Intracranial sites regulating the biphasic action of progesterone in estrogen-primed golden hamsters

Diencephalic and mesencephalic neural sites regulating the biphasic effect of progesterone (P) were investigated using the hormone implantation technique in ovariectomized female golden hamsters primed with estrogen. Double barreled cannulae were implanted unilaterally and bilaterally in the medial preoptic area, anterior hypothalamus, ventromedial hypothalamus (VMH), central gray, or interpeduncular nucleus. Testing was conducted using a sequential paradigm; facilitation tests commenced after 44 h of estrogen priming. P-filled cannulae placed in the VMH region facilitated lordosis behavior in 42% and 60% of unilaterally and bilaterally implanted females, respectively. In the anterior hypothalamus, only P implants adjacent to the VMH area effectively promoted receptivity. Lordosis behavior was also observed in 20-36% of females with P implants in the medial preoptic area. P implants in central gray and interpeduncular nucleus regions had no significant facilitating effect on sexual behavior. Tests for inhibition occurred 24 h after facilitation testing and consisted of a pretest, followed by systemic P administration and a behavioral test 4-5 h later. During the pretest for inhibition, females that were receptive in the facilitation test attacked males more rapidly than previously nonreceptive animals and showed decrements in lordosis scores after systemic P delivery. This biphasic effect of P completely inhibited receptivity among several animals in the VMH group. Additional experiments, however, investigating the biphasic effect of P implants in the VMH suggested that the occurrence of copulation in the facilitation test may have been involved in mediating the subsequent increase in aggressive behavior and the suppression of sexual responsiveness in the inhibition test. Nevertheless, a final experiment showed that when P was implanted sequentially in the VMH, facilitation and, more importantly, a later reduction in lordosis behavioral scores occurred even when copulation was eliminated in the facilitation test. P implants in mesencephalic regions exerted no significant inhibitory effect on receptivity. These findings demonstrate that the biphasic action of P in the female hamster is regulated by nerve cells located in the diencephalon, especially in the VMH region.     

Cerebral vasculitis secondary to Wegener's granulomatosis: computed tomography and angiographic findings

The central nervous system is rarely involved by Wegener's granulomatosis. A case of Wegener's granulomatosis with involvement of the cerebral arteries was reported. Computed tomography showed extensive brain edema with angiographic demonstration of cerebral vasculitis.     

Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients.

1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls).     

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.     

A case of acetaminophen-induced pneumonitis]

A 20-year-old woman took 1.2 g of acetaminophen for toothache. She subsequently developed a dry cough, pyrexia, and dyspnea. Chest X-ray revealed diffuse reticulo-nodular shadows in both lung fields. Broncho-alveolar lavage examination showed a marked increase in the total cell number and an increase in the percentage of eosinophils, neutrophils, and lymphocytes. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms resolved, and pulmonary function and chest X-ray findings improved remarkably. The lymphocyte stimulation test was positive for Norshin and its acetaminophen element. Based on these findings, the diagnosis of acetaminophen-induced pneumonitis was made. Acetaminophen intoxication is well-known, but to our knowledge this is the first reported case of acetaminophen-induced allergic pneumonitis in Japan.     

MR angiography of thoracic outlet syndrome.

Thoracic outlet syndrome is a disorder caused by neurovascular compression of the brachial nerve plexus and the subclavian artery or vein by bones and muscles. We report the MR angiographic findings of a patient with thoracic outlet syndrome.     

A new method for monitoring the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA.

We developed a new method for monitoring the cerebrovascular response to acetazolamide using technetium-99m diethylenetriaminepentaacetic acid human serum albumin (99mTc-DTPA-HSA). We infused 740 M Bq (20 mCi) of 99mTc-DTPA-HSA intravenously and carried out dynamic scanning of the anterior view of the head for 50 minutes. Ten minutes after the start of scanning, 1,000 mg of acetazolamide was injected intravenously. In three normal volunteers, the radioactivity in brain increased for an average of 8 minutes after the injection of acetazolamide and then remained relatively stable. The average of dilatation index [(peak count/the count just before acetazolamide injection-1)x 100] was 16.1. Our method enabled us to observe vasodilation caused by acetazolamide straight, and may be of value in assessing cerebral perfusion reserve easily and quantitatively.