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Biomedical subjects

F Serra

Publications and source records attributed to F Serra.

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

Inhibition of replication of HIV in primary monocyte/macrophages by different antiviral drugs and comparative efficacy in lymphocytes.

Several anti-HIV drugs acting on different steps of virus replication were tested in our experimental model of primary monocyte/macrophages; the results were compared with the activity found in lymphocytes. Nucleoside analogues (AZT, ddI, ddC, d4T, PMEA, 3TC etc.) show greater activity in macrophages (M/M) than in lymphocytes. In particular, the EC50 of AZT, ddC, and ddI in M/M is 2- to 100-fold lower than that found in lymphocytes. This greater efficacy of nucleoside analogues in M/M depends on the enhancement of their chain-terminating activity by the low levels of endogenous deoxynucleoside-triphosphates (dNTP) usually found in resting cells such as M/M. Non-nucleoside reverse transcriptase inhibitors (NNRTI) do not act as chain terminators (thus their antiviral effect is not related to the intracellular concentrations of dNTP); as a consequence the activity of TSAO, HEPT, TIBO, and other NNRTI tested in M/M is similar to that found in lymphocytes. Regarding inhibitors of binding and fusion of HIV, we found that their anti-HIV activity is markedly decreased (or even nullified) when M/M are treated with cytokine activators of M/M function and enhancers of HIV replication. More relevant from a clinical standpoint, protease inhibitors are able to inhibit HIV replication in chronically infected macrophages (i.e., cells carrying the proviral genome already integrated in the host genome). All other inhibitors of late stage of virus life cycle tested (antisense-rev, anti-tat, interferon-alpha and -gamma, phosphorothioate analogues, GLQ-223, etc.) were totally inactive in chronically infected macrophages. The different effects of various classes of HIV inhibitors in lymphocytes and macrophages suggests that AIDS therapy should consider all aspects of the pathogenesis of HIV infection and must be restricted to drugs, or combinations of drugs, active against both lymphocytes and M/M in all body compartments where the virus hides and replicates.

Anti-HIV Agents↗
PubMed1997

The growth of primary low-grade B-cell gastric lymphoma is sustained by Helicobacter pylori.

BACKGROUND: The growth of primary low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma is an antigen-dependent process CASE: We were able to document the influence of Helicobacter pylori on the natural history of primary low-grade B-cell gastric MALT lymphoma in a case investigated by means of polymerase chain reaction for IgH rearrangement. In this case the presence or absence of the bacterium appeared to affect both clinical manifestations and histologic features of the neoplasia, with an acceleration or a slowing down of the neoplastic expansion, respectively. CONCLUSIONS: We identified H. pylori as an antigenic stimulus that supports the growth of MALT-type lymphoma. This finding enables us to make some considerations about the management of the disease.

Aged↗
PubMed1996

Essential cis-acting elements in rat uncoupling protein gene are in an enhancer containing a complex retinoic acid response domain.

Transgenic mice were generated with a transgene containing the 211-base pair (bp) enhancer and 0.4 kilobase pairs of 5'-flanking DNA of the uncoupling protein (ucp) gene. Expression of this transgene was restricted to brown adipose tissue and was inducible by cold exposure or treatment of transgenic mice by norepinephrine, retinoic acid (RA), or CL-316,243 beta3-adrenoreceptor agonist. A search for retinoic acid response elements in the ucp gene enhancer was undertaken using mutagenesis and transfection of cultured cells with chloramphenicol acetyltransferase constructs. Deletion or mutations of several putative retinoic acid response elements were ineffective. Mutations of a TGAATCA region dramatically decreased the transcriptional activity in the presence of RA. In vitro this region was able to bind a complex containing proteins recognized by antibodies against Jun or Fos. Mutations of an adjacent region related to an inverted repeat of type 2 also markedly decreased RA effect. This region was able to bind in vitro retinoid X receptor alpha and retinoic acid receptor beta. The two regions form an activating region between bp -2421 and -2402 (referred to as the ucp gene-activating region), which has an enhancer activity but cannot confer RA response to a promoter. This response was obtained with a larger DNA fragment (bp -2489 to -2398) constituting a complex RA response domain.

Adipose Tissue, Brown↗
PubMed1996

137Cs content in the fruit bodies of various Tuber species.

