allergy which shows increasing tendency of late, and concomitant reconstruction of the nasal cavity and desensitization therapy have resulted in improved responses.

Analyses of laboratory data and establishment of reference values and intervals for healthy elderly people.

OBJECTIVE: Protein-energy malnutrition is a common disorder in the elderly. Although serum albumin is commonly used as a nutritional marker, data is lacking on serum albumin levels in the elderly. The purpose of this study was to determine whether serum albumin levels decrease with advancing age and to establish reference value and interval of laboratory data for elderly people (75 years and over). PARTICIPANTS: Blood samples from 13821 healthy people, 42064 outpatients, and 15959 inpatients were collected during 2008. Blood from 127 of our nutrition support team (NST) patients was also collected during August 2006 and May 2009, and analyzed. MEASUREMENTS: Serum albumin, hemoglobin, total cholesterol levels and lymphocyte count were determined. We analyzed the change in each parameter in accordance with age, compared the data for elderly people with younger people, and established new reference values. Clinical outcomes were examined depending on the improved reference values. RESULTS: Albumin was lower in older persons than in younger persons. The estimated reference value and interval were 42 (48-36) g/l in older persons and was much lower in NST patients. Hemoglobin was decreased while cholesterol and lymphocyte count were not changed in older persons: all were markedly decreased in NST patients. Terms of hospital stay were significantly longer and mortality rates were significantly higher in older persons, comparing from above to below using a new reference value of albumin (36 g/l). CONCLUSIONS: The serum albumin level decreases with advancing age, but it was maintained to some extent in healthy older people. Serum albumin levels related to the clinical outcome. Hemoglobin and cholesterol levels and lymphocyte count were all lower in NST patients. These measurements may be valuable markers of nutritional status and can help in guiding the need for nutritional support.

CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model.

Helicobacter pylori causes various gastro-duodenal diseases, including gastric cancer. The CagA protein, an H. pylori virulence factor, induces morphological changes in host cells and may be associated with the development of peptic ulcer and gastric carcinoma. The present study has analysed the role of CagA protein in the pathogenesis of H. pylori infection in the Mongolian gerbil model. Mongolian gerbils were challenged with wild-type H. pylori strain TN2, which has a functional cag pathogenicity island or isogenic mutants with disrupted cagA (DeltacagA) or cagE (DeltacagE) genes. They were sacrificed at 7, 13, and 25 weeks after inoculation. Pathological changes of the gastric mucosa were determined and apoptosis was assessed by the TUNEL assay. Immunohistochemistry for PCNA, phospho-IkappaBalpha, and phospho-Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the DeltacagA mutant induced milder gastritis than did the wild type. The extent of apoptosis and lymphoid follicle formation in the epithelium appeared to depend on intact cagA. The DeltacagA mutant induced less phosphorylation of IkappaBalpha and Erk, and less expression of interferon-gamma and interleukin-1beta mRNA in the epithelium than did the wild type. It is concluded that CagA protein may be essential for the induction of severe gastritis in the Mongolian gerbil model.

Therapeutic performance of nasal and paranasal operations in recent years.

In this survey of the postoperative therapeutic performance of 555 cases of nasal surgery, particularly conservative fiberscopic endonasal sinusectomy, it was found that conservative nasal operations accounted for 87.8% of the entire sample population and the therapeutic effects, (in terms of subjective symptoms) were found to be favorable in 91.5% of cases. These results suggest that conservative nasal operations will become the dominant form of nasal surgery in the future.

Evaluation of amorphous ursodeoxycholic acid by thermal methods.

PURPOSE: The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the thermal methods (microcalorimetry and differential scanning calorimetry (DSC) for studying the amorphous state and clarifying the dissolution mechanism of UDCA. METHODS: Amorphous UDCA was prepared by grinding and rapid cooling of the melts. The heat of solution of UDCA was measured by an isothermal heat-conduction twin microcalorimeter at 25.0 degrees C. Some physicochemical properties of amorphous UDCA were also studied. RESULTS: The intensities of X-ray diffraction peaks of crystalline UDCA decreased with an increase in grinding time. The heat levels of solution of crystalline UDCA and UDCA ground for 1 min were endothermic, and became exothermic with an increase in grinding time. A good correlation was obtained between the heat of solution and the heat of crystallization determined from the peak area in DSC. Although no significant difference was observed in X-ray diffraction patterns of amorphous UDCA prepared by the two methods, significant differences were recognized in DSC, IR and 13C-NMR, and the heat of solution indicated different values among the two samples. The stability of amorphous UDCA samples stored under 74.5% relative humidity at 40 degrees C was found to depend upon the preparation methods. CONCLUSIONS: Different states of amorphous UDCA were obtained depending on the preparation method. The application of thermal methods to evaluate the amorphous state was demonstrated. The mechanism of dissolution of UDCA was discussed from the results of the heat of solution examination.