KA Group Research Articles

Role of cerebrospinal fluid-contacting nuclei in maintenance of chronic itch in rats

Objective To evaluate the role of cerebrospinal fluid-contacting nuclei (CSF-CN) in maintenance of chronic itch in rats.Methods Forty-two adult male Sprague-Dawley rats,aged 3 months,weighing 240-280 g,were used in the study.The experiment was performed in two parts.Part Ⅰ Forty-two Sprague-Dawley rats were randomly divided into 3 groups (n =14 each):control group (C group),acetone group (A group) and oxazolone group (O group).0.5％ oxazolone 15 μl was applied to the neck and back of rats in group O,while the equal volume of normal saline and acetone was applied in groups C and A,respectively.Application of the drug mentioned above was repeated on day 7,9,13,16,17,18,21 and 23 after the first stimulation in each rat in each group.Scratching behaviors were oberserved within 30 min after each stimulaiton.Six rats in each group were chosen and sacrificed after the last application of oxazolone,and the brains were obtained for determination of c-Fos expression in CSF-CN.Part Ⅱ Twenty-four rats were randomly divided into 3 groups (n =8 each):control group (C1 group),chronic itch group (group CI),and chronic itch + lesion group (CI + KA group).Chronic itch was induced by repeated application of oxazolone as previously described in CI and CI + KA groups.The chemical lesion of CSF-CN was performed at 6 h after 8th application of the drug.Then the scratching behaviors were observed within 30 min after 9th application of the drug.Results Part Ⅰ Compared with C group,the scratching behaviors were increased significantly at T4-8 in A group,and at T1-8 in O group (P ＜ 0.05),and the expression of c-Fos was up-regulated in O and A groups (P ＜ 0.05).Compared with A group,the scratching behaviors were increased significantly at T1-8 and the expression of c-Fos was up-regulated in O group (P ＜ 0.05).Part Ⅱ Compared with C1 group,the scratching behaviors were significantly increased in CI and CI + KA groups (P ＜ 0.05).The scratching behaviors were significantly reduced in CI + KA group compared with CI group (P ＜ 0.05).Conclusion CSF-CN is involved in the maintenance of chronic itch in rats. Key words: Neurons; Pruritus; Cerebrospinal fluid-contacting nucleus

The kidney expression of matrix metalloproteinase-9 in the diabetic nephropathy of Kkay mice

Background Disorder of the extracellular matrix has been suggested to play a role in the development of diabetic nephropathy. The aim of the present study was to examine the expression of matrix metalloproteinase-9 (MMP-9) in the kidney of Kkay mice, a type 2 diabetic model. Methods Eight Kkay control mice (KA) and eight Kkay diabetic mice (KB) were fed with the same diets for 4 months and sacrificed after glucose levels and weight were measured. The renal pathological changes were examined by periodic acid–Schiff and periodic acid–silver methenamine staining, and the glomerulosclerosis indexes (GIs) were calculated. The levels of MMP-9 protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-9 was measured by reverse transcription polymerase chain reaction. Results The diabetic group had morphological findings of diabetic nephropathy, and their GI (240.0±17.3) was much higher than that of the control group (118.4±15.1) ( P<.01). The mean positive area of MMP-9 protein in the glomeruli of Kkay mice in the KB group was higher than that in the KA group. The expression of MMP-9 messenger RNA level in the diabetic KB group was up-regulated when compared with the KA group. Conclusion The expression of MMP-9 in the kidney of mice with diabetic nephropathy was enhanced, and MMP-9 might be involved in the development of diabetic nephropathy.

