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Biomedical subjects

V Costa

Publications and source records attributed to V Costa.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mitochondrial superoxide dismutase is essential for ethanol tolerance of Saccharomyces cerevisiae in the post-diauxic phase.

This work reports the role of both superoxide dismutases-CuZnSOD (encoded by SOD1) and MnSOD (encoded by SOD2)-in the build-up of tolerance to ethanol during growth of Saccharomyces cerevisiae from exponential to post-diauxic phase. Both enzyme activities increase from the exponential phase to the diauxic shift and from the diauxic shift to the post-diauxic phase. The levels of mRNA-SOD1 and mRNA-SOD2 increase from the exponential phase to the diauxic shift; however, during the post-diauxic phase mRNA-SOD1 levels decrease while mRNA-SOD2 levels remain unchanged. These data indicate the existence of two regulatory mechanisms involved in the induction of SOD activity during growth: synthesis de novo of the proteins (until the diauxic shift), and post-transcriptional or post-translational regulation (during the post-diauxic phase). Ethanol does not alter the activities of either enzyme in cells from the diauxic shift or post-diauxic-phases, although the respective mRNA levels decrease in post-diauxic-phase cells treated with ethanol (14% or 20%). Results of experiments with sod1 and sod2 mutants show that MnSOD, but not CuZnSOD, is essential for ethanol tolerance of diauxic-shift and post-diauxic-phase cells. Evidence that ethanol toxicity is correlated with the production of reactive oxygen species in the mitochondria is obtained from results with respiration-deficient mutants. In these cells, the induction of superoxide dismutase activity by ethanol is low; also, the respiratory deficiency restores the capacity of sod2 cells to acquire ethanol tolerance.

Enzyme Induction↗
PubMed1996

The molecular defences against reactive oxygen species in yeast.

There is rapidly expanding interest into the protective systems against reactive oxygen species (ROS) in the eukaryotic cell, now that the links between oxidative damage, various disease states, and ageing, are firmly established in higher organisms. Yeast molecular genetics should be able to provide powerful insight into these mechanisms; this potential is now starting to be exploited. A number of primary antioxidant activities and systems of metal-ion homeostasis or detoxification have now been demonstrated to contribute to oxidative-stress protection in yeast. Also, evidence is emerging that the oxidative-stress response of this organism is complex, involving separate transcription-factor responses to peroxide, superoxide anion and metal ions.

Oxidative Stress↗
PubMed1996

Zinc content and distribution in the newborn liver.

The newborn liver is a proven model for the study of liver storage of copper and iron. We analyzed zinc concentration and distribution in the livers of newborns and infants using a systematic tissue-sampling technique. We studied 14 newborns of 26-41 weeks of gestation (WG). One stillborn, and three infants (52-90 days old). At autopsy, a longitudinal liver slice extending from the right to the left lobe was subdivided into 10 samples that were analyzed for zinc concentration by atomic absorption spectroscopy. The mean zinc concentration in the newborn liver was 639 micrograms/g of dry tissue (dt). A striking interindividual variability in zinc liver stores was observed; the hepatic concentration of the metal ranged from 300 to 1,400 micrograms/g dt. We found a correlation between zinc liver content and gestational age. In newborns of 27-32 WG, the hepatic zinc concentration was significantly higher (p < 0.01) than in newborns of 34-41 WG. Zinc stores decreased in the postnatal period; in the infant group, the mean liver zinc concentration was 148 micrograms/g dt. The analysis of zinc concentration in 10 blocks from each liver revealed a regular distribution of the metal, without significant differences between liver lobes. Our data show that the newborn liver can be considered an interesting model for the study of zinc storage, which appears to correlate inversely with gestational age. From a practical point of view, the observed regular distribution of zinc implies that, at least in this model, zinc content determined in a small liver sample is representative of zinc content in the whole liver.

Female↗
PubMed1995

Uneven hepatic iron and phosphorus distribution in beta-thalassemia.

