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Biomedical subjects

F Serra

Publications and source records attributed to F Serra.

At least 19 recordsLinked to original sources

Microstructural analysis of the effects of incorporation of myelin basic protein in phospholipid layers.

We report an X-ray reflectivity study on the effects of adsorption of myelin basic protein (MBP) on Langmuir monolayers and on deposited Langmuir-Schaefer multilayers of the phospholipid dipalmitoyl phosphatidylglycerol (DPPG). We provide for the first time, direct microscopic evidence on the destructuring effects of MBP leading to plasticity of the DPPG layers supporting commonly accepted models of the stabilizing role of MBP in the myelin membrane. We also show how protein adsorption onto the layer is determined both by electrostatic and nonspecific hydrophobic interactions.

Adsorption↗

13C and 18O isotopic analysis to determine the origin of L-tartaric acid.

Due to the ever-increasing amount of attention paid to the 'naturalness' of ingredients in food and beverages by both consumers and controlling authorities, the search for suitable methods for the characterisation of origin is of primary importance. Within the European Community the wine production industry is often faced with the problem of origin control of tartaric acid. This has led to the decision that only L-tartaric acid extracted from grapes (therefore natural) should be used. In order to implement these regulations, a screening of different techniques has been carried out to assess the methodology that best identifies the origin of the tartaric acid. It has already been indicated in previous scientific literature that isotope ratio mass spectrometry is an ideal technique for this type of identification. In this paper we present the results obtained for the measurement of the isotope ratios of carbon-13 and oxygen-18 of natural and synthetic samples of L-tartaric acid considering also natural samples of different geographical origin and years of production.

Carbon Isotopes↗

[Microsurgery of canalicular stenosis].

The microsurgical treatment of canalicular stenosis is indicated in localized stenosis. The goal is to restore lacrymal mucosa continuity in order to re-establish spontaneous lacrymal drainage. Stenosis located close to the puncti can be reached by the direct approach, those close to the lacrymal sac require an approach via the common canaliculus. The surgical indications and techniques are developed, with particular attention given to common canaliculus repair and the new surgical approach to reach it.

Dacryocystorhinostomy↗

[Upper cosmetic blepharoplasty and the eye brow].

Upper cosmetic blepharoplasty allows to treat cutaneo-orbicularis excess of the upper eyelid, which is often associated with fat prolapse. Using the same surgical way, it is also possible to treat external heaviness of the brow, mild brow ptosis and glabellar wrinkles. We will describe the most important stages of these different surgical techniques.

Blepharoplasty↗

General aspects on the assessment of functional foods in the European Union.

During the last 6 y, the European Union has undergone a profound qualitative change in the focus on food safety problems. In 1997, nine new scientific committees were created, including the Scientific Committee on Food (SCF) and the Scientific Steering Committee (SSC), and were put under the auspices of the Directorate General in charge of defending consumer interests and health. The process is foreseen to be completed by the incorporation in 2003 of all food safety activities of these committees into the European Food Safety Authority (EFSA). Among the immediate challenges in the near future are the scientific and technological developments and the regulatory measures for the so-called 'functional foods', which can positively affect the health and well-being of consumers. Functional foods are a recent phenomenon in Europe and are, as yet, not covered by any specific legislation. The two key aspects in the evaluation of functional foods are safety and efficacy. Whereas safety can be covered under different legislative umbrellas such as novel foods (NFs), foods for particular nutritional purposes, supplements, additives and others, the issue of evaluation of their efficacy is only at a very early stage since the criteria to establish the validity of 'health claims' has not been clearly addressed at a European level.

European Union↗

Differentiation of the geographical origin of durum wheat semolina samples on the basis of isotopic composition.

The identification of the geographical origin of foods is attracting great interest from consumers and producers since it may be used as a criterion for guaranteeing quality and authenticity. Stable isotope techniques can provide useful information on the origin of food products. The natural abundance isotopic ratios of carbon, oxygen and nitrogen were determined and a comparison made between the isotopic content of samples originating from Italy and those of samples originating from other countries (Canada, Turkey, Australia). A correlation was found between the isotopic composition and geographical origin of the samples. The relationship between isotopic content and the latitude has been confirmed.

