PubMed Health⌕ Search

Biomedical subjects

M Curto

Publications and source records attributed to M Curto.

At least 19 recordsLinked to original sources
PubMed2024

Oceanic islands act as drivers for the genetic diversity of marine species: Cardita calyculata (Linnaeus, 1758) in the NE Atlantic as a case-study.

Geographic distribution, as well as evolutionary and biogeographic processes and patterns of marine invertebrate benthic species are strongly shaped by dispersal ability during the life cycle. Remote oceanic islands lie at the brink of complex biotic and abiotic interactions which have significantly influenced the biodiversity patterns we see today. The interaction between geological environmental change and taxon-specific dispersal modes can influence species evolutionary patterns, eventually delimiting species-specific biogeographic regions. In this study, we compare the population genetic patterns of the marine bivalve Cardita calyculata in the northeast Atlantic, discussing the role of Macaronesian islands during past climatic cycles. The genetic structure and diversity patterns were outlined based on SSR-GBAS loci of 165 individuals and on the mitochondrial COI marker of 22 individuals from the Canary Islands, Madeira, Azores and the Mediterranean. The highly structured genetic pattern found among regions and within archipelagos suggests the central role of oceanic islands in promoting the divergence of the species in both the NE Atlantic and the Mediterranean. The high degree of divergence in the COI dataset (> 7%) suggests the existence of potential cryptic speciation that needs to be further explored with a more comprehensive sampling. Such patterns are only congruent with a scenario where C. calyculata populations were maintained during glacial/interglacial cycles, supporting the role of the studied archipelagos as drivers of diversity for marine biota. We stress the importance of developing studies for species with various life history and dispersal modes. In such a way, a more profound understanding of the biogeographic and evolutionary significance of oceanic islands can catalyse directed conservation efforts, especially in the context of the ongoing climate crisis.

Animals↗
PubMed1992

Developmental expression of the S35-S45/SGP-2/TRPM-2 gene in rat testis and epididymis.

Testosterone-repressed prostate message-2 (TRPM-2) was originally isolated and cloned from the regressing ventral prostate of the rat. In this tissue, and in other hormone-dependent tissues such as the mammary gland, this gene is induced in the absence of the appropriate trophic hormone. Sequence analysis of the cDNA and genomic clones of TRPM-2 have demonstrated that the coding sequence of this gene is identical to S35-S45 (also known as SGP-2 and clusterin), which is constitutively expressed by the Sertoli cells of the adult testis. Using Northern, slot blot, S1-nuclease analysis, and in situ hybridization, we have investigated the regulation of TRPM-2 expression in the testis and epididymis during development. Slot blot analysis of RNA extracted from the testis and epididymis of 7-, 14-, 28-, 35-, and 91-day-old rats demonstrates that the gene is induced to detectable levels between days 7 and 14 and that the relative level of expression does not change significantly after day 14. In situ hybridization using frozen sections of testis from day 2-, 7-, 14-, 28-, 35-, and 91-day-old rats confirms that there is little expression of TPRM-2 in the seminiferous epithelium of 7-day-old rats, but this increases considerably after 14 days, primarily in Sertoli cells but also in association with meiotic developing spermatogenic cells. However, TRPM-2 mRNA is expressed in the rete testis at 2 days of age, reaches a peak at 35 days of age, and continues to be expressed in the adult. Slot blot analysis demonstrates that TRPM-2 is also induced in the epididymis between 7 and 14 days of age, although, as has been demonstrated by in situ hybridization, TRPM-2 mRNA is detectable in the epithelial cells in the head of the epididymis but is barely detectable in the midportion or tail regions. Northern analysis suggests that the size of the TRPM-2 transcript in the testis also changes during development. In the early stages of testicular development, the TRPM-2 transcript appears to be a broad band of approximately 1.5 kb, while the transcript in the adult appears to be approximately 1.8 kb in length. S1-nuclease protection assays suggest that this increase in size is not due to differential splicing of the first exon of TRPM-2/SGP-2 and most probably reflects a difference in the polyadenylation of the mRNA in the testis at different times during development.

Animals↗
PubMed1992

The insulin signal and its effects on the pyruvate dehydrogenase complex in circulating lymphocytes of obese children.

1. Studies have shown that in circulating lymphocytes pyruvate dehydrogenase (PDH) is responsive to insulin. 2. To improve existing knowledge on how insulin influences PDH behaviour, situations in which cell responsiveness to insulin is impaired could be of interest. 3. PDH behaviour in circulating lymphocytes from obese children, with high plasma insulin levels and normal glucose tolerance, was examined. 4. Masking and unmasking processes of insulin receptors on the plasma membrane appear to modulate the enzyme response to insulin.

