Abstract:
The aim of the study was to examine the influence of intrastriatal dopaminergic grafts on the functioning of striatal cholinergic neurons using an in vitro superfusion method. Rats bearing unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system received a cell suspension obtained from ED 14 rat embryonic mesencephali which was injected into the denervated striatum. Lesioned animals displayed an ipsilateral rotation in response to amphetamine (5 mg/kg i.p.). This rotational response disappeared following grafting and there was even a significant contralateral rotation in response to the drug. Apomorphine (0.1 mg/kg s.c.) induced a contralateral rotation following the lesion. This latter response was attenuated in the grafted group. Three months after grafting 350 microns thick slices were prepared from striata from the control and experimental sides of lesioned and graft-bearing animals. The slices were preincubated either with 3H-dopamine (10(-7) M) or 3H-choline (10(-7) M) and then superfused with an oxygenated Krebs-Ringer solution. Stimulation with electrical pulses following preincubation with 3H-dopamine elicited a marked increase of tritium outflow from control slices. Stimulation-evoked overflow was of similar magnitude from slices from striata containing the graft, while it was much reduced in slices from lesioned striata. Amphetamine markedly potentiated the effect of electrical stimulation in slices obtained from control and graft-containing striata. Nomifensine (a dopamine uptake blocker) led to a significant decrease of the overflow of 3H-acetylcholine evoked by electrical stimulation from control striatal slices. This inhibition was antagonized by domperidone, a D2 dopamine receptor blocker, a finding which indicates that the action of nomifensine was indeed due to a potentiation of the action of endogenous dopamine released by the electrical stimulation. A similar, although somewhat attenuated, action of nomifensine and domperidone was observed for striatal slices containing the graft. Amphetamine inhibited the stimulation evoked overflow of 3H-acetylcholine in a dose-dependent manner from striatal slices obtained both from the intact and experimental sides of graft-bearing animals, while it had no action on slices from denervated striata. Finally, the dose-response curve for the inhibition of 3H-acetylcholine release by apomorphine was significantly shifted to the left for slices from the lesioned striata as compared with control slices. This leftward shift was totally abolished in the slices from the graft-containing striatum.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract:
A 54 year-old woman presented with an asymmetrical polyneuropathy, with in addition signs of hepatitis and hypercalcemia. The diagnosis of sarcoidosis was made by hepatic and neuromuscular biopsies. Electrophysiological studies showed an asymmetrical clear neurogenic involvement with an axonal pattern. Ultrastructural study of the nerve showed sarcoid granulomas in epineurium, perineurium and endoneurium, with images of Wallerian degeneration. No features of primary demyelination were found. Granulomas were also present in muscle and liver. Possible etiological mechanisms are discussed: compression of nerve or vessels, or immune angiitis.

Abstract:
The 2 stereoisomers of alphamethyldopa (alpha MD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300-min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose-dependent entry of alpha MD was observed in AH. A stereospecific active transport of alpha MD was evidenced in the AH since the concentration of the L-isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the L-stereoisomer was still observed in CSF. These alpha MD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.

Abstract:
The ability of the 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to affect plasma glucose levels and insulin release was assessed in rats bearing chronic jugular catheters. The i.v. administration of 8-OH-DPAT (150 micrograms/kg) rapidly promoted a transient hyperglycemia. Despite high glucose levels, insulinemia remained constant. Dose-response curves revealed that maximal hyperglycemia was associated with hypoinsulinemia. Increased glycemia, which was also found to be induced by other 5-HT direct and indirect agonists, lasted longer in food-deprived rats. Evidence for a strong inhibitory effect of 8-OH-DPAT on insulin release was reported in rats submitted to i.v. glucose tolerance tests. Pretreatments with the dopaminergic blocker haloperidol, the alpha-1 adrenoceptor antagonist prazosin or the 5-HT2 blocker ketanserin were ineffective. In contrast, the alpha-2 adrenoceptor antagonist idazoxan and the unspecific 5-HT antagonist methiotepin prevented the hyperglycemic and the hypoinsulinemic effects of 8-OH-DPAT. Blockade of these changes by (-)-propranolol (a 5-HT1 blocker), but not by (+)-propranolol, indicated that 5-HT1 and alpha-2 adrenergic receptors mediated 8-OH-DPAT-induced hyperglycemia. Reserpine pretreatment did not prevent the effects of 8-OH-DPAT. Central injection of 8-OH-DPAT induced hyperglycemia, the amplitude of which was equivalent to that measured after i.v. administration. Selective degeneration of serotonergic nerve cells by 5,7-dihydroxytryptamine did not prevent 8-OH-DPAT-induced alterations, thus rendering a key role for presynaptic mechanisms unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract:
Bradykinin (BK), a nonapeptide, originally discovered in blood, is also present in neurons and fibers of the hypothalamus. We tested the putative releasing factor properties of BK on prolactin (PRL) release from anterior pituitary cells in vitro. BK stimulated the release of PRL in a dose-dependent manner, the threshold concentration being in the range. 0.1-1.0 nM. The release of PRL induced by BK at 1 nM concentration was about 2-fold, delayed and sustained over many minutes. Higher concentrations of BK stimulated PRL release in two phases. The shape of the BK-induced PRL release was superficially similar to that induced by thyrotropin-releasing hormone (TRH). 10 nM BK and 10 nM TRH induced about a 4-fold increase in PRL release within 5 min, followed by a gradual recovery to basal secretion. These results indicate that this peptide can act directly at the anterior pituitary gland to release PRL. Phorbol ester also promoted PRL release over the range of 1-10 nM, but the time course of the release was somewhat different.