Australia↗

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

Androstanes↗

Obesity: molecular bases of a multifactorial problem.

Obesity could well become the most common health problem of the 21st century. There are more opportunities to consume large quantities of food: big portions of tasty, varied food, at reasonable prices, are available everywhere. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, since for thousands of years our species evolved in circumstances where nutrients were in short supply. The response of each individual to diet and other environmental factors varies considerably, depending on the characteristics of his/her body weight control mechanisms. The differentiating element in the future, especially as regards the dietary and pharmacological control of obesity, will be knowledge of an individual's possible response depending on his/her genetic background. Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a)feeding control, which determines the sensations of satiety and hunger through processes that depend on an interplay between internal signals (notably leptin) and environmental factors; b) energy efficiency, in particular the activation of thermogenesis mediated by uncoupling proteins (UCPs) that makes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by which cells specialised in fat storage (adipocytes) are formed, which is controlled by an interplay of transcription factors, including members of the C/EBP, PPARgamma and ADD families. The knowledge of a growing number of genes and molecules implicated in these three types of processes and of their metabolic relationships is leading toward a molecular understanding of the body weight regulatory system, and is paving the way for new methods of obesity control, especially pharmacological but also nutritional and possibly involving genetic intervention.

Adipose Tissue↗

Turbidite Megabeds in an Oceanic Rift Valley Recording Jökulhlaups of Late Pleistocene Glacial Lakes of the Western United States.

Escanaba Trough is the southernmost segment of the Gorda Ridge and is filled by sandy turbidites locally exceeding 500 m in thickness. New results from Ocean Drilling Program (ODP) Sites 1037 and 1038 that include accelerator mass spectrometry (AMS) 14C dates and revised petrographic evaluation of the sediment provenance, combined with high-resolution seismic-reflection profiles, provide a lithostratigraphic framework for the turbidite deposits. Three fining-upward units of sandy turbidites from the upper 365 m at ODP Site 1037 can be correlated with sediment recovered at ODP Site 1038 and Deep Sea Drilling Program (DSDP) Site 35. Six AMS 14C ages in the upper 317 m of the sequence at Site 1037 indicate that average deposition rates exceeded 10 m/k.yr. between 32 and 11 ka, with nearly instantaneous deposition of one approximately 60-m interval of sand. Petrography of the sand beds is consistent with a Columbia River source for the entire sedimentary sequence in Escanaba Trough. High-resolution acoustic stratigraphy shows that the turbidites in the upper 60 m at Site 1037 provide a characteristic sequence of key reflectors that occurs across the floor of the entire Escanaba Trough. Recent mapping of turbidite systems in the northeast Pacific Ocean suggests that the turbidity currents reached the Escanaba Trough along an 1100-km-long pathway from the Columbia River to the west flank of the Gorda Ridge. The age of the upper fining-upward unit of sandy turbidites appears to correspond to the latest Wisconsinan outburst of glacial Lake Missoula. Many of the outbursts, or jökulhlaups, from the glacial lakes probably continued flowing as hyperpycnally generated turbidity currents on entering the sea at the mouth of the Columbia River.

Journal Article↗

Stimulation of uncoupling protein 1 expression in brown adipocytes by naturally occurring carotenoids.

OBJECTIVE: To assess the effect of naturally occurring carotenoids on brown adipocyte proliferation and differentiation. The rationale behind is that certain carotenoids have provitamin A activity in mammals, and that one of the active forms of vitamin A, (retinoic acid) is known to behave as a transcriptional activator of the key gene for brown fat thermogenesis, the one encoding the uncoupling protein thermogenin (UCP1). DESIGN: Confluent primary cultures of mice brown adipocytes were treated with various concentrations of carotenoids. Cell morphology, total culture protein content, the DNA synthesis rate, and the levels of UCP1, retinoic acid receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha) were analysed. RESULTS: Treatment with beta-carotene, alpha-carotene and lutein promoted UCP1 expression in a dose-dependent manner, with an effectiveness that was related to their potency as vitamin A precursors. Cell morphology, total culture protein content at confluence and DNA synthesis rate were unaffected after carotenoid treatment up to 10 microM. CONCLUSION: The results indicate that carotenoids can positively affect the expression of UCP1 without altering brown adipocyte proliferation.

