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L Martini

Publications and source records attributed to L Martini.

At least 127 records · Page 7Linked to original sources
PubMed1993

In vivo experimental models on the evaluation of haemoperfusion.

We described some experimental models that were performed in rabbits and in swine in order to evaluate the efficacy of haemoperfusion treatment in hypochloremic alkalosis, uraemia and cytotoxic drug poisoning. In all the models, an extracorporeal circuit was used constituted mainly by a hematic sampling line and a cartridge, containing an anion exchange resin. Access to the blood stream was achieved by isolation and catheterization of the vessels either of the neck or of the leg, or both. The experimental model for the evaluation of haemoperfusion in hypochloremic alkalosis was carried out in rabbits by a pyloric stenosis because its size and weight are similar to new-born humans and its stomach is a simple monogastric one. The hypochloremia and alkalosis were achieved in only 4 hours. The other two experimental models were carried out in pigs because, in these cases, it was better to choose a large size animal with a nutritional similarity to humans, and with the capability to produce a stable chronic renal failure. The pigs were submitted to a bilateral ureter ligature to create a chronic renal failure or to a bilateral renal vessel ligature to avoid the physiologic precipitation of some drugs in renal tubules.

Alkalosis↗
PubMed1993

Adhesion molecule profile and malignancy of melanocytic lesions.

The ability of melanoma cells to metastasize is largely dependent upon cell surface molecules that mediate cell-matrix and cell-cell interactions. Our aim was to investigate the expression of such molecules (adhesion molecules) on tissue sections of a series of melanocytic lesions in different stages of tumour progression. Four common naevi, four congenital naevi, four dysplastic naevi, three Spitz naevi, 20 primary melanomas and 15 metastatic melanomas were tested with an alkaline phosphatase/anti-alkaline phosphatase technique and a panel of monoclonal antibodies directed toward different alpha subunits of VLA receptors, beta 1, VNR-alpha and beta 3 subunit, and CD44 hyaluronate receptor. Only metastatic melanomas expressed the alpha 4 subunit, and only thick primary melanomas and metastases expressed the beta 3 subunit. The alpha 6/beta 1 chain was expressed at significantly higher levels on benign lesions, and a trend towards increased expression of alpha 2 and alpha 3 subunits was found in malignant versus benign lesions. Our results show that the pattern of integrin expression changes in melanocytic lesions along with malignant transformation.

Antibodies, Monoclonal↗
PubMed1993

Ageing of the neuroendocrine system in the brain of male rats: receptor mechanisms and steroid metabolism.

The work described in this article gives information on the effects of ageing on the hypothalamo-pituitary-testicular axis in rats. The hypothalami of young and old male rats contain similar amounts of luteinizing-hormone-releasing hormone (LHRH); when perifused in vitro they release comparable amounts of LHRH under basal conditions and in response to K+. The addition of an LHRH analogue to the perifusion medium blocks the release of LHRH induced by K+ from the hypothalami of young and old male rats, indicating that the ultrashort feedback mechanism controlling LHRH release functions normally in aged male rats. Ageing also exerts important effects on the density of mu- and kappa-opioid receptors in the brain. The number of hypothalamic mu-opioid receptors was significantly decreased in aged animals; a replacement treatment with testosterone does not reverse this decrease, indicating that the decline of hypothalamic mu receptors and of serum titres of testosterone in old rats are independent phenomena. The number of kappa-opioid receptors in the brain increases in the amygdala and in the thalamus with ageing. Apparently ageing does not influence the number of delta receptors in any of the brain areas investigated. The number of pituitary LHRH receptors decreases in old animals, which might explain the low serum concentration of gonadotrophins in aged rats caused by an inadequate response of the pituitary to hypothalamic LHRH. The impaired secretion of testosterone in aged male rats is accompanied by an increase in the number of testicular LHRH receptors, indicating that the intratesticular mechanisms controlling testosterone release also undergo significant alterations during ageing. The rate of conversion of testosterone to dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) is the same in the hypothalami of young and old rats. However, the yields of DHT obtained from the pituitaries of aged male rats are significantly lower than those recorded in the pituitaries of young animals. These results show that the enzymes necessary for metabolizing testosterone via the 5 alpha-reductase pathway are maintained both in the hypothalamus and in the anterior pituitary of aged male rats. However, the 5 alpha-reductase activity of the anterior pituitary of senescent animals appears to be lower than that in the younger controls.

Aging↗
PubMed1993

Studies on varicocele. II. The inhibin secretion.