Abstract:
This study was performed to investigate the effects of exercise on the synthesis of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain of the trained rat. The consequences on the relationships between these two systems were also examined. The sum of the levels of free 3,4-dihydroxyphenyl acetic acid (DOPAC) plus homovanillic acid (HVA) was increased by running and remained elevated throughout the first hour of recovery. Regional studies indicated that the levels of DA were increased in the midbrain, hypothalamus and hippocampus. In these areas, DOPAC showed little variation whereas HVA was largely increased. Administration of pargyline confirmed this increase in the metabolism of DA in hypothalamus and midbrain during running. Food deprivation and administration of tryptophan clearly revealed that running, despite increasing levels of tryptophan and 5-hydroxyindoleacetic acid in brain, reduced the central control of synthesis of 5-HT by tryptophan, probably by inhibiting tryptophan hydroxylase. To examine if such an alteration was caused by the running-induced activation of metabolism of DA in brain, compounds known to affect the activity of DA were used. Administration of amphetamine potentiated the relative inhibition of synthesis of 5-HT induced by running, while alpha-methyl-p-tyrosine prevented this effect of exercise. Haloperidol did not produce any significant change. It is concluded that the control of the synthesis of 5-HT in brain by the availability of tryptophan is altered during exercise and that the increased central catecholaminergic activity participates in such an alteration.

Abstract:
The distributions of perikarya exhibiting human somatocrinin (hGHRF) and neuropeptide Y (NPY) like immunoreactivities (IR) were compared in the arcuate nucleus of colchicine-treated rats. The majority of hGHRF perikarya was found to exhibit simultaneously NPY IR, while virtually no NPY IR was detected in the external layer of the median eminence. It is suggested that the majority of the hGHRF neurons of the rat arcuate nucleus constitutes a tubero-extra-infundibularly projecting system.

Abstract:
In hepatocellular carcinoma, there is modification of cell-to-cell and cell-to-extracellular matrix interactions. Two cases of well-differentiated hepatocellular carcinoma that developed in noncirrhotic livers were explored by light and electron microscopy on perfusion-fixed liver biopsy specimens. In addition, immunocytolocalization of collagen types I, III, and IV, laminin, and fibronectin was assessed. The main features included the following: absence of collagen staining inside the tumor with Sirius red; decrease of collagen types I and III and the increase of collagen type IV, laminin, and fibronectin; widening of Disse's spaces containing numerous, discontinuous, and thick fragments of basement membrane-like material piled up beneath endothelial cells and around perisinusoidal cells; transformation of perisinusoidal cells into cells with the characteristics of fibroblasts and myofibroblasts; decreased numbers of fenestrae for endothelial cells with processes often overlapping and attached with tight junctions; and rarefaction of Kupffer's cells. Expression of cellular and extracellular material abnormalities are related to the tumor differentiation. The study of these abnormalities may have implications in prognosis.