Adipocytes↗

[Intestinal infarct caused by giant cell arteritis].

Arteritis of giant cells compromising extracranial and particularly intestinal tissues is not frequent. Therefore, it is common practice to make the diagnosis retrospectively after analyzing the surgical sample. A case is presented of an 83 year old woman admitted to the Clinical Department with a clinical course of 3 days of evolution characterized by fever and pain in the left hemiabdomen. Her personal medical history included multiple diverticulosis of colon, collecistectomy and appendicectomy. Laboratory tests showed that uremia was 0.75 g/L (N.L to 0.45 g/L), V.E.S. 90 mm at the first hour, and the rest of the determinations were normal. The chest and abdomen rays as well as the abdomen and pelvis ecographies were normal. A diagnosis was reached as acute diverticulitis and the patient was treated with 400 mgr of ciprofloxacina and 2,000 mgr a day of metronidazol. She continued in a feverish state and with abdominal pain, so that an anexial tomography of abdomen was taken. It showed a widening of peritoneal fascias with scarce liquid in the left parietocolic dripping and Douglas septum. After 96 hours, surgery exploration was done and injuries in the left colon revealed compatibility with an infarct of the colon which had to be extirpated. Pathological examination revealed an infarct of colon due to a secondary arterial thrombosis characteristic of giant cell arteritis. After the diagnosis, immunological studies and biopsy of the left temporal artery were performed and reported as normal. The patient was treated with 40 mgr of prednisone a day improving rapidly.

Aged↗

Scintigraphic assessment of swallowing after horizontal supraglottic laryngectomy.

OBJECTIVE: Oral-pharyngo-esophageal scintigraphy (OPES) proved to be able to demonstrate the pharyngeal residue of the radioactive bolus after deglutition and the presence and amount of tracheobronchial aspiration, and to calculate exactly the transit time of the various swallowing phases. The aim of this study was to evaluate the real objective effectiveness of OPES in order to assess the degree of swallowing recovery after horizontal supraglottic laryngectomy (HSL). METHODS: Nineteen patients entered the study, and 17 healthy subjects were included as control group (group 1). Nineteen patients in whom HSL had been performed at least 1 year before underwent OPES. They were divided into two groups: 13 patients (group 2) in whom the tracheal cannula had been removed and swallowing, phonatory, and respiratory functions were satisfactory and 6 patients (group 3) in whom the tracheostomy tube was still in situ for aspiration of liquids and scarring of the laryngeal vestibule. RESULTS: Our results showed that in the patients who underwent HSL, all scintigraphic semiquantitative parameters and particularly aspiration percentage values and Pharyngeal Ritention Index (PRI) at 10 and 60 seconds were able to pinpoint some residual "subclinical" alteration and/or minimal surgical sequelae frequently observed after this kind of functional surgery, even though a substantially satisfactory recovery was achieved clinically (group 2 versus group 1). In addition, aspiration amounts in group 3 were markedly higher than those in group 2 (p < .0002), and mean PRI values at 10 and 60 seconds were significantly different (p < .0001) from normal mean control values (group 1). CONCLUSION: Oral-pharyngo-esophageal scintigraphy may be regarded as a noninvasive, well-tolerated technique, with a radiation body burden within satisfactory limits of radioprotection. It appeared to be also sensitive in assessing the swallowing recovery after HSL.

Adult↗

Bilateral congenital pseudarthrosis of the clavicle report of a case with clinical, radiological and neurophysiological evaluation.

Congenital pseudarthrosis of the clavicle is a rare condition. Bilateral involvement is extremely rare: only seven cases have been reported in the literature. Although the anatomy of the thoracic outlet can be markedly altered by the hypermobility of the shoulder and although few cases with mild symptoms suggesting brachial plexus impairment have been reported, the neurological status of the brachial plexus in congenital pseudarthrosis of the clavicle has not been well assessed. We report a case of bilateral congenital pseudarthrosis of the clavicle in which clinical, neurophysiological and radiological evaluations were performed.

