The present study explores whether effects induced by amphetamine derivatives on striatal GABA cells might be connected with effects on dopamine (DA) metabolism. Methamphetamine (METH) and ...3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were administered to C57Black mice following a dosage regimen in which various doses of both drugs were injected i.p. at 2-h intervals. Neuronal inclusions produced under these experimental conditions were examined under electron microscopy. Drugs reducing DA availability prevented inclusion formation; conversely we observed that increasing DA synthesis or impairing physiological DA degradation enhanced the number of inclusions. The present study indicates that the presence of extracellular striatal DA is essential for the production of subcellular alterations induced by amphetamine derivatives. This is in line with a recent hypothesis connecting striatal DA release with degeneration of striatal GABA neurons.
The effect of repeated stress (1 h of daily immobilization for seven consecutive days) on the adrenal cortex of young adult male albino rats was evaluated by morphohistochemical methods and plasma ...assays; at the same time, testes and major salivary glands, as steroid-producing and -depending organs, respectively, were examined. Morphological and histochemical changes were found in the adrenal cortex, testis and submaxillary gland, though varying in degree and extent depending on the gland examined. Corticosterone and progesterone plasma levels increased, in agreement with the lipid depletion observed in the zona fasciculata, while testosterone and androstenedione decreased, as confirmed by the less marked enzymatic activity in the Leydig cells. The study thus proves that repeated stress, even of temporary duration, is able to influence directly or indirectly the morphofunctional state of the three examined glands, suggesting a functional linkage.
Noise exposure causes changes at different levels in human organs, particularly the cardiovascular system, where it is responsible for increasing heart rate, peripheral vascular resistance, and blood ...pressure. In this study, we evaluated the effect of noise exposure on DNA integrity and ultrastructure of rat cardiomyocytes. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage, accompanied by swelling of mitochondrial membranes, dilution of the matrix, and cristolysis. These alterations were concomitant with increased in situ noradrenaline levels and utilization. Genetic and ultrastructural alterations did not decrease 24 hr after the cessation of the stimulus. An elevated oxyradical generation, possibly related to altered sympathetic innervation, is hypothesized as responsible for the induction and persistence of noise-induced cellular damage.
In response to a stressful stimulus, there is a marked activation of the hypothalamic-pituitary-adrenal axis leading to a release of adrenocorticotropic hormone. This, in turn, acts on the zona ...fasciculata of the adrenal cortex to increase corticosterone plasma levels. Given the frequency of chronic intermittent noise exposure in man, we selected loud noise to evaluate concomitant changes in the ultrastructure of the adrenal cortex and corticosterone release. Following chronic (21 days, 6 h per day) loud white noise exposure (100 dBA, 0-26 KHz), we found the zona fasciculata to be most sensitive to time-dependent ultrastructural changes. These consisted of modifications in cell compartments involved in hormone synthesis and release. On the other hand, we found a progressive increase in corticosterone plasma levels which reached a plateau 9 days after noise exposure. The significance of these changes, in relation to phenomena like sensitization to repetitive stress, are discussed. Furthermore, the present data suggest that chronic loud noise exposure might potentially lead to endocrine dysfunctions.
The possibility of a pH-controlled drug release mechanism applying to silicone microspheres containing nicotinamide (NAM) and Polycarbophil (PCP), a pH-sensitive hydrogel, is evaluated. NAM-medicated ...PCP in the 4:1 PCP-NAM wt ratio is dispersed, at the 20% or 40% concentration, in silicone in the form of osmotically active particles of around 15
μm mean volume diameter, and encapsulated in microspheres in the 105–710
μm size range by a modified emulsion vulcanization technique, with a 100% entrapment efficiency. The external and internal morphology of microspheres, and the size distribution of PCP-NAM particles dispersed therein are evaluated by scanning electron micrography. Microspheres are eluted 9 h with simulated GI fluids (pH 1.2–7.4). Assessment of the time exponent characterizing the release kinetics, together with release and swelling data from planar matrices of same formulation as the microspheres, substantiate the following release mechanism. Due to their small size, the osmotically active particles have a limited ability to crack the silicone polymer and interconnect upon swelling, so the hydrogel route of release is of a minor relevance, and so is the hydrogel pH-sensitivity. Drug release is mainly governed by partitioning-diffusion in the silicone continuum of microspheres, therefore it is pH-independent and the time exponent is close to the value typical of Fickian release. It is concluded that encapsulation of hydrogel particles of larger size is a necessary condition for a pH-controlled release pattern.
