Long-term treatment with antidepressants increases glucocorticoid receptor binding and gene expression in cultured rat hippocampal neurones.

Since the glucocorticoid receptor (GR) and/or mineralocorticoid receptor (MR) in the hippocampus have been implicated in cortisol feedback of the hypothalamus-pituitary-adrenal (HPA) axis, abnormalities in those receptors might underlie the hyperactivity of the HPA axis described in patients with major depression. Animal studies have shown that long-term in-vivo treatment with antidepressants up-regulates hippocampal GR and/or MR, but it is not clear whether this up-regulation is evoked through a direct action of antidepressants on these receptors. We therefore examined the direct effects of long-term antidepressant treatment on GR binding and the levels of GR messenger RNA (mRNA) in primary cultures of rat hippocampal neurones. The time course of the effects of the tricyclic antidepressants desipramine and amitriptyline on GR binding, as assessed by [3H]dexamethasone binding using RU 28362, a specific agonist for GR, showed a biphasic mode of stimulation: desipramine significantly increased the GR binding with 2-day exposure by 36% over that in controls and by 99% and 60% with 10- and 14-day exposures, respectively. Amitriptyline also led to a significant increase in GR binding, with peaks at 2 (by 60%) and 14 days of exposure (by 60%). The effects of 14-day treatment with desipramine required at least the first 4-day exposure, and the first 10-day exposure was required for the full effect. Northern blot analysis demonstrated that the GR mRNA level was significantly increased by 14-day treatment with desipramine (+142% over control), amitriptyline (+108%), mianserin (+124%), paroxetine (+42%) and sulpiride (+92%), but not with haloperidol. Immunocytochemistry for GR revealed that 2- or 14-day treatment with desipramine significantly increased the number of GR-positive cells with dominant immunoreactivity in the nuclei of granule cell-like neurones or in perikarya of pyramidal cell- and granule cell-like neurones. These findings suggest that tricyclic antidepressants directly increase hippocampal GR by short-term (2-day) and long-term (14-day) exposure, and that the increase by long-term exposure is evoked commonly with different classes of antidepressants through transcriptional up-regulation of GR expression.

Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

Asymptomatic cerebral infarction in Kawasaki disease.

Meningitis, facial palsy, subdural effusion, and cerebral infarction have been reported to be some of the nervous system complications of Kawasaki disease which usually are clinically obvious. A 22-month-old boy with Kawasaki disease, who developed asymptomatic cerebral infarction, is reported. Hyperpyrexia persisted for 57 days; echocardiography and magnetic resonance imaging revealed the presence of aneurysms in the coronary, axillary, and internal iliac arteries. This study indicates that patients with Kawasaki disease may have silent cerebral infarction.

[Occurrence of choroidal neovascularization following photocoagulation treatment for central serous retinopathy].

Occurrence of choroidal neovascularization following laser photocoagulation treatment for central serous retinopathy (CSR) has been reported. We reviewed all the cases of photocoagulation treatment for CSR in our clinic during the past 25 years (1968-1993). Among 1,824 CSR-affected eyes which were treated, choroidal neovascularization occurred in 19 at the site of photocoagulation. In a careful reevaluation of pretreatment fluorescein angiograms, small choroidal neovascularizations were detected in 5 eyes, in which cases the diagnosis of CSR was incorrect. In 3 eyes, choroidal neovascularization was suspected and might have been masked. In the remaining 11 eyes, choroidal neovascularization was not seen. Our survey indicates that, in central serous retinopathy, when the age of the patient is over 50 years, and leakage is weak and parafoveal, choroidal neovascularization may be masked. Laser photocoagulation for these eyes should be conservative with careful, long-term observation.

[Electrophysiologic effects of intravenous digoxin in infants and children with Wolff-Parkinson-White syndrome].