In this research, the concentration of 137Cs in the fruit bodies of the Tuber species T. magnatum Pico, T. borchii Vitt., T. aestivum Vitt., and T. excavatum Vitt. collected in three different regions of Italy was determined. The values obtained have been compared to the soil concentration of 137Cs, and the transfer factor was determined. The radiocesium content of the examined fruit bodies ranged from 2.5 Bq kg(-1) to 33.3 Bq kg(-1) fresh weight; the median transfer factor values of the four species ranged between 0.06 and 0.6. Our findings indicate that the radiocesium level in truffles from these regions of Italy is generally low, and, thus, their consumption is not of radiological concern. The results may suggest certain hypotheses as to the mechanisms involved in radiocesium uptake in these fungi.

Ascomycota↗
PubMed1995

Selective loss of the uncoupling protein from light versus heavy mitochondria of brown adipocytes after a decrease in noradrenergic stimulation in vivo and in vitro.

The relative stability against a decrease in adrenergic stimulation of the uncoupling protein (UCP) incorporated into different mitochondrial fractions was investigated in brown-fat-cell cultures. Cultures were initiated with undifferentiated cells from young mice and were acutely stimulated with noradrenaline at confluence (day 7). Cells were harvested just after the finish of the 24 h stimulation treatment or 24 h later, and three mitochondrial fractions were isolated by differential centrifugation: the M1 fraction (1000 g), the M3 fraction (3000 g) and the M15 fraction (15,000 g). The results obtained in vitro indicate that removal of adrenergic stimulation determines a selective loss of UCP from the lightest mitochondrial fractions (M3 and M15). Similar results were obtained in a situation in vivo (24 h starvation in mice) which is known to lead to a decreased noradrenaline input to brown adipose tissue, with decreased UCP levels. Thus brown adipocytes possess different mitochondrial subpopulations, which exhibit characteristic changes in their UCP turnover in response to thermogenic signals.

Adipose Tissue, Brown↗
PubMed1994

Cerebro-facio-articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome.

Van Maldergem et al. (1992) described a new syndrome in an 11-year-old girl, characterized by: mental retardation, hypotonia, dysmorphic facies with telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth, malformed ears, finger camptodactyly, and joint hyperlaxity. In this report we present a 5-year-old girl with very similar clinical findings. We confirm the existence of this condition as an independent clinical entity, and we propose that, based on the major clinical manifestations, it should be defined as "cerebro-facio-articular" syndrome.

Abnormalities, Multiple↗
PubMed1994

Brown and white adipose tissue adaptive enzymatic changes on amino acid metabolism in persistent dietary-obese rats.

The objective was to determine the effects of persistent obesity on amino acid enzymes in white (WAT) and brown (BAT) adipose tissues. Dietary obesity was induced by feeding a cafeteria diet ad libitum for 3 months, then it was removed and the obese animals received the same diet as controls for 5 months. Dietary-induced obesity was persistent as obese rats showed a stable, higher body weight than controls (26%). Key enzymes of alpha-amino nitrogen metabolism were studied and results showed reduced activities in obese rats: glutamine synthetase (45%), AMP deaminase (52%), alanine aminotransferase (66%) and glutamate dehydrogenase (68%) in BAT, whereas WAT of obese animals only showed lower aspartate aminotransferase activity (47%) with respect to the controls. We can conclude that these adaptations in amino acid metabolism were exclusively dependent on the obese status as they were observed in an obesity model in which obese rats eat the same diet as controls.

AMP Deaminase↗
PubMed1993

Moderate maternal drinking and outcome of pregnancy.

The adverse effect of light or moderate maternal drinking during pregnancy on the well being of the newborn has been investigated. The study group included 2145 live births in the obstetric units of 11 Italian cities between February 1989 and July 1990. A detailed life style questionnaire was administered to the mothers. Information on the newborn was collected from clinical records as well as from a clinical examination. Both univariate and multivariate analyses were suggestive of a decrease in mean birth weight associated with maternal drinking pregnancy, especially in women who also smoked during pregnancy. This effect was higher in male newborns. The occurrence of low birth weight (< 2500 g.) was more frequent in women drinking during pregnancy in both smokers and non-smokers (for this latter group an effect is suggested only for a daily consumption of more than 10 grams of absolute alcohol). Maternal alcohol drinking of more than 20 grams of absolute alcohol per day also increased the risk of preterm delivery (OR = 2.35; 95% CI: .98-5.59). Finally, an increase in the rate of early jaundice was found, also associated with maternal drinking (OR = 3.30; 95% CI: 1.03-10.54).