Abstract:
Extensive multiple neuropathies were observed in four patients after prolonged stay in intensive care units. Date of onset of the multiple disorders was difficult to determine due to disturbed consciousness of all patients during the first few weeks of intensive care: it was probably between the 10th and 30th days. Electrophysiological examinations in the 4 patients, and ultrastructural study of musculocutaneous nerve of leg in 2 cases, suggested an acute axonal lesion. All patients survived the causal affection which had justified prolonged intensive care, 3 recovering from the multiple neuropathy within 3 to 4 months, the last patient having marked neuromuscular sequelae. Several factors can be incriminated at the origin of this multiple neuropathy. Whereas retrospective studies allowed exclusion of a toxic, infectious or drug-related cause, severe nutritional deficiencies existed; proteins in all cases and vitamins in one patient despite enteral re-nutrition judged as satisfactory. Additionally, a role for a previous lesion of peripheral nerves from chronic hypoxia was possible in 2 cases as well as for a non-insulin dependent diabetes in one of these two patients. A rarely reported but probably not exceptional complication, diagnosis is assisted by early electrophysiologic exploration. Correction of nutritional disorders may require parenteral feeding exclusively, this possibly accelerating neurologic recovery, as proposed in the several rare studies reported in the literature.

Abstract:
Considerable progress has been made in the morphologic study of pituitary due to the availability of angioscan programs. An exceptional case is presented of a persistent intrasellar trigeminal artery associated with prolactinoma. Based on technological progress in CT scan imaging the place of angiographic explorations in the investigation of pituitary adenoma is reconsidered.

Abstract:
A single 2-h restraint stress reduces locomotion and increases defaecation of male rats placed in an open field 24 h later. After daily 2-h restraints for 5 days these effects were no longer observed. This adaptation was associated with enhanced sensitivity to the serotonin agonist 5-methoxy-N,N-dimethyltryptamine. Female rats were less affected by a single restraint but failed to adapt to the repeated stress procedure and did not exhibit enhanced sensitivity to 5-methoxy-N,N-dimethyltryptamine. Furthermore, females but not males killed 24 h after the final restraint period had decreased brain regional 5-hydroxyindoleacetic acid concentrations particularly in the frontal cortex. No sex differences in hypothalamic and striatal dopamine metabolism were observed. The above differences between male and female rats were unaffected by adult gonadectomy. Similar differences could be involved in the higher incidence of depressive illness in women.

Abstract:
Rats were trained to run on a horizontal treadmill for 2 h at 20 m/min. This activity considerably increased plasma free tryptophan (TRP) (+70%) but did not alter plasma total TRP levels and had little or no effect on plasma concentrations of the other large neutral amino acids (LNAAs) that compete with TRP for entry into the brain. Brain TRP levels increased by 80%. The only other brain LNAA to be affected by exercise was threonine, which rose moderately. The results indicate that increased plasma free TRP was specifically responsible for the increase of brain TRP after 2 h of exercise. Brain lysine was also increased whereas glycine, alanine, and gamma-aminobutyric acid were decreased. The differences between the present findings and those previously obtained following 2 h immobilization stress are discussed.

Abstract:
An investigation was made into the effects of running (1 h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.

Abstract:
Sinusoids ultrastructure was studied in a case of hepatocellular carcinoma developed in the non cirrhotic liver of a 40-year-old man. The surgical biopsy was perfusion-fixed with 1.5% glutaraldehyde. The number of Kupffer cells was very low. Endothelial cells with signs of hyperactivity were very irregular; digitations were often attached by numerous well identified junctional complexes to their own cell processes or to adjacent cell processes. Perisinusoidal cells without lipids resembled fibro-myofibroblasts. Discontinuous basement membranes underlaid endothelial cells and perisinusoidal cells. In addition numerous strands of short basement membranes segments were seen in the Disse space. Well organized bundles of collagen were not seen. The sinusoidal membranes of hepatocytes were flattened. The perfusion-fixation revealed to be a very useful technique in the identification of all these changes which have also been reported to some degree in benign liver cell adenoma and in cirrhosis; these two conditions are known to be associated with hepatocellular carcinoma.

Abstract:
Fusaric acid (FA) administration to the rats promoted one hour later a large decrease in plasma total tryptophan (TRP), without affecting either plasma free TRP or lipolysis, as measured by plasma non esterified fatty acid concentration. The previous change was associated with hypoinsulinemia, hyperglycemia and increased plasma corticosterone level. Regression analysis revealed a significant correlation between brain TRP and the percentage of plasma TRP which was free (i.e. unbound to albumin), both increased by FA injection. The increase in brain TRP promoted an increased brain serotonin synthesis, as measured by the enhanced brain and CSF 5-HIAA levels. Valine pretreatment, which blocks TRP entry into the brain, completely prevented FA-induced brain TRP and brain 5-HIAA increases. These results suggest that the increased brain serotonergic turnover following FA treatment was due to a peripheral action of the drug upon TRP disposition. The latter effect may be caused (i) by in vivo peripheral alterations in catecholaminergic metabolism and (ii) by FA chemical structure since in vitro experiments revealed that FA was able to displace TRP binding to albumin, thus increasing the plasma free TRP pool.