Adolescent↗
PubMed1992

Mitogen-induced liver hyperplasia does not substitute for compensatory regeneration during promotion of chemical hepatocarcinogenesis.

Experiments were designed to determine the efficacy of different types of liver cell proliferative stimuli given during exposure to several liver tumor-promoting regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar rats were initiated with diethylnitrosamine (150 mg/kg body wt). After a 2 week recovery period animals were subjected to promoting regimens, the resistant hepatocyte model, the phenobarbital model and the orotic acid model. While the rats were on these regimens they were given liver cell proliferative stimulus, either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced by the primary mitogen, lead nitrate. Initiated cells so promoted by these regimens were monitored as foci of enzyme-altered hepatocytes positive for gamma-glutamyltransferase and placental glutathione S-transferase or deficient for adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy-induced compensatory regeneration stimulated the promoting ability of the regimens used, direct hyperplasia could not stimulate the formation of foci and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation indicated that there was no significant difference in the extent of DNA synthesis in both the proliferative stimuli irrespective of the promoting procedure used.

2-Acetylaminofluorene↗
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↗
PubMed1991

Acid soluble, short chain esterified and free carnitine in the liver, heart, muscle and brain of pre and post hatched chicks.

1. The behaviour of total acid soluble, short chain esterified and free carnitine in the liver, heart, muscle and brain of chick embryos between 11th and 21st day of development and of 8 and 180-day-old chicks is described. 2. Total acid soluble carnitine fluctuates around the same levels in the brain, liver and muscle until 18th day of development, whereas it attains a peak on that day in the heart. At hatching compared to 18th day, it suddenly increases three times in the muscle, drops not significantly in the heart and brain, but sharply in the liver (-40%). However the levels are always higher than those of the grown chick in the brain but lower in the other tissues. 3. Free carnitine levels are almost constant in all tissues during the embryonic life; if compared to adult ones, they are very much lower in the liver, heart and muscle, but higher in the brain, even in 8 day-old chick. 4. Short chain esterified, carnitine reaches a maximum on 18th day of egg incubation in the liver, brain and heart; in the muscle it stays on constant levels until this day and then rapidly increases so that at hatching it doubles the values. 5. The short chain esterified to free carnitine percentage ratio peaks in all tissues on 18th day of development, attaining figures which are well above those determined in the grown chick.

Animals↗
PubMed1991

Induction of two different modes of cell death, apoptosis and necrosis, in rat liver after a single dose of thioacetamide.

A sequential study of the appearance of liver cell death after thioacetamide (TH) administration was performed in male Wistar rats. Within 3 hours of a single dose of TH, occurrence of cell death by apoptosis was evident around the centrilobular area. Light as well as electron microscopic examination demonstrated the presence of eosinophilic globules, often containing nuclear remnants (apoptotic bodies); they frequently were found within the cytoplasm of intact hepatocytes. The number of apoptotic bodies (ABs) was further enhanced at 6 hours, resulting in a 70-fold increase over the control values. Although necrosis or inflammation could not be observed at this time, as monitored by microscopic analysis as well as by determination of serum glutamate pyruvate transaminase levels, centrilobular necrosis accompanied by massive inflammatory reaction was evident at 12 hours and even more pronounced at 24 to 36 hours. Evidence of liver regeneration was found to occur at 48 hours, and the liver regained its normal architecture between 72 and 96 hours. Studies performed to analyze the activity of 'tissue' transglutaminase (tTG), a presumptive marker of apoptosis, showed that, 1 hour after treatment, TH caused a drastic dose-dependent inhibition of the enzyme activity. This early inhibition was followed by a rapid recovery in tTG activity that paralleled the induction of apoptosis in the liver. Treatment with cycloheximide (CH) 2 hours after TH partially inhibited the incidence of ABs at 6 hours (approximately 30% inhibition). The present study indicates that two different modes of cell death, apoptosis and necrosis, may be induced in a sequential fashion by a single dose of TH.

Alanine Transaminase↗
PubMed1990

Pyruvate dehydrogenase activation by insulin in human circulating lymphocytes and the possible pathway involved.

1. The incubation of human fresh circulating lymphocytes with insulin leads to modifications in the behaviour of the pyruvate dehydrogenase complex (PDH) when the contact medium is supplemented with 50 microM Ca2+ and Mg2+. 2. To investigate the mechanism involved in the PDH responsiveness to insulin in circulating lymphocytes and the role of Ca2+ and Mg2+ in this process, the PDH activity was assayed in lymphocytes combined with insulin and/or a number of substances whose mechanism of action is partially known. 3. Of these some have been seen to mimick insulin effects on PDH, whereas other were tested for the first time in this study.

Enzyme Activation↗
PubMed1990

Cell proliferation and promotion of rat liver carcinogenesis: different effect of hepatic regeneration and mitogen induced hyperplasia on the development of enzyme-altered foci.