Adult↗
PubMed1993

Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats.

Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity.

Amino Acids↗
PubMed1992

Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT.

Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5-40 micrograms), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20 micrograms) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12-60 micrograms) significantly increased resting oxygen consumption (VO2 by approximately 15-20%) in conscious rats, without apparent effects on physical activity. Small increases (5-7%) in VO2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injections of tyrosine or leucine (15-18 micrograms) significantly increased VO2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF). In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist alpha-helical CRF9-41 (25 micrograms, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methysergide (20 micrograms, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1991

Altered blood amino acid distribution in genetically obese mice.

The present study was undertaken to determine whether the alteration in amino acid distribution between the plasma and cellular compartment of the blood, previously described in dietary-obese rats, also occurs in genetically obese mice. The blood concentration of individual amino acids and its distribution between plasma and cells of lean and genetically obese mice (ob/ob) have been measured. The results demonstrated that genetically obese mice showed a decrease (55%, P = 0.0489) of free amino acids in the blood cells. Most amino acids were affected and among the most noteworthy characteristics was the observation that the reduction in concentration was more pronounced for the total concentration of the essential amino acids which was reduced by 76% (P = 0.0112) compared to cells of lean mice. These results suggest that an altered amino acid distribution between plasma and blood cells is a consequence of both diet-induced and genetic obesities.

Amino Acids↗
PubMed1991

Calpastatin level in spontaneously hypertensive rats.

We studied calpastatin activity in erythrocytes of Milan hypertensive and prehypertensive rats, in their normotensive controls, in F1 and F2 hybrids, and in two inbred strains derived from F2, one hypertensive and the other normotensive. Our results show that the decrease in calpastatin activity observed in Milan hypertensive rats was not caused by hypertension, it was transmitted in a recessive way in heterozygous, and it was not correlated to hypertension.

Animals↗
PubMed1991

Generalized osteoporosis in non-steroid treated rheumatoid arthritis.

To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were detected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P less than 0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P less than 0.001) and years postmenopausal (P less than 0.01), but not with duration of disease. By multiple linear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone loss in rheumatoid arthritis.

Absorptiometry, Photon↗
PubMed1991

Dietary obesity shows adaptations of amino-acid metabolism on enzyme activities to save amino nitrogen.

An increased aspartate transaminase in the liver of dietary (post-cafeteria) obese rats was found. It was consistent with the functionality of the malate-aspartate shuttle, that could be responsible for enhancement of metabolic efficiency. The muscle and intestine of obese rats showed a greater capacity for alanine and glutamine synthesis than the controls. Furthermore, enterocyte adaptations in the obese rats indicated higher capabilities for the intake of nitrogen than in the controls. In conclusion, the pattern of amino-acid enzyme activities reflected adaptations to keep from amino nitrogen depletion in dietary obesity which were compatible with an enhancement of the metabolic efficiency.

AMP Deaminase↗
PubMed1991

Dietary-induced permanent changes in brown and white adipose tissue composition in rats.

We have previously observed that feeding rats a cafeteria diet causes excess weight gain and changes in tissue composition. The object of this study was to assess whether these alterations were sustained after withdrawal of the palatable diet in the rat. The results showed that the obesity was not reversed by feeding a standard diet ad libitum for five months after withdrawal of the cafeteria diet. Body weight was 26 per cent greater than in control rats and tissue composition showed permanent alterations. The excess weight of lumbar white adipose tissue was due mainly to lipid content (86 per cent) and this was also true, but to a less extent, for interscapular brown fat (59 per cent). Increased brown fat mass was a result of hyperplasia and hypertrophy, whereas increased lumbar white fat was mainly a result of hyperplasia alone. In conclusion, changes in tissue composition, particularly in fat depots, were permanent and could be ascribed to the obesity per se, and not to the diet composition.

Adipose Tissue↗