Expression of tight and gap junctional proteins in the perineurial window model of the rat sciatic nerve

Limited perineurial injury, known as a perineurial window, can lead to neuropathic pain. This article hypothesizes that the recovery of the perineurium is associated with the intercellular junctional proteins. It analyzes the expressions of occludin, ZO-1, and connexin 43 by immunoconfocal microscopy. Seven days after injury, immunoreactivities for occludin and ZO-1 were observed, although there was no connexin 43 detected. Then, 21 days after injury, immunoreactivity for connexin 43 were observed. These results indicate that recovery of the perineurium is associated with the intercellular junctional proteins and that the recovery of gap junctions is delayed compared with that of tight junctions.     

Characterization of two novel mutations of the antithrombin gene observed in Japanese thrombophilic patients

We investigated the molecular basis of reduced functional levels of antithrombin (AT) in two individuals suffering from thromboembolic events. In each case direct sequencing of amplified DNA revealed 13,260-13,262 del in one patient and 2511C>A in the other patient, predicting a heterozygous E381del and P16H, respectively. Both patients had no 20210A allele and factor V Leiden mutation. To understand the molecular mechanism responsible for antithrombin deficiency, stable expression experiments were performed using HEK293 cells transfected with the expression vector containing the wild-type or the mutated recombinant cDNA. In these experiments, the media levels of the two mutated antithrombins were the same as that of wild type, but the specific activity of the E381del mutant decreased significantly compared with that of wild type. These results showed that the E381del mutation was responsible for type II deficiency, whereas the other mutation, P16H, did not produce any definite abnormality which could contribute to antithrombin deficiency.     

Bispectral index monitoring in fast track pediatric cardiac surgery

BACKGROUND: We evaluated the changes in the bispectral index (BIS) as a potential indicator of level of consciousness in infants and children undergoing fast track cardiac surgery. METHODS: Twenty-one children undergoing fast track cardiac surgery were recruited into this study. Anesthesia was maintained with inhaled sevoflurane and intravenous fentanyl 10 microg x kg(-1). Cardiopulmonary bypass (CPB) with mild hypothermia and an immediate tracheal extubation protocol were used. BIS was recorded throughout the operation. RESULTS: In average, BIS was kept almost under 70 with 0.5-3.0% of sevoflurane. During rewarming from mild hypothermia, BIS increased temporarily over 70 in about a half of children. We, therefore, treated them by increasing sevoflurane concentration. Nineteen children were extubated in the operating room, and two patients were extubated in ICU within three hours after surgery. CONCLUSIONS: BIS was kept within the level of adequate sedation during surgery. However, since the increase in BIS during the rewarming phase could reflect light anesthesia, caution should be taken around this phase.     

In vitro chemosensitivity test for hepatocellular carcinoma using collagen-gel droplet embedded cultures

This study evaluated an in vitro assay for chemosensitivity test using a collagen-gel droplet-embedded culture drug sensitivity test (CD-DST) for hepatocellular carcinoma (HCC). In 25 patients with HCC, in vitro chemosensitivity to 5-fluorouracil (5-FU), epirubicin (EPI), and cisplatin (CDDP) was examined by CD-DST, and 5-FU, EPI, and paclitaxel (PTX) were examined in 38 patients with breast cancer. Successful rates of chemosensitive evaluation by CD-DST were 64% for HCC and 79% for breast cancers. Although chemosensitivities of breast cancer were 5-FU 23.1%, EPI 83.3%, and PTX 67.7%, only one HCC sample was sensitive to EPI. Growth rates of HCC for 7 days of culture were significantly lower than those of breast cancers (1.04 vs 3.61). The culture methods for HCC in CD-DST should be improved to estimate accurate results.     

Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans

OBJECTIVES AND METHODS: We assessed the relationship between the metabolism of R- and S-mephobarbital (MPB) and genetic polymorphisms of cytochrome P450 (CYP) 2C19 and CYP2B6. Nine homozygous extensive metabolizers (homo-EMs, 2C19*1/2C19*1) of CYP2C19, ten heterozygous EMs (hetero-EMs, 2C19*1/2C19*2, 2C19*1/2C19*3) and eleven poor metabolizers (PMs, 2C19*2/2C19*2, 2C19*3/2C19*3, 2C19*2/2C19*3) recruited from a Japanese population, received an oral 200 mg-dose of racemic MPB. Blood and urine samples were collected, and R-MPB, S-MPB and the metabolites, phenobarbital (PB) and 4'-hydroxy-MPB, were measured. Each subject was also genotyped for CYP2B6 gene. RESULTS: The mean area under the plasma concentration-time curve (AUC) of R-MPB was 92-fold greater in PMs than in homo-EMs. R/S ratios for AUC of MPB were much higher in PMs than in EMs (homo- and hetero-). The cumulative urinary excretion of 4'-hydroxy-MPB up to 24 h postdose was 21-fold less in PMs than in homo-EMs. The metabolic ratio of AUCPB/(AUCS-MPB + AUCR-MPB) was higher in PMs than in EMs (homo- and hetero-). In addition, this metabolic ratio was lower in the carriers of CYP2B6*6 compared with that in its non-carriers. CONCLUSIONS: Our results indicate that the 4'-hydroxylation of R-MPB is mediated via CYP2C19 and that the rapid 4'-hydroxylation of R-MPB results in a marked difference in the pharmacokinetic profiles between R-MPB and S-MPB in the different CYP2C19 genotypic individuals. In addition, a minor fraction of the interindividual variability in PB formation from MPB may be explainable by the CYP2B6*6 allele.     

Short and long-term hypotensive effect of timolol-gel and latanoprost instillation in normal-tension glaucoma

PURPOSE: To confirm the predictive value of the results of a 4-week trial of latanoprost alone, timolol-gel alone, or a combination of the two in normal-tension glaucoma (NTG) patients, when compared with the hypotensive response after a 6-month trial using the same combination of eye drops for the same patients. METHODS: One eye each of 45 NTG patients was used in a prospective 4-week trial of latanoprost alone, timolol-gel alone, or a combination of the two. Patients continued using the eye drops for 6 months, according to the results of the trial. The correlation of the results of the 6-moth use and the baseline data, and the baseline data and the results of the 4-week trial were evaluated by the paired-t test. RESULTS: The intraocular pressure(IOP)s of patients using timolol-gel alone were 13.9 mmHg at the base line, 9.7 mmHg after the trial, and 12.0 mmHg after 6-month use(baseline, trial: p < 0.05). IOPs when using latanoprost alone were 15.3 mmHg at baseline, 11.7 mmHg after the trial, and 11.5 mmHg after 6-month use(baseline: p < 0.05, trial: p = 0.33). IOPs using timolol-gel and latanoprost in combination were 14.8 mmHg at baseline, 11.4 mmHg after the trial, and 12.0 mmHg after 6-month use (baseline: p < 0:05, trial: p = 0.14). CONCLUSION: The result of the 4-weeks trial of latanoprost alone or in combination with timolol-gel can be indicative of the IOP after 6-month use.     

Macular thickness after cataract surgery in diabetic patients

PURPOSE: Macular edema after cataract surgery is the main cause of unfavorable visual outcome and more common in diabetic patients. The objective of this study was to evaluate the time course of change in macular thickness in diabetic patients, compared with that in nondiabetic patients after uneventful cataract surgery. SUBJECTS AND METHODS: We examined 36 diabetic eyes and 30 nondiabetic controls preoperatively and 1, 3, 7, 30, 90, and 180 days postoperatively, using a Retinal Thickness Analyzer (RTA). Aqueous flare intensity and visual acuity were also measured. RESULTS: Macular thickening and an increase in aqueous flare were marked in diabetic eyes and controls on the first postoperative day. In nondiabetic patients, these subtle changes improved gradually and returned to near-normal within 6 months. In diabetic patients, prolonged and progressive macular thickening was observed 6 months after surgery. Macular edema in diabetic patients had a propensity to cause poorer 6-month visual acuity. CONCLUSIONS: RTA is useful for early detection of macular edema. Using RTA, we demonstrated that cataract surgery induced subclinical macular edema even in nondiabetic subjects and that progressive macular edema might cause poor visual outcome in diabetic patients.     

A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.