In this paper a previous interpretation given by the authors concerning one of the ways varicocele can affect fertility is confirmed. Moreover, it is definitely demonstrated that the high temperature stimulates inhibin secretion (and probably the testosterone-estradiol conversion) in the Sertoli cells, while the somatomedin secretion in vitro seems to be unaffected. It means that the action of the temperature on the germinal cells seems to be mediated by the pathway: inhibin (plus estradiol)-->pituitary-->FSH. Inhibin in the Golgi complex of Sertoli and germinal cells has been detected by electron microscopical immunocytochemical techniques.

Adult↗
PubMed1992

Aromatase activity in cultured brain cells: difference between neurons and glia.

At the level of the central nervous system (CNS) of several mammalian and non-mammalian species, estrogens may be intracellularly formed from circulating androgens through the action of the aromatase complex. Estrogenic steroids play a crucial role in organizing and directing certain behavioral and neuroendocrine responses both during the fetal/neonatal life and in adulthood. Biochemical and immunocytochemical studies have shown that the aromatase is particularly concentrated in CNS areas involved in the control of reproductive functions, such as the hypothalamus, the preoptic area and the limbic system; despite this large body of evidence, the exact cellular localization of this enzymatic complex within the different cell populations of the brain is still uncertain. In the experiments described here, the presence of the aromatase has been evaluated in the two main cellular components of the brain: the neurons and the glia. In these experiments, cultures of neurons obtained from the brains of 14-15-day-old rat embryos, mixed glial cells from 1-day-old rats and type 1 astrocytes derived from cultured glial cells, have been utilized. The aromatase has been also evaluated in oligodendrocytes isolated from adult male rat brain by density gradient ultracentrifugation. The aromatase activity has been assayed by an 'in vitro' radiometric method which quantifies the production of tritiated water from [1 beta-3H]-androstenedione as an index of estrogen formation. The validity of the method has been verified both on the placental microsomes and on rat hypothalamic tissue, in which the actual formation of estrogens has also been measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Intracellular signalling systems controlling the 5 alpha-reductase in glial cell cultures.

Glial cells are able to metabolize testosterone into DHT through the action of the enzyme 5 alpha-reductase. DHT may be further processed to 3 alpha-diol by the 3 alpha-hydroxysteroid-dehydrogenase. The aim of this study was to analyze if a modulation of two second messenger systems might be able to modify the 5 alpha-reductase and the 3 alpha-hydroxysteroid-dehydrogenase activities present in glial cells. To this purpose, the formation of DHT has been measured in rat glial cell cultures after different time of exposure to TPA, 4 alpha-Ph, an active and an inactive phorbol ester respectively, and 8-Br-cAMP. The results obtained indicate that the formation of DHT is not modified by the addition of phorbol esters. On the contrary, a statistically significant increase of 5 alpha-reductase activity, over control levels, has been observed after 6, 12, and 24 h of incubation with 8-Br-cAMP (10(-3) M). The effect of the cAMP analogue appears to be specific for the 5 alpha-reductase, since the 3 alpha-hydroxysteroid-dehydrogenase did not show any variation after exposure to the drug. In conclusion, the present data suggest that proteinkinase A (PKA) might be involved in the control of the 5 alpha-reductase in glial cells. It is postulated that nervous inputs utilizing cAMP as the second messenger might modify the activity of this enzyme in glial cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Binding characteristics of delta opioid receptors in different regions of the brain of young and old male rats as studied with the highly selective ligand [D-Pen2-D-Pen5] enkephalin.

The present experiments were performed to study the binding characteristics of delta opioid receptors in membrane preparations obtained from the brain of adult male rats, and to analyze whether aging modifies these binding parameters. The binding characteristics of delta opioid receptors were evaluated on membrane preparations derived from dissected brain regions (hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex) collected from male rats of 3 and 24 months of age; the highly selective ligand 3H-[D-Pen2-D-Pen5] enkephalin (3H-DPDPE) was used. The results obtained in young rats show that the distribution of delta opioid receptors is different in the various brain areas examined; these receptors appear to be maximally concentrated in the frontal poles, anterior and posterior cortex; lower concentrations were found in the other structures considered. Kd (dissociation constant) for the delta sites was found very similar in all areas. The distribution of delta opioid receptors in the brain of 24-month-old rats was similar to that observed in young animals; this result was surprising in view of the fact that aging modifies the number of other types of brain opioid receptors (mu and kappa).

Aging↗
PubMed1992

Is the 5 alpha-reductase-3 alpha-hydroxysteroid dehydrogenase complex associated with the myelin in the peripheral nervous system of young and old male rats?