The present study was performed to examine the effect of varying duration of noise exposure on rat adrenal gland. Animals were exposed to noise for 1, 6 and 12 h continuously and the sections ...obtained from exposed rats were compared to those from corresponding controls. No significant ultrastructural changes were found in the zona glomerulosa, while mitochondria of the zona fasciculata showed matrix dilution and cristolysis after 1 and 12 h of noise stress. At all exposure times examined, the zona reticularis exhibited areas of diluted cytoplasm, disarranged endoplasmic reticulum, membrane vestigia and some altered mitochondria. Diluted cytoplasmic areas appeared in noradrenaline- and adrenaline-storing cells after 6 and 12 h of exposure, respectively. Our findings indicate that each zona of the adrenal cortex and the two cell types of adrenal medulla show a differential reaction to noise stress.
: We have studied striatal dopamine (DA) metabolism in
monoamine oxidase (MAO) B‐deficient mice using brain microdialysis. Baseline
DA levels were similar in wild‐type and knock‐out (KO) mice. ...Administration of
a selective MAO A inhibitor, clorgyline (2 mg/kg), increased DA levels and
decreased levels of its metabolites in all mice, but a selective MAO B
inhibitor, l‐deprenyl (1 mg/kg), had no effect. Administration of 10
and 50 mg/kg l‐DOPA, the precursor of DA, increased the levels of
DA similarly in wild‐type and KO mice. The highest dose of l‐DOPA
(100 mg/kg) produced a larger increase in DA in KO than wild‐type mice. This
difference was abolished by pretreating wild‐type mice with
l‐deprenyl. These results suggest that in mice, DA is only metabolized by MAO A under basal conditions and by both MAO A and B at high concentrations. This is in contrast to the rat, where DA is always metabolized by MAO A regardless of concentration.
In our previous study we described a bilateral-macroscopic and structural dimorphism of young rat exorbital lacrimal gland (Loewenthal's gland), which was the probable cause of the bibliographic ...discrepancies in the entity and the onset of its sexual dimorphism. Relevant literature also reported sex-dependent alterations in gland structure during senescence. The present study aims to carry out a comparative analysis on age-dependent changes in glands of both sides from male and female rats, using histological, histochemical and transmission electron microscopy, to evaluate whether the gland bilateral-macroscopic and structural dimorphism might influence the kind of alterations which occur in senescence. Our findings indicate that the macroscopic and structural side-specific dimorphism is not so evident in comparison with young rats. The side-specific dimorphism is evident only in male rats, in which the roundish gland appears to be more Sudan-positive in comparison with the ellipsoidal gland. The gland bilateral-macroscopic and structural dimorphism, although more evident in comparison with young animals, does not seem to influence these kinds of alterations due to senescence, a time-window in which we still observed some sexual differences also in more aged rats.
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R)-Apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson’s disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in ...specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson’s disease.
This study represents a further contribution to our knowledge about the structure of Loewenthal's gland. There are several divergences in the available literature on the topic, concerning both the ...histological and ultrastructural findings. However, in these studies, the authors did not take into account the potential influence of a putative side-dependent dimorphism previously reported by us. We therefore carried out histological and electronmicroscopic observations specifically aimed at evaluating the importance of the gland shape for its structure. In particular, in male albino rats aged 70–120 days, we compared the structure of the left and right glands. Depending on the side undergoing morphological investigation, we observed differences in the acini, cells, nuclei, endoplasmic reticulum, Golgi apparatus and granular content. Apart from slight individual differences, we found that structural variations were most frequently observed in glands displaying a more evident macroscopic side-specific dimorphism. Our findings demonstrate that several conflicting data in the literature dealing with the structure of Loewenthal's glands might be explained by the morphofunctional side-dependent dimorphism of the organ.
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