BACKGROUND/AIMS: Determination of hepatic iron concentration is crucial in the evaluation of iron-storage disease. Iron content is normally determined in a part of a needle liver biopsy and the value obtained is considered to be representative of the iron concentration in the whole liver. To evaluate the reliability of this procedure, we studied iron distribution in the liver of two beta-thalassemic patients. Since the transport of intracellular iron is mediated by phosphates, we also studied the hepatic phosphorus distribution. METHODS: At autopsy, a liver slice extending from the left to the right lobe was divided into 51 and 49 samples, respectively. Each specimen was subdivided into two parts: one of them was paraffin-embedded and utilized for the histochemical detection of iron; the second part was analyzed for iron and phosphorus content by induced coupled plasma atomic emission spectroscopy. RESULTS: The histological picture of both livers was characterized by portal and periportal fibrosis associated with iron storage of different degree, without cirrhosis. The mean iron concentration of the liver was 20,631 +/- 4903 micrograms per g of dry tissue (micrograms/g dt) and 13,901 +/- 1976 micrograms/g dt, respectively. A striking variability in iron content between samples was also found: iron concentration ranged from 11,537 to 32,347 micrograms/g dt in the first case and from 6257 to 16,493 in the second case. We even observed regional differences in iron concentration, with a preferential peripheral accumulation in both cases and a tendency of the left compartment of the liver to accumulate more iron in the first case. Histochemical analyses confirmed the uneven iron distribution even at the acinar level, showing iron mainly being stored in hepatocytes and Kupffer cells of zone 1 of the acinus, with decreasing amounts of iron in zones 2 and 3. The mean hepatic phosphorus concentration was 6662 +/- 1300 micrograms/g dt (range: 4348-9947) and 7502 +/- 986 micrograms/g dt (range: 5844-90,282), respectively. The regional distribution of phosphorus was similar to that observed for iron. A strict correlation between iron and phosphorus content was also observed. CONCLUSIONS: Our data show that: 1) iron and phosphorus are unevenly distributed in the beta-thalassemic liver, even in the non-cirrhotic stages; 2) a regional pattern of iron and phosphorus distribution is evident, characterized by higher concentrations at the periphery of the liver; 3) the observed uneven distribution of iron and phosphorus implies that their content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic iron concentration. Therefore, iron concentrations determined in a part of a needle liver biopsy should be interpreted with caution in monitoring the efficacy of the iron-chelating therapy in beta-thalassemic patients.

Adult↗
PubMed1995

Chemometric methods applied to an ICP-AES study of chemical element distributions in autopsy livers from subjects affected by Wilson and beta-thalassemia.

The concentrations of seven elements (Ca, Cu, Fe, Mg, P, S and Zn) in three autopsy livers (from two beta-thalassemic patients and one Wilson's disease patient) were determined by ICP-AES technique. At autopsy the three livers were subdivided into a large number of samples for a detailed study of the distribution of Fe and Cu, the accumulation of which characterizes the two diseases. In the same samples Ca, Mg, P, S and Zn concentrations were also determined in order to study significant variations or anomalous trends that could help identify these diseases. Our results generally show a good coincidence with literature data within the limits of sample variability. Based on Factor Analysis as well as Regression Analysis there is evidence of a high correlation between Fe and P contents in beta-thalassemia. The latter finding led us to propose tentatively an accumulation of Fe as a complex with P-containing molecules.

Adult↗
PubMed1994

Iron concentration and distribution in the newborn liver.

Recent observations on a correlation between fetal serum ferritin and gestational age, consistent with an increase in fetal iron stores during pregnancy, led us to study liver iron content in 22 human stillborns, newborns and infants of different gestational and postnatal age. At autopsy, a longitudinal liver slice was subdivided into ten blocks. Each sample was analyzed for iron content by atomic absorption spectroscopy. The mean iron concentration in the studied livers was 21.6 microM/g dry tissue (d.t.). A striking interindividual variability in iron content was observed: the hepatic concentration of the metal ranged from 3.3 to 64.4 microM/g d.t. No correlation was found between the hepatic iron concentration and gestational age or other clinical parameters of the patients studied. Moreover, the total storage iron of the liver did not appear to be correlated with the gestational age. The analysis of iron concentration in ten blocks in each liver revealed an irregular distribution of the metal. Lobar differences were observed, with a tendency of the left lobe to accumulate more iron than the right one. Furthermore, striking differences in iron content were found between adjacent liver samples, ranging in one instance from 4.5 up to 109.0 microM/g of dry tissue. Perls' stain for iron was positive in 7 out of the 22 livers examined, showing an irregular acinar distribution, with preferential periportal localization. Our data show that the newborn liver can be considered an interesting model for the study of iron storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

The nucleus basalis of Meynert of the human brain: a Golgi and electron microscope study.