Electrophysiologic properties of the accessory pathway were investigated before and after the intravenous administration of digoxin (0.01-0.02 mg/kg) during electrophysiologic studies in 14 infants and children with the Wolff-Parkinson-White syndrome. Determination of electrophysiologic properties of the accessory pathway was made using transesophageal atrial pacing and/or intracardiac right atrial pacing. Maximal effect on the accessory pathway after intravenous digoxin was observed during one to six hours. Effective refractory period of the accessory pathway increased in 6 of the 14 patients, decreased in 4 and unchanged in 4. Shortest AP 1:1 conduction increased in 5 of the 12 patients, decreased in 3 and unchanged in 4. Tachycardia was not induced after digoxin in only one patient. Tachycardia cycle length, ventriculoatrial conduction time and atrioventricular conduction time were unchanged after digoxin in almost all cases. Thus, digoxin is not the first choice drug for termination and prevention of the preexcitation syndrome.

[Electrophysiologic effects of isoproterenol in children with Wolff-Parkinson-White syndrome].

12 children with the Wolff-Parkinson-White (WPW) syndrome underwent electrophysiologic study before and after the intravenous administration of isoproterenol. Effective refractory period of the accessory pathway and shortest paced cycle length with 1:1 atrioventricular (A-V) conduction via the accessory pathway were shortened after intravenous isoproterenol in all patients. Orthodromic reciprocating tachycardia was induced after isoproterenol in one patient who did not documented tachycardia attack or palpitation before. Anterograde A-V conduction via A-V node and retrograde V-A conduction via accessory pathway were enhanced. Thus, tachycardia cycle length was shortened. Potential high risk group patient who develop hazardous atrial fibrillation during exercise in the WPW syndrome may be selected by isoproterenol infusion.

[Electrophysiologic effects of calcium channel blockers on supraventricular tachycardia in children].

Calcium channel blockers (diltiazem or verapamil) were administered in 17 pediatric patients with supraventricular tachycardia to evaluate their drug effects on electrophysiologic properties and the tachycardia zone. Using electrophysiologic technique, 10 patients were diagnosed as having orthodromic reciprocating tachycardia (ORT), including three patients with concealed atrioventricular bypass tracts. Four patients were diagnosed as having atrioventricular nodal re-entrant tachycardia (AVNRT) of the slow-fast type and three patients were diagnosed as having intra-atrial re-entrant tachycardia (IART). Diltiazem was given to 10 patients; verapamil, to eight patients at doses of 0.15-0.2 mg/kg intravenously. Electrophysiologic properties and the tachycardia zone were then evaluated before and after the administration of calcium channel blockers. Diltiazem and verapamil produced no significant changes in the sinus node and atrial functions including basic sinus cycle length, sinoatrial conduction time, maximum sinus node recovery time and the effective atrial refractory period. Although sinus cycle length was shortened after verapamil in half the cases, it was due to increased sympathetic tone secondary to hypotension rather than to direct action of verapamil. Calcium channel blockers, however, prolonged the PR interval and significantly increased the effective refractory period of the atrioventricular node. Properties of the atrioventricular bypass tracts were not affected by calcium channel blockers. Diltiazem and verapamil were markedly effective in ORT and AVNRT. Their re-entrant circuits, including the atrioventricular node and the tachycardia zones, were shortened or resolved. However, IART showed no significant change in the tachycardia zone after the administration of calcium channel blockers, because the re-entrant circuit was not present within the atrioventricular node.(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-invasive diagnosis of isolated chylopericardium using precordial pericardial imaging after oral administration of 131I-triolein: report of a case].

Chylopericardium is a rare disease and affects both sexes equally from neonate to adult. Usually, there are abnormal connections between the pericardial cavity and thoracic lymphatic systems. These connections are detected by (1) recovery of orally administered Sudan III from pericardial fluid, (2) evidence of radioactivity in the pericardial fluid by paracentesis after oral administration of 131I-labeled triolein, and (3) lymphangiography. However, these method are technically difficult and invasive, thus sometimes dangerous for children. We employed precordial pericardial imaging after oral administration of 131I-labeled triolein on a 9-year-old Japanese girl with isolated chylopericardium before and after surgery. Abnormal connections and the back-ward flow to the pulmonary lymphatics were demonstrated by this method. This is an easy, non-invasive, reliable and safe method for detecting the abnormal connections of pericardial and lymphatic systems in children with chylopericardium.

