An interesting change of E-selectin in cimetidine administration during anticancer drug use

E-selectin is an adhesion molecule developed as an important material for hematogenous metastasis of cancer cells on vascular endothelial cells. It is expected that if we can restrain a manifestation of E-selectin then hematogenous metastasis can be restrained. We divided gastric cancer and the colorectal cancer patients, who performed chemotherapy, into two groups of cimetidine administrated group and a non-administration group, and reviewed whether cimetidine inhibited an expression of E-selectin on vascular endothelial cells by measuring E-selectin in plasma. We experienced one example that showed an interesting change of E-selectin and the quantity of E-selectin in plasma fell during the cimetidine dosage. However, we report that E-selectin has risen after the cimetidine dosage was cancelled in the cimetidine administrated group.     

Efficient drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by dexamethasone incorporated into liposomes in atherogenic mice

In order to confirm the efficacy of dexamethasone (DXM) incorporated into liposomes (DXM-liposomes) on atherosclerosis, drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by DXM-liposomes were investigated in atherogenic mice. DXM-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to three different particle sizes to clarify the influence of particle size on the drug delivery to atherosclerotic lesions and the effect on atherosclerosis. The particle sizes of DXM-liposomes were 519 nm (L500), 202 nm (L200) and 68.6 nm (L70), respectively. In both size, DXM concentration and DXM/lipid molar ratio in DXM-liposomes suspension were 1 mg DXM/ml and 0.134 mol DXM/mol total lipids, respectively. Atherogenic mice used as an experimental model develop an atherosclerotic lesion in the aorta and they were prepared by feeding an atherogenic diet for 14 weeks. The aortic pharmacokinetics of DXM-liposomes was examined by intravenous administration to atherogenic mice. The aortic uptake clearance of DXM in atherogenic mice treated with L200 was 2.6--3.2 fold greater than that in animals treated with L500, L70 or free DXM (f-DXM). Furthermore, the effects of DXM-liposomes on atherosclerosis were examined by intravenous administration to atherogenic mice once a week from 8 to 14 weeks. The antiatherosclerotic effects of DXM-liposomes were evaluated by determination of the aortic cholesterol ester (CE) level. The aortic CE level in atherogenic mice treated with L200 (55 microg DXM/kg) was significantly lower than that in animals treated with PBS. The antiatherosclerotic effect of L200 (55 microg DXM/kg) was significantly more potent than that of f-DXM (550 microg DXM/kg). These findings suggest that efficient delivery of DXM to the atherosclerotic lesions by L200 induces an excellent antiatherosclerotic effect at a lower dose. Therefore, L200 may be useful in the development of drug delivery systems for atherosclerotic therapy.     

Effect of etidronate on aortic calcification and bone metabolism in calcitriol-treated rats with subtotal nephrectomy

The present study was undertaken to determine the effects of etidronate (ED) on calcitriol-induced aortic calcification and bone metabolism in rats with renal failure. Severe aortic calcification was induced by treatment with calcitriol for 3 weeks in rats in which 5/6 of the kidneys were removed (SNx group). Treatment of ED (10 mg/kg) together with calcitriol after subtotal nephrectomy (SNx) significantly inhibited thoracic and abdominal aortic calcification 3 weeks after the operation; however, ED (2 mg/kg) was ineffective. The serum levels of osteocalcin and pyridinoline decreased in ED (10 mg/kg) treated-renal failure rats compared with SNx rats. Total bone mineral density (BMD) in the SNx group was lower than that in the sham group, in which animals were treated with calcitriol after a sham operation. The total BMD value in the ED (10 mg/kg)-treated group was similar to that in the SNx group, whereas the levels of cancellous BMD were low in the ED (10 mg/kg)-treated rats. Our data show that ED at a dosage that suppresses bone metabolism markedly inhibits vascular calcification in rats with renal failure.     

Cranial subdural hematoma after inadvertent dural puncture at epidural anesthesia

Intracranial subdural haematoma has been reported to be an exceptionally rare complication of accidental dural puncture. An accidental lumbar dural puncture occurred in a 36-yr-old male undergoing orthopedic knee surgery. On the morning after the operation, the patient complained of severe occipital headache, although this was relieved with loxoprofen and rest. This was assumed to be a postdural puncture headache (PDPH) because it had a postural component (it was worse on sitting up). On the third day after the operation, the patient developed a severe diffuse headache together with nausea, which did not subside with analgesia and bed rest. Magnetic resonance imaging of the head showed a small acute subdural hematoma in the bilateral temporooccipital region with no mass effect. The patient was conscious and oriented. There was no focal neurological deficit. The patient was managed conservatively with bed rest and intravenous fluids. His condition improved without surgical decompression and was discharged on the 40 th day after the operation. Severe and prolonged PDPH shoud be considered as a warning sign of an intracranial complication.     

Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway rats fed raffinose and alpha-linked galactooligosaccharide

We recently found that dietary raffinose suppressed allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats. Using this model in the present study, we compared the efficacy of other oligosaccharides with that of raffinose. Brown Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt. 1, rats were fed a control diet or diets supplemented with different oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide, fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the fluid was significantly lower in rats fed raffinose and alpha-linked galactooligosaccharide diets than in those fed the control diet. Dietary fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia. In Expt. 2, i.p. administration of raffinose and alpha-linked galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide, suppressed airway eosinophilia in rats fed the control diet. In Expt. 3, suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide occurred in cecectomized rats administered neomycin. Reduced levels of interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the suppression of airway eosinophilia. We propose that indigestible oligosaccharides differ in their suppressive effect on allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats and that the effect appears not to be mediated by intestinal microflora.     

Case-mix payment in Japanese medical care

The Japanese medical care system, highly rated internationally, has recently experienced a crisis that has placed a burden on all of its citizens, providers, and payers, due to the expansion of medical expenditures in rapidly aging society with the stagnant economy. To address this, in April 2003, Japan implemented a case-mix payment system, instead of conventional fee-for-service payment, based on an original case classification with 2552 groups (Diagnosis Procedure Combination: DPC), with inpatients from 82 special functioning hospitals. This system contains two parts: per diem prospective payment for hospital's fee with a three-level step down according to average length of stay for each diagnosis group, which is adjusted to secure the previous year's remuneration in each hospital; fee-for-service payment for doctor's fee based on national fee schedule. The payment system reduced average length of stay, but did not change inpatient expenditures and increased outpatient expenditures. The in-hospital mortality rate, although un-adjusted, did not changed, but the readmission rate increased mainly through an increase in planned, not accidental, readmissions. For the expansion of this system, ongoing program refinement, reflecting the results of data analysis, is indispensable.     

Three cases of pulmonary hamartoma appearing after radical nephrectomy for renal cell carcinoma

We report 3 patients with pulmonary hamartoma, all of whom had undergone nephrectomy for renal cell carcinoma. A lung tumor was detected 2 to 9-months following nephrectomy. Preoperative diagnosis was pulmonary metastasis from renal cell carcinoma and pulmonary tumor resection was performed in each case. There was a 9- to 12-month interval between the detection and resection of the lung tumor. The histological diagnosis of the lung tumor in all three patient was pulmonary hamartoma. Following the resection of the lung tumor, recurrence was not noted in any of the patients.     

Evaluation of the relationship between periapical lesions/sclerotic bone and general bone density as a possible gauge of general health among 80-year-olds

OBJECTIVES: To evaluate the incidence among 80-year-olds of periapical lesions as detected on panoramic radiographs and to determine the relationship between sclerotic bone around the periapical lesions to heel bone density, body height, and hand-grip strength. STUDY DESIGN: Six hundred fifty-nine panoramic radiographs (262 males, 397 females), obtained from 80-year-old residents of Fukuoka Prefecture, Japan, were used for evaluation of periapical lesions. These findings were correlated with physical examination results to determine the relationship to general health. RESULTS: Of 659 panoramic radiographs, 31 (5%) were noted to have periapical lesions. Average size of the 31 periapical lesions was 6.1 +/- 2.2 mm. Of the 31 periapical lesions, 21 (68%) were accompanied by linear or diffuse types of sclerotic bone. Of the 21 sclerotic bones, 10 (48%) were of a linear type of sclerotic bone and 11 (52%) of a diffuse type of sclerotic bone. Of the 11 diffuse types of sclerotic bone, 10 (91%) were in the mandible and 1 (9%) in the maxilla. Periapical lesions in the mandible were more frequently accompanied by a diffuse type of sclerotic bone than those in the maxilla (P < .01). The hand-grip strength of those having periapical lesions, accompanied by a diffuse type of sclerotic bone, was stronger than those having no periapical lesions (P < .01) and those accompanied by a linear type of sclerotic bone (P < .03). However, there was no relationship between presence of sclerotic bone and heel bone density or body height. CONCLUSIONS: Periapical lesions accompanied by a diffuse type of sclerotic bone were more frequently seen in the mandible of 80-year-olds. To evaluate the clinical significance of sclerotic bone around periapical lesions in 80-year-olds, further study to evaluate the significance of endodontic treatment needs to be done.     

Placental transfer and body distribution of nickel chloride in pregnant mice

Placental transfer and body distribution of NiCl₂ were studied in pregnant mice (ICR strain, 12–14 weeks old). A single injection of NiCl₂ (4.6 mg/kg as Ni ip) was administered on the 16th day of gestation. Animals were killed at intervals of 2, 4, 6, 8, 10, 24, 30, and 48 hr after the injection and tissues were obtained for measurement of nickel concentration. Concentration of nickel in blood and placentas were found to be at maximum level (19.8 and 3.9 μg/g) 2 hr after injection, and those in liver, spleens, and kidneys reached maximum levels of 4.9, 1.3, and 56.2 μg/g, respectively, 4 hr after injection. Maximum concentration in fetal tissues (1.1 μg/g) was reached 8 hr after injection, and a slight gradual decrease was observed during 24 hr. Thereafter, there was a rapid decrease. The relative concentrations of Ni in blood, organs, and tissues of pregnant mice at 24 hr after injection were found in order from highest to lowest concentration: Kidneys > blood > placentas > fetuses ? liver > spleen. It is estimated that the Ni will be excreted in about 42 to 84 hr after injection from the calculated biological half-times.