A series of experiments was performed to investigate the effect of different types of cell proliferation on the development of enzyme-altered preneoplastic hepatic foci in male Wistar rats. Animals were given a single dose of diethylnitrosamine (100 mg/kg body weight). After a 2-week recovery period liver cell proliferation was repeatedly induced by four or eight necrogenic doses of carbon tetrachloride (compensatory cell proliferation), or by four or eight treatments with three different liver mitogens, namely lead nitrate, ethylene dibromide and nafenopin (direct hyperplasia). The carcinogen altered hepatocytes were monitored as gamma-glutamyltransferase positive or adenosine triphosphatase negative foci. The results indicate that compensatory cell proliferation induced by both four and eight carbon tetrachloride treatments enhanced the growth of diethylnitrosamine-initiated hepatocytes to enzyme-altered foci. On the contrary, repeated waves of cell proliferation induced by liver mitogens did not result in any significant number of enzyme-altered foci.

Adenosine Triphosphatases↗
PubMed1989

The behaviour of pyruvate dehydrogenase in circulating lymphocytes from diabetic children.

The basal and total pyruvate dehydrogenase activities were assayed in circulating lymphocytes from children with juvenile diabetes at diagnosis and after five days of insulin therapy and from control subjects. In untreated diabetic children, basal and total pyruvate dehydrogenase activities were deeply decreased and both showed very similar values; whereas, in control subjects basal activity was about 30% lower than total activity. In diabetic patients treated with insulin (in vivo situation), both basal and total activity levels were equal or even higher than those of the control subjects. The incubation of lymphocytes from diabetic patients with insulin (5 microU/ml) (in vitro situation) stimulates, but less than in vivo, the basal and total pyruvate dehydrogenase activities.

Blood Glucose↗
PubMed1989

Further evidence that mitogen-induced cell proliferation does not support the formation of enzyme-altered islands in rat liver by carcinogens.

Our earlier studies have revealed that direct hyperplasia induced by liver mitogens such as lead nitrate, ethylene dibromide, nafenopin and cyproterone acetate, unlike compensatory cell proliferation induced by partial hepatectomy and CCl4, does not support the formation of enzyme-altered islands induced by chemical carcinogens in the liver. In the previous studies carcinogens were given at the peak of DNA synthesis induced by the liver mitogens. If the mitogens have altered the sensitive phase of the hepatocyte to the carcinogenic attack, administering the carcinogen at one time point following the mitogenic stimulus might have missed the sensitive phase. In order to overcome this possibility in the present study male Wistar rats weighing 200-250 g were given N-methyl-N-nitrosourea (MNU; 60 mg/kg, i.p.) at three points representing G1, S and G2/M phases of the cell cycle following different types of liver cell proliferative stimuli. In another experiment MNU (60 mg/kg, i.p.) and diethylnitrosamine (15 mg/kg, i.p.) were given prior to the administration of proliferative stimuli. The initiated hepatocytes were also assayed following promotion by two different promoting regimens, namely phenobarbital and the resistant-hepatocyte model. Further, the initiated hepatocytes were monitored not only by using the appearance of islands of enzyme-altered hepatocytes but also using the incidence of hepatocellular carcinoma. The results of this study clearly revealed that irrespective of the protocol used, only the compensatory liver cell proliferation but not the mitogen-induced direct hyperplasia supported the formation and the growth of enzyme-altered islands in the liver induced by chemical carcinogens.

Adenosine Triphosphatases↗
PubMed1988

Effects of insulin on pyruvate dehydrogenase in circulating lymphocytes from normal and diabetic rats.

1. The in vivo and in vitro conditions which allow a response of rat circulating lymphocyte PDH to insulin are investigated. 2. In vivo tests show that inactive PDH (PDHi) prevails in diabetic rats and active PDH (PDHa) in hyperinsulinemic rats; in treated with insulin diabetic rats the PDHa/PDHi ratio (1.7) is similar to that of normal rats (PDHa/PDHi ratio = 2). 3. In vitro tests show a responsiveness of PDH to insulin only when 50 microM Ca2+ -Mg2+ and intact lymphocytes are used in the incubation medium. Insulin concentrations and contact time are important variables.

Animals↗
PubMed1988

Insulin modulation of pyruvate dehydrogenase in human circulating lymphocytes.

1. In human circulating lymphocytes pyruvate dehydrogenase (PDH) complex is present in the active (PDHa) and inactive (PDHi) forms. 2. PDHi conversion into PDHa is stimulated when intact lymphocytes are incubated with 5 microU/ml insulin at pH 7.4, for 15 min at 37 degrees C in a medium supplemented with 50 microM Ca2+-Mg2+. 3. The generation of a mediator is strongly suggestive since a cell free preparation from circulating lymphocytes, treated as above described, still stimulates PDHi----PDHa conversion, when combined with either disrupted or intact lymphocytes.

