Biomedical subjects
Publications and source records attributed to N Battistini.
Data obtained in this preliminary study show that in patients chronically treated either with Chlorimipramine (n = 6) or with Chlorpromazine (n = 2), significant amounts of the corresponding Nor1- and Nor2-metabolites were detected in plasma. The role of these metabolites in the overall therapeutic effect is under investigation.
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By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.
Chronic ganglioside treatment (10 mg/kg, i.p.) using the molecular species with only one neuroaminic acid residue (GM1) given together with haloperidol (0.3 and 5 mg/kg, i.p.) once daily in male rats, counteracted the haloperidol-induced increase in the number of [3H]spiperone binding sites in striatal membranes when the low dose of haloperidol, but not the high dose, was administered. The present results therefore indicate that chronic GM1 treatment can partially counteract the increase in the number of dopamine receptors having a high affinity for neuroleptics (D2 type) induced by chronic haloperidol treatment in striatal membranes, and therefore may also partially counteract the development of neuroleptic-induced dopamine receptor supersensitivity.
Weak to strong gastrin releasing peptide--bombesin (GRP-Bn)-like immunoreactivity was found in fine varicose nerve terminal systems of low to high densities in several parts of the CNS. The highest densities of strongly immunoreactive terminals were found in the marginal layer and in the substantia gelatinosa of the spinal cord, and in parts of the nuc. tractus spinalis nervi trigemini. Morphometrical analysis in the spinal cord demonstrates that GRP-BN-like-immunoreactive and substance P (SP), but not somatostatin (SS)-immunoreactive nerve terminals strikingly codistribute. Coexistence of SP and GRP-BN-like immunoreactivities was demonstrated in trigeminal and spinal ganglion nerve cells. Thus, GRP-BN-like immunoreactivity may coexist with SP in certain SP-immunoreactive nerve terminal systems.
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Cases of polyneuropathy due to exposure to industrial solvents have been studied at several shoe factories in the province of Siena. After the screening of 654 employees 98 verified cases were detected. Of these, 16 were rated as moderate to severe, 45 as mild, and 37 were minimally involved but with characteristic electrodiagnostic abnormalities. Follow-up study in 53 patients showed that neurological signs and symptoms as well as electrodiagnostic abnormalities continued for years in several patients. In addition, after a year's observation, some patients showed signs of central nervous system dysfunction such as spasticity of the lower limbs and increased deep tendon reflexes. High percentages of commercial n-hexane were found in all the samples of glues and solvents collected from home-workers and from factories where cases of polyneuropathy occurred.
Subacute treatment with toluene leads to a dose-related reduction of affinity in the [3H]spiperone binding sites labeling striatal dopamine (DA) receptors of the D2 type and cortical [3H]5-hydroxytryptamine (5-HT)-binding sites. It is suggested that these results represent a down regulation of activity at striatal DA and cortical 5-HT synapses, since they now may operate at higher concentrations of transmitters. The reduced affinity may be caused by the physicochemical properties of toluene leading to changes in membrane fluidity and thus in the regulation of DA and 5-HT receptors in the local circuits of the striatum and the dorsal cerebral cortex.
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Explore the source record for details and available documents.
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Subacute exposure of rats to varying concentrations of toluene vapours leads to increases of amine levels and turnover in several types of hypothalamic noradrenaline nerve terminal systems. Furthermore, the exposure of toluene in concentrations ranging from 80-3000 ppm and benzene (1500 ppm) produced differential effects on dopamine and noradrenaline turnover within various parts of the hypothalamus. These regions are involved in neuroendocrine regulation and disturbances in the secretion of prolactin were demonstrated after exposure to toluene.
A double-blind clinical trial was carried out involving 26 hospitalized, depressed patients who were randomized into two groups. Patients in each group received chlorimipramine (50 mg/day), combined with L-5-HTP (300 mg/day) in Group A, and with placebo in Group B. The trial lasted 28 days. Two Group B patients dropped out. All the patients were evaluated by HRSD each week, and by ZDSI and CGI at the beginning and end of treatment. Several statistical analyses of the mean HRSD scores of each item presenting initial positive response and of ZDSI scores for both reactive and endogenous depression were performed, using Student's t-test. To evaluate the efficacy of the chlorimipramine +L-5-HTP combination versus control therapy the Mann-Whitney test was applied to the reduction in HRSD scores, showing 0.05 significance. The results for both types of pathology were quantitatively and qualitatively more positive for Group A than for Group B. Cluster analysis of HRSD item scores alone and between this scale and ZDSI, according to Carrol's correlation method for the symptoms of the cluster (mood, anxiety and somatic symptoms), was carried out to confirm the above results.
A theoretical model is introduced by which the tolerance to the increase in the dopamine turnover rate produced by neuroleptics both at cell body and nerve terminal levels is analyzed according to the principles of control theory. Thus, it is shown that tolerance development does not rule out the possibility that the therapeutic action of neuroleptics may be exerted at the level of that dopamine projection.
The rates of local cerebral glucose utilization have been measured in normal conscious and hypnotized rabbits by the [14C]deoxyglucose method. In control rabbits the rates vary widely throughout the brain, with the values in gray matter broadly distributed around an average which is about 3 times greater than that of white matter. The higher values area in structures of auditory system (superior olive, inferior colliculus, auditory cortex). Animal hypnosis reduces the rates of glucose utilization in all structures of the rabbit brain, particularly in the caudate nucleus, putamen and sensory and motor cortices.
The effect of pentoxifylline on cerebral blood flow (CBF) was studied with the intravenous 133Xe clearance technique in eleven patients with chronic cerebrovascular disease. Pentoxifylline was administered orally at a dose of 1200 mg/day over a period of 30 days (eight patients) or by intravenous infusion of 100 ml saline containing 400 mg of the drug in 1 hour (three patients). CBF was measured before and after pharmacological treatment. CBF was found to be significantly increased by both acute and chronic administration of pentoxifylline.
On the basis of findings obtained by means of both traditional and modern tomographic techniques, Authors discuss changes of cerebral blood flow (CBF) and metabolism in acute cerebral ischemia and chronic cerebral circulatory insufficiency. Drug effects on cerebral circulation and metabolism are examined and experiences with pentoxifylline, substance provided with haemorheologic action, are reported.