The efficacy of optimal doses of intramuscular ketamine and midazolam injections for procedural sedation in laceration repair of children

Purpose:We reported previously that intramuscular ketamine with adjunctive midazolam is more effective than ketamine alone in pediatric procedural sedation, but with limited satisfactory sedation by suboptimal ketamine dose. The optimal dose of intramuscular ketamine in children has never been studied in Korea. In this study, we investigated the effectiveness and adverse events of ketamine 4mg/kg with adjunctive midazolam in pediatric laceration repair. Methods:From Jan. 2005 to July 2005, we enrolled 60 children, aged 3 months-7 years, who needed laceration repair under sedation. After verbal consent from parents, patients were randomly assigned to KMA group(IM ketamine 4 mg/kg＋atropine 0.01 mg/kg＋intramuscular midazolam 0.05 mg/kg) or KA group(without midazolam). We compared both groups with the induction time, recovery time, total sedation time, efficacy of sedation, adverse effects, and the satisfaction score of treating physicians. Results:Potentially confounding variables, age, weight, injury site and anxiety score, were similar between groups. The induction time, recovery time and total sedation time were not different statistically. In KMA group, 90.9 percent of patients showed satisfactory sedation compared to 66.7 percent of KA group(P=0.02) and the occurrence rate of significant adverse effect was 0.0 percent and 37.0 percent respectively. Conclusion:We found adjunctive midazolam with ketamine doses of 4 mg/kg IM produced more effective, satisfactory sedation and less adverse effect than without midazolam in pediatric laceration repair. The emergence phenomenon(agitation during recovery) only occurred in 9 KA group patients. In spite of adverse effect, all patients recovered, were discharged and there were no reported delayed events

Cardiovascular Benefits of Simultaneous Pancreas–Kidney Transplant Versus Kidney Alone Transplant in Diabetic Patients

The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas–kidney transplantation when compared to kidney-alone transplants in diabetic recipients. Patients and methods A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 ± 20 months (range 0–126 months). The duration of diabetes was 24 ± 7 years (range 5–51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). Results Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group ( P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. Conclusions This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas–kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

In order to evaluate the threshold dose of thyroid tumor-promoting effects of KA, male F344 rats were initiated with N-bis(2-hydroxypropyl) nitrosamine (DHPN; 2000 mg/kg body wt., single s.c. injection) and, starting 1 week later, received pulverized basal diet containing 0%, 0.002%, 0.008%, 0.03%, 0.125%, 0.5% or 2%KA for 20 weeks. Five rats each in the 0%, 0.125%, 0.5% and 2%KA groups were sacrificed at week 12, and 10 rats each in all groups at week 20. As an additional experiment, three groups without DHPN initiation received basal diet, a diet containing 0.5% or 2%KA for 20 weeks. The serum T4 levels were significantly decreased in the DHPN-initiated groups given 0.125%KA or more at week 12. No significant decreases in serum T3 levels were observed in the groups treated with DHPN + KA and a significant increase was evident in the 2%KA-alone group at week 20. Some rats in the DHPN + 2%KA group at weeks 12 and 20 and the 2%KA-alone group at week 20 showed pronounced elevation of serum TSH. Thyroid weights were significantly increased in the DHPN-initiated groups receiving 0.5% and 2%KA at weeks 12 and 20 and in the 2%KA-alone group at week 20. Histopathologically, the incidences of focal thyroid follicular cell hyperplasias in the DHPN-initiated groups treated with 0.125%, 0.5% and 2%KA at week 20 were 5/10, 10/10 and 8/8 rats, respectively. At week 20, adenomas were observed in 7/10 rats in the DHPN + 0.5%KA group and 8/8 rats in the DHPN + 2%KA group, and carcinomas were observed in 6/8 rats in the DHPN + 2%KA group. In the groups without DHPN initiation, only focal follicular cell hyperplasia was observed in 1/9 rats in the 2%KA-alone group. These results suggest that the no-observed-adverse effect for the thyroid tumor-promoting effect of KA is 0.03% (15.5 mg/kg/day) under the present experimental conditions, and that KA possesses weak tumorigenic activity in rats due to continuous serum TSH stimulation by a non-genotoxic mechanism.