Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

Epigenetic regulation including DNA methylation plays an important role in several differentiation processes. We profiled global DNA methylation in the neural differentiation of P19 embryonic carcinoma cells using a microarray-based method called MIAMI. We found a genome-wide demethylation of genes. This suggests demethylation rather than methylation is important in neural differentiation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Evaluation of antipsychotic and relative drugs using disruption of prepulse inhibition as an animal model for schizophrenia

The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a subsequent startling stimulus. The PPI, a model of sensorimotor gating, is deficient in patients with schizophrenia and some other psychiatric disorders. In rodents, PPI can be disrupted by methamphetamine or phencyclidine, which causes psychotomimetic symptoms, and the dopaminergic agonist-induced PPI is reversed by dopamine D2 receptor antagonists and a dopaminergic partial agonist aripiprazole. However, in general, the glutamate receptor antagonist-induced PPI is reversed by atypical antipsychotics such as clozapine, but not by typical antipsychotics such as haloperidol. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for screening antipsychotics. Recently, various inbred mouse strains and genetically modified mouse lines have been examined and the studies using PPI indicated the involvement of various neurotransmitters such as dopamine, glutamate, serotonin, GABA and neuropeptide in the biological basis of sensorimotor gating. In addtition, mood stabilizers such as valproate and lamotrigine or alpha7 nicotinic receptor agonists have reported to reverse the PPI disruption.     

Perturbation of secretory Ig A in saliva and its daily variation by academic stress

Objectives Several studies have reported that the secretory immunoglobulin A (S-IgA) concentration in saliva is an indicator of psychological stress. The aim of this study was to clarify the relationship between S-IgA and the stress from academic examinations. Methods S-IgA levels in 10 medical student volunteers from the second year course between May 4 and July 13, 2000 were examined using the ELISA method. Results There was a tendency for S-IgA in saliva to be higher on the day before academic examinations and during them, and lower on the days between these examinations. Conclusions It may be possible to use this measurement to monitor psychological stress in students and workers. Second year medical student in the year 2000.     

Specific therapy of digoxin intoxication in dogs by hybrid kidney overexpressing multidrug resistance protein

BACKGROUND: We have recently developed a unique hybrid artificial kidney, where the proximal tubular cell line, over-expressing multidrug resistance protein, MDR-1 (PCTL-MDR), was cultured on hollow fibers. While this module efficiently removed digoxin in vitro, its efficacy in vivo remained to be determined. METHODS: The system was scaled up by connecting 10 similar modules in parallel, with the MDR-1 (PCTL-MDR) overexpressed proximal tubular cell line cultured as in our previous study. The system was connected to dogs intoxicated with digoxin, a representative substrate of MDR-1. Blood was circulated for 90 minutes through the system. Arterial and venous blood concentrations of digoxin and inulin were monitored. Complete blood cell count and granulocyte elastase were measured before and at the end of the study. RESULTS: By using the system with PCTL-MDR, the arterial digoxin concentration was dramatically decreased from 2.89 +/- 0.10 to 0.92 +/- 0.11 ng/mL, but not by the system with PCTL alone. The clearance was 22.4 +/- 2.1 and 1.5 +/- 0.2 mL/min for the PCTL-MDR and PCTL equipment, respectively. Inulin was not transported in either system. White blood cell and platelet counts were slightly reduced by the treatment while hematocrit was unchanged; the granulocyte elastase concentration was slightly increased. CONCLUSION: These data suggest that our new type of hybrid kidney can selectively remove digoxin sufficiently to reduce its systemic blood concentration in dogs with digoxin intoxication. Taking previous studies into consideration, this system may be a more powerful tool for the treatment of intoxication.     