The formation of the 5 alpha-reduced metabolites of testosterone, 5 alpha-androstan-17 beta-ol-3-one (dihydroxytestosterone, DHT) and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol) was evaluated in sciatic nerve fragments and homogenates and in the myelin purified from the sciatic nerve of adult (60-90-day-old) male rats. The effects of aging on the metabolism of testosterone in the sciatic nerve was also evaluated using 20-month-old animals. In the sciatic nerve, tissue homogenization and myelin purification are associated with a marked decrease in the 5 alpha-reductase activity; these data do not appear to be consistent with a possible association of the enzyme with myelin membranes, as it occurs in the CNS. However, the results may be subject to other interpretations which are presented in the discussion. The formation of 3 alpha-diol is higher in sciatic nerve fragments than in homogenates or in the purified myelin. This occurs when testosterone is used as the substrate. In aged animals, the same pattern is observed but at a lower level. In the incubations in which the formation of 3 alpha-diol was evaluated using DHT as the substrate in fragments, homogenates and purified myelin of the sciatic nerve of either adult or old animals, it was found that the yields of this metabolite are higher than those obtained following incubation with testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

The 5 alpha-reductase in the brain: molecular aspects and relation to brain function.

All the classes of hormonal steroids physiologically produced in the body (androgens, estrogens, progestagens, and corticosteroids) are able to exert important effects on the brain, but the mechanisms of their actions are not always well understood. Steroids may interact with intracellular receptors to activate the genome, but some of their effects are probably extragenomic and involve interactions with cellular membranes. Moreover, not all the steroids act always in their native molecular form; a large group of them must actually be transformed into "active" metabolites. This may occur at the level of their respective target structures. For example, androgens are metabolized in the brain into estrogens and into 5 alpha-reduced androgens, like 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone; DHT) and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). Progesterone, and possibly corticosteroids, may also be transformed into their corresponding 5 alpha-reduced metabolites. Also the cellular target (neurons and/or glial cells) of the hormonal steroids in the brain is not always clear. This review analyzes in detail one of the two major enzymatic systems that transform steroids in the brain, namely the 5 alpha-reductase-3 alpha-(3 beta)-hydroxysteroid dehydrogenase pathway. An active 5 alpha-reductase-3 alpha-hydroxysteroid dehydrogenase system is widely distributed in practically all CNS structures in all phases of development. In the brain, this enzymatic system is not regulated by castration or sex steroid administration; furthermore, neural inputs seem to be ineffective at the hypothalamic level. A recent interesting finding is the presence of high concentrations of the 5 alpha-reductase in the white matter. This probably is due to the fact that the white matter is particularly rich in myelin membranes, with which the enzymatic activity appears to be associated. An active 5 alpha-reductase activity has also been shown to be present in peripheral myelinated nerves. The localization in myelin membranes may suggest a possible involvement of 5 alpha-reduced metabolites of the different steroids in the process of myelination. The presence of the 5 alpha-reductase was analyzed in neurons, astrocytes, and oligodendrocytes isolated from the brains of male rats, as well as in neurons and glial cells grown in culture. Neurons appear to be more active than glial cells in converting testosterone into DHT. Only neurons possess aromatase activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Androgen metabolism in the brain.

The paper summarizes the most recent views on androgen metabolism in the brain. In particular it will be shown that: (1) the enzyme 5 alpha-reductase is particularly concentrated in the white matter; (2) 5 alpha-reductase is also present in the myelin; 5 alpha-reductase is present in higher concentrations in neurons (isolated or cultured) that in glial cells (astrocytes and oligodendrocytes); (4) only neurons possess the capability of aromatizing androgens to estrogens; and (5) a possible role of steroid metabolism in the control of the process of myelinogenesis is suggested.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1991

Comparison of monoclonal immunocytochemical and immunoenzymatic methods for steroid receptor evaluation in breast cancer.

The production of monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PR) has permitted the development of the enzyme immunoassay (EIA) and immunocytochemical assay (ICA) for steroid receptor determination. The results obtained with these two techniques, using the same monoclonal antibodies, were compared in a large series of breast carcinomas (187 for ER and 100 for PR). The correlation between these methods was significant for ER (rs = 0.54) and PR (rs = 0.55) (P less than 0.001) but was lost when the receptor concentrations determined by EIA were less than or equal to 15 and less than or equal to 30 fmol/mg protein for ER and PR, respectively. When these values are considered as cutoffs, the concordance between the two methods was 84.5% for ER and 73% for PR. An analysis of discordant results revealed that low epithelial cellularity generally was present in ICA-positive, EIA-negative specimens, whereas only focal positivity with ICA, or positivity of only normal peripheral mammary ducts and lobules, frequently was found in ICA-negative, EIA-positive tumors. In conclusion, there is good correlation between the results obtained by EIA and ICA methods for detection of ER and PR. The authors suggest that biochemical and histochemical methods for steroid receptors could be considered complementary and used together for the analysis of breast cancer.