The nucleus basalis of Meynert of normal brains, aged from 15 to 73 years was studied in Golgi preparations and in electron microscopy. The nucleus is composed of large triangular, polyhedral and bipolar cells which are intermixed with numerous small or medium-sized spiny neurons. All of the neurons form a dense three dimensional dendritic arborization, with numerous secondary and tertiary dendritic branches studded with spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spiny neurons and the large triangular and polyhedral neurons. The presynaptic axonic profiles are plenty of ellipsoid and round synaptic vesicles. Large presynaptic terminals are seen frequently surrounded by numerous dendritic spines forming synaptic glomeruli, in all the areas of the nucleus basalis of Meynert. An age depended decrease of the number of neurons was noticed affecting mainly the population of the spiny neurons. Although in senile and presenile dementias an impressive loss of the cholinergic neurons of the nucleus basalis was reported, in normal aging the large cholinergic neurons of the nucleus basalis seems to be intact, whereas the medium and small shaped spiny neurons are decreased in number suggesting that the GABA-ergic neurons are principally affected.

Adolescent↗
PubMed1994

Lack of relationship between hair lead levels and some usual markers (blood lead levels, ZPP, urinary ALA-D) in occupationally exposed workers.

Blood and hair samples collected from 54 male workers occupationally exposed to lead were assayed for this metal by graphite furnace atomic absorption spectrophotometry. Blood ZPP and urinary ALA-D were also determined for most subjects tested. Blood and hair lead concentrations (PbB and PbH) ranged from 100 to 770 ng/ml (10 to 77 micrograms/100 ml) (mean +/- SD: 384.6 +/- 143.4 ng/ml (38.46 +/- 14.34 micrograms/100 ml)), and from 3 to 243 ng/mg (mean +/- SD: 102.4 +/- 72.6 ng/mg), respectively. No correlation was observed between the PbH and PbB values, nor between PbH and ZPP or ALA-D values. Neither hair coloration nor subjects' age were related to PbH levels. Results are discussed in the light of the existing literature.

Adult↗
PubMed1994

Scanning electron microscopy of chronic hepatitis C. An OsO4 maceration study on human biopsies.

A study at the scanning electron microscope (SEM) on the liver changes in chronic hepatitis C was carried out in human needle biopsies from four patients. Intracellular structures were visualized by a novel modification of the OsO4 maceration method that allows to investigate human pathological specimens. At low magnification we observed both sinusoidal and hepatic cells alterations: sinusoids appeared occluded by lymphocytes, hypertrophic Kupffer cells, activated perisinusoidal cells, necrotic material and apoptotic bodies. Some hepatocytes showed ballooning, arrangement in rosettes, and structural changes related to apoptosis: cell rounding, detachment from neighbouring cells, clustering of cytoplasmic organelles and cell fragmentation. We also found periterminal, sinusoidal, and pericellular severe fibrosis, and bile duct damage of moderate degree. At higher magnification, after removing the intracellular matrix, all the intracellular structures appeared normal, except for focal dilatation of smooth endoplasmic reticulum. Our findings clearly demonstrate the usefulness of the OsO4 maceration method for the study of chronic hepatitis and of liver disease in general. Thank to this technique, in fact, SEM becomes a diagnostic tool complementary to light microscopy and transmission electron microscopy (TEM), for its unique ability to give both low magnification panoramic views and detailed high magnification 3D images of cell organelles.

Biopsy, Needle↗
PubMed1994

Immunohistochemical and genetic characterization of the M Cagliari alpha-1-antitrypsin molecule (M-like alpha-1-antitrypsin deficiency).