Calcium↗
PubMed1988

Modulation of the activity of hepatic gamma-glutamyl transpeptidase, adenosine triphosphatase, placental glutathione S-transferase and adenylate cyclase by acute administration of lead nitrate.

The effect of a single administration of lead nitrate on the activity of gamma-glutamyltranspeptidase (gamma-GT), adenosine triphosphatase (ATPase), the placental form of glutathione S-transferase (GST-P) and adenylate cyclase (AC), four enzymes widely used as phenotypic markers for preneoplasia, was investigated in the liver of male Wistar rats. The results of the histochemical enzymatic staining indicated that an acute treatment with lead nitrate induces the activity of gamma-GT, mainly in the hepatocytes located around zone I of the liver acinus, with a maximum seen between 72-96 hours. On the other hand, the activity of ATPase was found to be severely inhibited at 2-3 days after treatment, as shown by a strong decrease in the staining of the bile canaliculi of zones II and III. Immunohistochemical analysis revealed that lead nitrate administration also resulted in the appearance in most of the hepatocytes of GST-P, an enzyme whose activity is almost undetectable in normal rat liver, but is elevated in preneoplastic liver lesions. Finally, lead nitrate treatment resulted in an inhibition of AC activity which was maximal after 24 hours.

Adenosine Triphosphatases↗
PubMed1987

Evidence of an insulin generated pyruvate dehydrogenase stimulating factor in rat brain plasma membranes.

1. The results of this study indicates that the binding of insulin to brain plasma membranes activates a membrane protease which, by a trypsin like mechanism, produces a soluble factor that modulates the PDH behaviour when added to brain mitochondria. 2. The supernatant from brain plasma membranes incubated with 0.5 mg/ml trypsin added to mitochondria increases PDH activity levels and cancels PDH inhibition by NaF, as has already been seen when the plasma membranes are incubated with 25 microU/ml insulin. No such effects are obtained when the incubation is run out with 0.5 mg/ml chymotrypsin. 3. The supernatants from insulin or trypsin treated plasma membranes retain their activating properties on mitochondrial PDH also after dansylation; from these preparations a dansylated active on PDH material was separated by monodimensional chromatography on HPTLC silica Gel plates, using chloroform/1-butanol (93:7 v/v) as a solvent. 4. Insulin incubation of plasma membranes pretreated with protease inhibitors (leupeptin, phenylmethylsulfonylfluoride) or with exogenous trypsin, but not chymotrypsin substrates (esters of arginine and tyrosine) yields an inactive supernatant on PDH. 5. Insulin treated plasma membrane supernatants lose all stimulating properties on PDH after incubation for 1 hr with 2 mg/ml trypsin or chymotrypsin.

Animals↗
PubMed1987

Cell proliferation in rat kidney induced by 1,2-dibromoethane.

The effect of a single intragastric injection of 1,2-dibromoethane was investigated in kidneys of male Wistar rats. DNA synthesis as measured by the incorporation of tritiated thymidine was found to be approximately 5 times greater than that of controls 20-30 h after treatment. DNA synthesis was followed by a striking increase in the mitotic activity with a maximum at 30 h. The labeling and mitotic activities, after an initial increase, fell rapidly 48 h after treatment even though they were still higher than those of control animals. 1,2-Dibromoethane-induced cell proliferation is not a regenerative response because at the dose used in this study, no tubular necrosis was observed by histologic examination.

Animals↗
PubMed1986

Effect of insulin on pyruvate dehydrogenase in a mixture of plasma membranes and mitochondria from normal and alloxan treated rat brains.

In a mixture of plasma membranes/mitochondria from normal rat brain, pyruvate dehydrogenase (PDH) is present in the active (PDHa) and the inactive (PDHi) form; the latter is converted into the former by preincubation with Ca2+ and Mg2+ and represents about 40% of total PDH (PDHt = PDHa + PDHi). Incubation with increasing insulin concentrations activates PDHa and PDHt, the maximum being reached at 25 microU/ml insulin; inhibition appears with further insulin increase. In a mixture of plasma membranes and mitochondria from alloxan rat brain PDHa activity markedly decreases; no activation is achieved by preincubation with Ca2+ and Mg2+. However an activating effect of Ca2+ and Mg2+ appears when the mixture is added and incubated with increasing insulin concentrations. PDHa and PDHt activity reaches a maximum of stimulation at 25 microU/ml insulin; the activation is reduced at higher concentrations of insulin though no inhibition appears. ATP partially inhibits PDHa in normal and alloxan rat brain plasma membrane/mitochondria mixtures; this effect is completely cancelled by 25 microU/ml insulin.

Animals↗