Abstract:
In the brains of colchicine-treated guinea pigs, antibodies directed against the C-terminal sequence of cholecystokinin octapeptide (CCK-8) and cross-reacting with gastrin, visualized a dense population of cell bodies in the arcuate nucleus, periportal nerve endings in the external layer of the median eminence and a few fibers in the neurohypophysis. In the adenohypophysis, at least the major part of corticomelanotrophs were labelled. Immunostainings are compared to those reported in the rat.

Abstract:
The effect of the dopamine-beta-hydroxylase inhibitor, fusaric acid (FA), on cerebrospinal fluid (CSF) homovanillic acid (HVA) was studied in pentobarbitone-anesthetized rats. Idazoxan, a selective alpha 2-antagonist, accentuated the FA-induced HVA elevation in CSF while alpha-methyldopa pretreatment prevented this effect of FA on the HVA level in CSF. These results could indicate that the rate of dopamine synthesis in noradrenaline neurons could be the main determinant of the FA-induced HVA elevation.

Abstract:
An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasma free Trp was decreased after 2 h of running. Liver Trp content rose only after 3 h of running, while liver unesterified fatty acid (UFA) concentrations remained unmodified. A comparison between food deprivation and running (both of which promote lipolysis) was performed. Running for 2 h affected to the same extent plasma Trp disposition when compared with 24 h food deprivation. Nevertheless, the ratio of brain Trp to plasma free Trp was decreased in the food-deprived rats, when compared to the runners. Nicotinic acid, which inhibits fat catabolism, completely abolished the plasma UFA increase induced by 1 h of running. The drug did not affect plasma free Trp, brain Trp, 5-HT or 5-HIAA but enhanced plasma total Trp level. Naloxone, an opiate antagonist, which decreased running-induced lipolysis, did not alter plasma Trp disposition. Desipramine, an antidepressant compound, affected only peripheral Trp concentrations of the runners. Plasma free and total Trp concentrations were increased in desipramine-treated runners, compared with saline-treated runners. In addition, desipramine increased the ratio of brain Trp to plasma free Trp of the runners. Brain 5-HT and 5-HIAA were increased in both desipramine-treated controls and runners. 9 The results suggest that running, which like food deprivatiQn accelerates lipolysis, increases brain Trp content and then 5-HT turnover. Comparison of these two physiological situations suggests that effectiveness of brain Trp entry is much more altered by fasting.

Abstract:
An investigation was made into the effects of hyperammonemia on the metabolism of brain serotonin (5-HT). The animal model used was the sparse fur (spf) mouse, which possesses an inborn error of the urea cycle, i.e. an abnormal form of ornithine transcarbamylase. Several indoles were measured in brain and plasma using liquid chromatography with electrochemical detection coupled to an u.v. detection (LCEC-u.v.). In the mutant mice, plasma total tryptophan (TRP) was higher when compared with the controls, while plasma free-TRP portion was unchanged. In these animals, brain TRP was increased whilst the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher in the hypothalamus and midbrain. Experiments with NSD-1015 (100 mg/kg i.p.) indicated that the 5-hydroxytryptophan (5-HTP) synthesis rate was increased in the hyperammonemic mice. Pargyline experiments (100 mg/kg i.p.) confirmed the enhanced brain 5-HT turnover rate in the spf mice. In addition, these experiments led to the conclusion that hyperammonemia does not affect the various rate constants. After administration of NSD-1015, TRP level slightly increased in the spf mouse brains, while it was stationary in those of the controls. This result could indicate an increased activity of hepatic TRP-pyrrolase in the hyperammonemic mice. Valine (VAL) administration (200 mg/kg i.p.) reduced brain TRP content in the two kinds of mice, but its effect was of shorter duration in the spf when compared with the control. Comparison of brain tryptamine level indicated a slight but not significant increase in the mutant mice. The data reported here indicate that hyperammonemia may affect peripheral TRP metabolism with consequences upon brain 5-HT synthesis, which could promote certain neurologic disorders.