BACKGROUND: Genetic alpha-1-antitrypsin (AAT) deficiency may be due to defective secretion, intracellular degradation, or lack of synthesis. Defective secretion results in hepatocytic storage and liver disease. These two events occur only with the common deficiency variant, Z AAT, and with a few rare deficiency variants, called M-like. Hepatocytic storage of AAT (either Z or M-like) can be demonstrated in tissue sections by specific immunostaining with a polyclonal anti-AAT antibody, that recognizes all variants of AAT. A monoclonal antibody capable of selectively and exclusively reacting with Z AAT has been generated and successfully used in both serum and tissue studies. EXPERIMENTAL DESIGN: To determine whether a new M-like variant, M Cagliari, carries a mutation different from Z AAT, we have compared antigenic properties and DNA sequences of the two variants. Liver tissue sections from PiZ and PiM Cagliari patients were stained with both polyclonal anti-AAT and monoclonal anti-Z AAT antibodies. DNAs were polymerase chain reaction-amplified with AAT-specific primers and sequenced. RESULTS: Liver tissue sections from PiZ livers were positively stained with either the polyclonal or the monoclonal antibody. The PiM Cagliari liver sections reacted with the polyclonal antibody, but not with the monoclonal anti-Z AAT, thus indicating a difference in antigenicity from Z AAT. Accordingly, DNA analysis ruled out a Z mutation and revealed a microdeletion in exon II, identical with M Malton. CONCLUSIONS: A simple immunohistochemical assay based upon the application of both polyclonal and monoclonal antibodies represents a reliable test to distinguish Z and nonZ AAT deficiencies, thus assisting in the selection of cases worthy of more time-consuming analyses such as DNA sequencing. The same approach may be used for the characterization of as yet undefined PiM cases with AAT liver storage.

Adult↗
PubMed1993

Acquisition of ethanol tolerance in Saccharomyces cerevisiae: the key role of the mitochondrial superoxide dismutase.

Saccharomyces cerevisiae aBR10 cells are able to develop resistance to lethal ethanol concentrations (14%, v/v), by preexposure to a sublethal heat shock (37 degrees C) or ethanol stress (8%, v/v). Heat shock and 8% ethanol stress had no effect on the concentrations of glutathione [reduced (GSH) and oxidized (GSSG) forms] and on glutathione reductase and CuZn superoxide dismutase (SOD) activities, suggesting that the development of resistance to lethal ethanol concentrations is independent of these antioxidant defenses. In fact, a S. cerevisiae mutant, deficient in CuZnSOD, had an even higher ethanol tolerance, compared to the wild-type strain, and this mutation did not impair a further acquisition of ethanol tolerance. In contrast to CuZnSOD, the MnSOD activity seems to play a more important role in ethanol resistance. The MnSOD activity of the S. cerevisiae aBR10 cells increased upon exposure to heat shock or 8% ethanol. The higher tolerance to 14% ethanol in CuZnSOD deficient cells was also associated to a higher MnSOD activity, as compared to the aBR10 cells; this activity decreased during both stress pretreatments (while still higher than that observed in the wild-type strain). The results obtained suggest that maximum ethanol tolerance is attained with a MnSOD activity close to 1.0 U/mg protein. On either side of this value, the increased sensitivity of S. cerevisiae cells to 14% ethanol might be due to an inability to prevent either superoxide radical- or hydrogen peroxide-induced damages, respectively. These results are supported by the fact that a MnSOD deficiency renders yeast cells more ethanol sensitive.

Drug Resistance, Microbial↗
PubMed1993

Prevalence of diabetic neuropathy with somatic symptoms: a door-to-door survey in two Sicilian municipalities. Sicilian Neuro-Epidemiologic Study (SNES) Group.

In a door-to-door survey conducted in two municipalities of Sicily, we ascertained the prevalence of diabetic neuropathy. Our case-finding was restricted to subjects with somatic symptoms. During phase 1, we administered a screening instrument for peripheral neuropathy to 14,540 persons residing in Santa Teresa di Riva (Messina Province) and Terrasini (Palermo Province). During phase 2, neurologists evaluated those subjects who had screened positive. Diagnoses were based on clinical criteria only, and were reviewed by an adjudication panel. We found 39 persons (27 women, 12 men) affected by diabetic neuropathy. The crude prevalence, as of November 1, 1987, was 268.2 cases per 100,000 population. The prevalence increased with advancing age for both sexes and was consistently higher in women. The most common type was distal symmetric polyneuropathy. The median time between diagnosis of diabetes mellitus and onset of diabetic neuropathy was 8 years, and almost all identified persons with diabetic neuropathy were under treatment for diabetes mellitus.

Adult↗
PubMed1993

The structural organization of layer I of the adult human acoustic cortex. A Golgi and electron microscopy study.

