Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine.

The present study was undertaken to examine whether the second generation antibiotic drug minocycline attenuates behavioral changes (eg, acute hyperlocomotion and prepulse inhibition (PPI) deficits) in mice after the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801 (dizocilpine). Dizocilpine (0.1 mg/kg)-induced hyperlocomotion was significantly attenuated by pretreatment with minocycline (40 mg/kg). Furthermore, the PPI deficits after a single administration of dizocilpine (0.1 mg/kg) were attenuated by pretreatment with minocycline (10, 20, or 40 mg/kg), in a dose-dependent manner. Moreover, in vivo microdialysis study in the free-moving mice revealed that pretreatment with minocycline (40 mg/kg, i.p.) significantly attenuated the increase of extracellular dopamine (DA) levels in the frontal cortex and striatum after administration of dizocilpine (0.1 mg/kg), suggesting that the inhibition of dizocilpine-induced DA release by minocycline may, at least in part, be implicated in the mechanism of action of minocycline with respect to dizocilpine-induced behavioral changes in mice. These findings suggest that minocycline could attenuate behavioral changes in mice after the administration of the NMDA receptor antagonist dizocilpine. Therefore, it is possible that minocycline would be a potential therapeutic drug for schizophrenia.     

Urological emergency in neonates with congenital hydronephrosis

OBJECTIVE: It is well described that unilateral pelviureteric junction obstruction (PUJO) is a benign condition, because the dilatation resolves spontaneously and the function does not decrease in most of the kidneys. However, there is exceptional PUJO that requires emergent treatment in neonatal periods. The aim of this article is to report the urological emergency and management in neonates with PUJO. MATERIALS AND METHODS: Nine children (seven boys and two girls) with PUJO who underwent neonatal emergent treatment during the last 13 years were reviewed. Renal function was evaluated according to decay curve of serum creatinine (SCr) levels corresponding to gestational age (GA) at delivery. Physical examination, ultrasonographic monitoring, and chest and abdominal plain radiographs were repeated in each neonate. RESULTS: Eight patients were detected prenatally. In five patients, multicystic dysplastic kidney (MCDK) was demonstrated on the contralateral side. Three patients underwent percutaneous puncture of fetal hydronephrosis. Decrease of amniotic fluid was evident in three fetuses. Indications for emergent treatment included mass effect from hydronephrosis in three patients, renal dysfunction in five, and severe urinary tract infection in one. During neonatal periods, a percutaneous nephrostomy tube was placed in seven, and open nephrostomy in one with anorectal malformation. Repeated punctures of the dilated renal pelvis were done in one patient. Renal function after pyeloplasty was stable in eight patients, while it was moderately decreased in one who was associated with oligohydramnios in utero. CONCLUSION: Indications for emergent treatment in neonates with PUJO included mass effect from giant hydronephrosis, renal dysfunction and severe urinary tract infection. At birth, respiratory and circulatory conditions must first be stabilized. In neonates with hydronephrosis of the solitary kidney or severe bilateral PUJO, serial SCr should be monitored to evaluate renal function. Decrease of amniotic fluid suggested renal functional compromise that would not recover after urological management.     

Surgical treatment for ureterocele with special reference to lower urinary tract reconstruction

OBJECTIVES: We reviewed the results of surgical treatment for children with ureterocele, especially addressing the importance of the lower urinary tract reconstruction. METHODS: We present medical records of 91 children with ureterocele (31 with the intravesical type, and 60 with the ectopic type) treated during the last 14 years. As the initial treatment, we carried out transurethral incision of the ureterocele (TUI). In patients with persistent reflux, breakthrough urinary tract infection (UTI), or signs of bladder outlet obstruction due to a collapsed cele wall, we recommended that patients undergo lower urinary tract reconstruction irrespective of the renal function involved in ureterocele. The average follow-up period was 5 years (ranging 1 year and 6 months to 14 years). RESULTS: Transurethral incision of the ureterocele was carried out as the initial treatment on 68 patients (75%). A total of 34 patients (21 intravesical [68%] and 13 ectopic [22%]) were followed medically after TUI alone. Reconstruction of the lower urinary tract was carried out in 59 patients (65%). Nephroureterectomy combined with bladder level reconstruction was carried out in four children with single system and non-functioning kidney. Follow-up voiding cystourethrography showed that only one girl had reflux, which disappeared after the first follow-up examination. Postoperative UTI occurred in 12 patients (20%) with ectopic ureterocele. Voiding dysfunction was suspected in eight patients. CONCLUSION: We believe that the primary objective for patients with ureterocele, especially of the ectopic type, is to reconstruct the original pathology of the lower urinary tract that may give rise to reflux, obstruction, or abnormalities of urination. Although surgery at the bladder level can be challenging, the lower urinary tract reconstruction successfully corrects the vesicoureteral reflux and bladder outlet pathology under a cosmetically acceptable incision.     

Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

PURPOSE: To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. METHODS: This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. RESULTS: In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. CONCLUSIONS: The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.     

Assembly, disassembly, and exchange of glial fibrillary acidic protein

The kinetics and dynamics of glial fibrillary acidic protein (GFAP) assembly was explored by a fluorescence energy transfer assay method. Purified GFAP was stoichiometrically labeled at a single cysteine residue with fluorescein-maleimide. Soluble labeled GFAP in a low ionic strength buffer was assembled into 10 nm filaments by rapidly increasing the ionic strength, and the kinetics of GFAP assembly was monitored by the reduction in fluorescence due to self-quenching of fluorescein. The extent of fluorescence quench correlated with both the formation of 10 nm filament morphology and the amount of protein pelleted at 12,000g. The assembly of GFAP is critically dependent upon both protein and magnesium ion concentration, and at the critical concentration for GFAP assembly is approximately 40 micrograms/ml. Disassembly of GFAP filaments was also observed as a relief of fluorescence quenching after dilution of labeled GFAP filaments. When labeled GFAP filaments were mixed with an excess of unlabeled filaments, a rapid increase of fluorescence was observed, which is due to an exchange of subunits between labeled and unlabeled GFAP filaments. These results indicate that GFAP filaments are dynamic structures and that a small pool of kinetically active unassembled GFAP subunits are in a dynamic equilibrium with assembled GFAP filaments. The ability of GFAP to assemble, disassemble, and undergo subunit exchange has important implications for the organization and dynamics of astroglia cell cytoskeleton during development and in response to injury.     

Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center.

This report concerns the long-term outcome of living donor liver transplantation (LDLT) for pediatric patients at a single center. Between June 1990 and December 2003, a total of 600 LDLTs, including 568 primary transplantations and 32 retransplantations, were performed for pediatric patients, who were immunosuppressed with FK506 and low-dose corticosteroids. Patient survival at 1, 5, and 10 years were 84.6%, 82.4%, and 77.2%, respectively, and the corresponding findings for graft survivals were 84.1%, 80.9%, and 74.5%. Multivariate analysis demonstrated that fulminant hepatic failure (FHF), a graft vs. body weight (GBWR) ratio of <0.8, and ABO-incompatible transplants were independently associated with both patient and graft survival. The retransplantation rate was 6%, and 55 patients (9.7%) have been completely weaned off immunosuppressants. Long-term patient and graft survival after pediatric LDLT for a large cohort of children at our hospital were found to be as good as those for cadaveric liver transplantation, although this series includes 13% liver transplantations with ABO-incompatible donors, which are obviously inferior in patient and graft survival. To obtain better outcomes for patients with FHF and for patients with ABO-incompatible transplants, immunosuppressive therapy needs to be improved.     

Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–2 and Anti–CD3 Monoclonal Antibody Combination Therapy

We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–N^G–monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO₂^–+ NO₁ was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times10¹ U, twice, If) induced a further increase. The NO₂, + NO_3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.     

Prophylactic effect of UFT on the recurrence of bladder cancer

To evaluate the effect of UFT, a mixture of ftorafur and uracil in a ratio of 1:4, in preventing postoperative recurrence of bladder cancer, we performed a randomized controlled study with a non-medication group as control. UFT was given orally 400 mg a day for 6 months. Of 111 patients, 56 were given UFT and 55 were followed up without any medication. The non-recurrence rate in the group treated with UFT was 62.8% after 1 year and 36.3% after 2 years of follow up, and that of the control group was 45.7% and 39.5%, respectively. The rate of non-recurrence in the UFT group was significantly higher (p less than 0.05) than that of the control group during the period of follow up for 2 years. The incidence of side effects was 6.8% in UFT patients. These results indicate the clinical usefulness of prophylactic administration of UFT for bladder cancer patients.     

Skullbase-penetrating injuries caused by umbrella tips: case reports

Two cases of skullbase-penetrating injuries caused by umbrella tips are reported. Case 1: 24-year-old male. Admitted with disturbance of consciousness, left hemiparesis, nasal bleeding, and laceration of left lower eyelid because of having been stabbed by an umbrella tip. Pupils and fundi revealed no definite findings. Plain skull X-ray showed turbid ethmoid sinus and fracture of planum sphenoidale. Cranial CT showed right putaminal hematoma with intraventricular hemorrhage and pneumocephalus. Increased ICP necessitated surgery two days after the injury. Dural laceration of planum sphnoidale, laceration of left optic nerve, right rectal gyrus contusion and rebleeding from the right lenticulostriate branch were observed. Dural plasty and removal of hematoma with external decompression were carried out. He had a good postoperative course, but left visual loss and left hemiparesis remained. Case 2: 29-year-old male. Admitted with excoriation of his right nostril because of having been stabbed by an umbrella tip, severe headache, and nasal discharge. Oculomotor palsy was observed as well as CSF rhinorrhea and meningeal irritability. Plain skull X-ray showed niveau in sphenoidal sinus, pneumocephalus, and fracture of sella turcica. His complaint disappeared after conservative therapy. We reviewed the literature and found only 4 similar cases. The skullbase, because of its anatomical character, is likely to be penetrated in orbital and periorbital injury caused by umbrella tips. Cases which include disturbance of consciousness have a poor prognosis. We hope the fact that umbrella tips can easily become life-threatening objects will come to the attention of the general public so that similar cases may be avoided.     

Curing effects of chlorination, ozone and UV treatments on plasmid DNAs

Curing effects of chlorine, ozone and ultraviolet (UV) on plasmid DNAs were investigated as one of the measures of bio-hazards due to recombinant plasmids. For donor strains of plasmids, Pseudomonas aeruginosa RM 2046 harboring the self-transmissible plasmid R68 and RM 2021 harboring the cloning vector R1162, Escherichia coli C 600 ML 4903 and ML 1410 harboring the self-transmissible plasmid Rts-1 and RP4, and E. coli JM 109 harboring the cloning vector pBR 322 were used. The curing rate showed a tendency to increase with treatment time in a L-shaped curve for each plasmid DNA. The rates reached steady state after more than 5-10 minutes of the chlorination and ozone treatment, or 5-10 seconds of the UV treatment, independent of the treatment intensity. It became clear by use of replica technique that effective curing took place by chlorination for Rts-1, R1162 and pBR322, by ozone treatment for R68, and by UV treatment for PR4, respectively. Of the three disinfection treatments excellent curing effect occurred with chlorination, as more than 90% of the curing rate was obtained by that treatment for all donor strains.