Myocardial infarction and left coronary ostial stenosis in infancy simulating anomalous origin of the left coronary artery. A case report.

A case of a 3-month-old male infant with myocardial infarction due to left coronary ostial stenosis is presented. Clinically it was quite similar to anomalous origin of the left coronary artery. Postmortem examination revealed quite narrow left coronary ostium and myocardial infarction with aneurysm of the left ventricular apex.

Myocardial involvement in the Marfan syndrome.

A patient with the Marfan syndrome and echocardiographic and angiocardiographic evidence of hypertrophic cardiomyopathy is presented. Endomyocardial biopsy was performed. Histologic abnormalities of the endomyocardium noted in this patient were considered to be related to the basic generalized connective tissue abnormality, and the patient subsequently developed myocardial disease compatible with hypertrophic non-obstructive cardiomyopathy. We believe that this case emphasizes the possible co-existence of subclinical myocardial disease in patients with the Marfan syndrome.

Oral administration of prostaglandin E2 in the hypoplastic left heart syndrome.

Oral administration of prostaglandin E2 resulted in marked clinical and hemodynamic improvement in patients with hypoplastic left heart syndrome. A lessening of metabolic acidosis and an increase in blood pressure were evident. These results indicate that the ductus arteriosus was effectively dilated by oral prostaglandin E2 in patients with ductus-dependent systemic circulation, as in the case of ductus-dependent pulmonary circulation. Surgical risk will also be reduced by pretreatment with oral prostaglandin E2.

Surgical treatment of the Wolff-Parkinson-White syndrome in children.

From 1986 to 1989, seven children ranging in age from 5 months to 16 years underwent surgical treatment for the Wolff-Parkinson-White syndrome at the Shiga University of Medical Science. None of the patients had any other associated congenital heart disease. There was a right free wall accessory pathway in four patients and a left free wall accessory pathway in three. Surgical ablation of these accessory pathways was performed on eight occasions, using the endocardial approach three times and the epicardial approach five. All the children are alive and none has since had episodes of tachycardia. Only one patient had a recurrent delta wave, which was noted 18 months after the operation. Surgical ablation of the accessory pathway for the Wolff-Parkinson-White syndrome can be performed safely, even in infants and children; it is concluded that this useful procedure is capable of improving a patient's quality of life.

Natriuretic peptide receptors, NPR-A and NPR-B, in cultured rabbit retinal pigment epithelium cells.

We tried to detect natriuretic peptide (NP) receptor (NPR-A and NPR-B) mRNAs in cultured rabbit retinal pigment epithelium (RPE) cells and examined the regulation of their expression in relation to subretinal fluid absorption or RPE cell proliferation. RPE cells from 2-4 passages were grown to confluence on microporous membranes and analyzed for levels of expression of receptor mRNAs by quantitative RT-PCR and Northern blotting. The expression of NPR-B mRNA was approximately tenfold higher than that of NPR-A mRNA. The expression of NPR-A mRNA was not affected by treatments that may change subretinal fluid transport, while that of NPR-B mRNA was inhibited by transmitters involved in light- and dark-adaptation such as dopamine and melatonin. Expression of NPR-B mRNA was also suppressed by platelet-derived growth factor and transforming growth factor-beta. Furthermore, atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), ligands for NPR-A and B, respectively, inhibited the proliferation of RPE cells, as analyzed by incorporation of [3H]thymidine. These findings suggest that ANP may be involved in constitutive absorption of subretinal fluid and that NPs form an important regulatory system of proliferation in RPE cells.