Adult↗
PubMed1991

[AIDS and myasthenia: an uncommon association].

A 18 year-old soldier, heroin-addict, presented with the association of myasthenia gravis and HIV infection with a specific subacute encephalopathy. To our knowledge, it is the second reported case. This association may result from an immune dysregulation due to nonspecific thymic modifications, which has been reported in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

5 alpha-reductase activity in isolated and cultured neuronal and glial cells of the rat.

The distribution of the 5 alpha-reductase, the enzyme which converts testosterone into its 'active' metabolite dihydrotestosterone (DHT), has been studied in neurons, astrocytes and oligodendrocytes isolated from the brain of male rats by density gradient ultracentrifugation and in neurons and glial cells grown in cultures. Purity of cellular preparations was examined by electron and light microscopy. Purified neurons, astrocytes and oligodendrocytes, obtained from the brain of adult male rats, are all able to form DHT from testosterone and consequently possess a 5 alpha-reductase activity. Among the 3 cell types studied, neurons appear to be more active than oligodendrocytes and astrocytes. Moreover, between the two population of glial cells, the oligodendrocytes seem to possess a slightly higher enzymatic activity than that present in the astrocytes. Neurons appeared more active in metabolizing testosterone than glial cells also in cell culture experiments. It is presently believed that the 5 alpha-reduction of testosterone to DHT provides one of the mechanisms through which the hormone becomes effective in the CNS. This is supported by the present findings, which indicate that neurons are the cell population in which the 5 alpha-reductase is more concentrated. However, the presence of a considerable 5 alpha-reductase activity in glial cells indicates that also non-neuronal cells might participate in androgen-mediated events occurring in the brain.

Animals↗
PubMed1990

Kinetic properties of the 5 alpha-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain.

The 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5 alpha-reductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5 alpha-reductase has a higher activity in immature animals. This study was performed in order to verify whether the differences in the 5 alpha-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60-90-day-old), immature (23-day-old), and aged (greater than 20-month-old) male rats. The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 +/- 0.2, 2.72 +/- 0.73 and 3.83 +/- 0.49 microM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 +/- 5.54), in the white matter (19.57 +/- 2.36) and in the cerebral cortex (6.47 +/- 1.03 ng/h/mg protein) of adult animals have been found to be consistently different. Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 +/- 0.11 and 3.39 +/- 0.75 microM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 +/- 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 +/- 5.54); a Vmax (34.31 +/- 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Testosterone metabolism in peripheral nerves: presence of the 5 alpha-reductase-3 alpha-hydroxysteroid-dehydrogenase enzymatic system in the sciatic nerve of adult and aged rats.

Previous reports from this laboratory indicate that the 5 alpha-reductase, the enzyme which converts testosterone into its "active" metabolite 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT) is highly concentrated in the white matter structures of the CNS, which are mainly composed of myelinated fibers. No studies have been performed up to now, in order to evaluate the possible presence of the 5 alpha-reductase activity in peripheral myelinated nerves. To this purpose the 5 alpha-reductase activity has been evaluated in the sciatic nerve of the rat and compared to that present in the cerebral cortex and in the subcortical white matter, a central structure mainly composed of myelinated fibers. The study has been performed in normal adult male rats (60-90-day-old) and in aged (20-month-old) animals. The data obtained in 60-90-day-old animals indicate the presence of an active metabolism of testosterone at the level of the sciatic nerve. In this structure, testosterone is actively transformed into DHT and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); in the sciatic nerve, the formation of DHT is equal to that found in the subcortical white matter and higher than that found in the cerebral cortex. Moreover, at variance with what happens in CNS structures, where 3 alpha-diol is produced only in small amounts, in the sciatic nerve this metabolite is produced in amounts similar to those of DHT. The study in aged rats has shown that in the sciatic nerve, the formation of DHT and particularly that of 3 alpha-diol are much lower than in younger animals. No age-related variations in the 5 alpha-reductase activity in the cerebral cortex and in the subcortical white matter have been observed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro.

Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6,Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered.

Aging↗