The cellular morphology and the three dimensional cytoarchitecture of layer I of the adult human acoustic cortex were studied by using sagittal, transverse and tangential Golgi preparations and electron microscopy. The prominent neuron of layer I of the acoustic cortex is the Retzius-Cajal cell which is a solitary neuron accompanied by satellite astrocytes located mostly below the pial surface in the upper third of the layer. This neuron demonstrates a marked polymorphism in the various regions of the acoustic cortex. The anterior part of the Hessl convolutions contains Retzius-Cajal cells which are horizontal, multipolar forming dense dendritic arborization by extending long horizontal dendrites to all directions within a tangential plane parallel to the surface of the convolutions. The axon of the Retzius-Cajal cell is a long myelinated nerve fibre which mostly run horizontally, parallel to the pial surface, descending finally to the deeper parts of the layer and projecting a large number of axonic collaterals which radiate in all directions forming dense axonic networks. The Retzius-Cajal cell in the posterior part of the Hessl convolutions is a large polyhedral or triangular cell which extends a large number of dendrites, forming two dendritic networks: one in the upper third of the layer and another in middle part of it. Both of the networks communicate with the axonic collaterals of the Retzius-Cajal cells, forming numerous axodendritic synapses as can be clearly seen in electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intraventricular administration of substance P induces unattached Purkinje cell dendritic spines in rats.

Substance P was infused in the lateral ventricles of twenty Lewis rats for twenty days. The animals under the influence of the substance P demonstrated grooming of the head, the body and the forepaws. On the twentieth day the animals were sacrificed and the cerebellar cortex was processed for electron microscopy. The ultrastructural analysis revealed that although the granule cells, the parallel fibers and the systems of the afferent fibers were intact, numerous unattached Purkinje cell dendritic spines were seen embedded in the soma of the astrocytes, demonstrating postsynaptic differentiation. Numerous unattached spines of the secondary and tertiary dendritic branches of the Purkinje cells were also seen in the molecular layer surrounded by astrocytic sheath. Free unattached spines were also seen not surrounded by any astrocytic process, which did not demonstrate any postsynaptic specialization. The development of unattached Purkinje cell dendritic spines, in an otherwise intact cerebellar cortex, following the intraventricular administration of substance P, suggests that it may act as local growth factor, enforcing the preprogrammed-capability of the Purkinje cells in developing new synaptic surfaces.

Animals↗
PubMed1992

Early ultrastructural changes during thioacetamide-induced apoptosis in rat liver.

An histological and ultrastructural study of the early changes in the liver following a single administration of thioacetamide (TH), was carried out in male Wistar rats. One hour after treatment, apoptosis was already present in the liver. By electron microscopy, the following sequential changes were observed: progressive detachment of hepatocytes from neighboring cells, formation of surface infolds with multiple blebs and, finally, release of several membrane-bounded apoptotic bodies in the extracellular space and into the sinusoidal lumen. Three hours after TH administration, the apoptotic cycle was almost entirely completed, as shown by the presence of phagocytosed apoptotic bodies inside the cytoplasm of intact liver cells. Our study evidences that TH induces apoptosis of liver cell as early as one hour after its administration. Moreover, our data show that the apoptotic cycle may be completed in 3-4 h. From the morphological point of view, apoptosis induced by TH appears indistinguishable from programmed cell death, occurring during embryogenesis or metamorphosis, and from apoptotic cell death seen during regression of mitogen-induced rat liver hyperplasia.

Animals↗
PubMed1992

Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.

Animals↗
PubMed1991

Idiopathic adulthood ductopenia presenting with chronic recurrent cholestasis. A case report.

The paucity of the intrahepatic bile ducts, also known as ductopenia, is a well recognized disorder in pediatric patients. Recently, however, a similar disorder has been reported in adults and termed idiopathic adulthood ductopenia (IAD). We describe a 30-year-old patient with a 15 year history of episodes of jaundice. During icteric episodes, serum levels of bilirubin and alkaline phosphatase were markedly elevated. Between attacks, totalling more than 30, the patient was asymptomatic, but bilirubin and alkaline phosphatase levels were mildly elevated. No neonatal jaundice was present in the patient's history. PBC, PSC and drug-induced cholestasis were excluded. Two needle biopsies of the liver, taken within a 13 year interval, were available. The lobular architecture appeared progressively disturbed by porto-centro-portal bridging septa. In both biopsies, a destructive cholangitis was found. In the last biopsy, the majority of the septal and interlobular ducts appeared severely damaged and, in three out of seven portal tracts, the interlobular bile duct had disappeared. In the parenchyma, the main feature was a severe mainly canalicular bilirubinostasis. The patient described illustrates that IAD may have a clinical picture indistinguishable from benign recurrent intrahepatic cholestasis. The etiology of the disease, in this as in other patients, remains unknown.

Adult↗