A new method for measuring total coronary blood flow using the lithium dilution method

BACKGROUND: The aim in this study is to evaluate a new method of measuring total coronary blood flow (TCBF) in (1) an in vitro model and in (2) an animal model by the lithium dilution method. METHODS: (1) Ringer's solution was circulated in a closed circuit with the main flow as a systemic circulation, and the side flow as a coronary circulation by a roller pump. Two peaks originating from the main and side flow were recorded by the lithium dilution method. The flow was calculated using the Fick principle based on the ratio of the areas under the curve. The validity of this method was evaluated by Bland Altman analysis. (2) Four beagles were anesthetized and subjected to insertion of two pulmonary artery catheters. The position of the catheters was confirmed as being in the pulmonary artery and in the right atrium. Lithium chloride solution was injected into the pulmonary artery and the change in lithium concentration at the right atrium was recorded. TCBF was estimated by the method used in the in vitro study. RESULTS: (1) The calculated flow correlated well with the actual flow (r2 = 0.86). (2) The estimated TCBF at baseline, with low-dose nitroglycerin, and with high-dose nitroglycerin was 206 +/- 43.0 mL/min, 304 +/- 50.3 mL/min, and 348 +/- 50.1 mL/min, respectively (mean +/- SE). TCBF was significantly increased by nitroglycerin infusion. CONCLUSION: A new method of measuring TCBF using the lithium dilution method was reliable and useful both in vitro and in an animal model. This may be clinically useful method for measuring TCBF.     

De novo basilar top aneurysm in an elderly patient treated with Guglielmi detachable coils

Ruptured de novo aneurysms, compared with the usual subarachnoid hemorrhage, commonly occur in younger patients and are extremely rare in elderly patients. We discuss their etiology and report the case of a ruptured de novo aneurysm in a 77-year-old woman.     

Renal Arteriovenous Fistula with Rapid Blood Flow Successfully Treated by Transcatheter Arterial Embolization: Application of Interlocking Detachable Coil as Coil Anchor

A 70-year-old woman presented to our outpatient clinic with a large idiopathic renal arteriovenous fistula (AVF). Transcatheter arterial embolization (TAE) using interlocking detachable coils (IDC) as an anchor was planned. However, because of markedly rapid blood flow and excessive coil flexibility, detaching an IDC carried a high risk of migration. Therefore, we first coiled multiple loops of a microcatheter and then loaded it with an IDC. In this way, the coil was well fitted to the arterial wall and could be detached by withdrawing the microcatheter during balloon occlusion (pre-framing technique). Complete occlusion of the afferent artery was achieved by additional coiling and absolute ethanol. This technique contributed to a safe embolization of a high-flow AVF, avoiding migration of the IDC.     

Renal artery stenosis in a patient with Leriche syndrome: brachial artery access for stent placement

We encountered a patient with Leriche syndrome and general atherosclerotic disease. His renal function had deteriorated, and diabetic nephropathy was suspected. Severe left renal artery stenosis was also found and considered, if untreated, to be an important factor in aggravation of his renal function. Because the infrarenal abdominal aorta was completely occluded, we treated the patient by insertion of a stent into the left renal artery from the brachial approach. The operation was successful, without residual stenosis or complications. Renal blood flow was remarkably improved after stent placement.     

Drug interaction between St John's Wort and quazepam

AIM: St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined. METHODS: Thirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day(-1)) or placebo for 14 days. The study was performed in a randomized, placebo-controlled, cross-over design with an interval of 4 weeks between the two treatments. Blood samples were obtained during a 48 h period and urine was collected for 24 h after each dose of quazepam. Pharmacodynamic effects were determined using visual analogue scales (VAS) and the digit symbol substitution test (DSST) on days 13 and 14. RESULTS: SJW decreased the plasma quazepam concentration. The Cmax and AUC(0-48) of quazepam after SJW were significantly lower than those after placebo [Cmax; -8.7 ng ml(-1) (95% confidence interval (CI) -17.1 to -0.2), AUC0-48; -55 ng h ml(-1) (95% CI -96 to -15)]. The urinary ratio of 6beta-hydroxycortisol to cortisol, which reflects CYP3A4 activity, also increased after dosing with SJW (ratio; 2.1 (95%CI 0.85-3.4)). Quazepam, but not SJW, produced sedative-like effects in the VAS test (drowsiness; P < 0.01, mental slowness; P < 0.01, calmness; P < 0.05, discontentment; P < 0.01). On the other hand, SJW, but not quazepam impaired psychomotor performance in the DSST test. SJW did not influence the pharmacodynamic profile of quazepam. CONCLUSIONS: These results suggest that SJW decreases plasma quazepam concentrations, probably by enhancing CYP3A4 activity, but does not influence the pharmacodynamic effects of the drug.