Child, Preschool↗

Involvement of the retinoblastoma protein in brown and white adipocyte cell differentiation: functional and physical association with the adipogenic transcription factor C/EBPalpha.

We investigated the expression of the retinoblastoma protein (pRB) in adipocytes and its possible interaction with the adipogenic transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) in controlling the acquisition of the terminally differentiated adipocyte phenotype. The pRB was expressed (as measured by immunoblotting and/or immunofluorescence) in mice brown and white adipose tissue and in cultured adipocytes that showed lipid accumulation and expressed specific differentiation markers such as aP2 (measured using a specific cDNA probe) and in the case of brown adipocytes UCP-1 (measured using specific antibodies), but was undetectable in proliferative undifferentiated preadipocytes. Transient transfection experiments revealed a functional interaction between pRB and C/EBPalpha affecting transcription from the ucp-1 gene promoter. Thus, in immortalized brown adipocytes, co-transfection of both a C/EBPalpha and a pRB expression vectors maximally enhanced the expression of reporter chloramphenicol acetyltransferase driven by the ucp-1 promoter. Interestingly, C/EBPalpha inhibited reporter gene expression in CHO cells in an effect that was also potentiated in the presence of pRB. A positive effect of pRB on transcription from the ucp-1 promoter could be detected in C/EBPalpha-/-fibroblasts only after forced to overexpress C/EBPalpha, suggesting that the effect of pRB is dependent on its interaction with C/EBPalpha. We also found evidence that pRB and C/EBPalpha can directly bind to each other in vitro. Our results show that the expression of pRB is restricted to differentiated adipocytes, and provide evidence of a physical and functional interaction between pRB and C/EBPalpha that affects the transcriptional activity of the later on a brown adipocyte-specific gene.

3T3 Cells↗

Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats.

OBJECTIVE: To investigate the effects of overfeeding on a high fat diet, enriched in coconut oil, and the influence of food restriction on the uncoupling protein (UCP1) expression and on body fat content. DESIGN AND SUBJECTS: In experiment I, female Wistar rats were fed ad libitum either a normal-fat diet (control group, C) or a high-fat diet (HF), enriched in coconut oil, for 7 weeks. In experiment II, HF rats after finishing experiment I were fed (for 3 weeks) either the normal-fat diet (group CAHF, Control After High Fat) or food restricted diets which provided 60% of the energy intake of group CAHF: a group fed a low-energy, normal-fat diet (LENF) and another fed a low-energy, high-fat diet (LEHF). MEASUREMENTS: Body and fatty depot weights. Food intake. Protein and UCP1 levels of interscapular brown adipose tissue. RESULTS: High-fat diet feeding promoted an increase in body fat content, body weight and UCP1 levels. Energy restriction induced similar body weight reduction in groups LENF and LEHF. However, some adipose depots were more strongly reduced in the rats fed the high-fat diet enriched in coconut oil (group LEHF) than in the rats fed the normal-fat diet (Group LENF). Specific UCP1 was 2.0 (group LENF) and 3.4 (group LEHF) times higher than in controls (group CAHF). CONCLUSION: The coconut-oil enriched diet is effective in stimulating UCP1 expression during ad libitum feeding and in preventing its down regulation during food restriction, and this goes hand in hand with a decrease of the white fat stores.

Adipose Tissue↗

Synthesis, cardiotonic activity, and structure-activity relationships of 17 beta-guanylhydrazone derivatives of 5 beta-androstane-3 beta, 14 beta-diol acting on the Na+,K(+)-ATPase receptor.

A series of digitalis-like compounds, with the lactone ring shifted from the original position through a spacer or replaced by a series of guanylhydrazone substituent-bearing chains, was synthesized and evaluated for inhibition of Na+,K(+)-ATPase and for inotropic activity. The highest Na+,K(+)-ATPase inhibition (IC50) and inotropic activity (EC50) were reached with the vinylogous guanylhydrazone 5 where a cardenolide-like polarized alpha,beta-unsaturated system and a basic guanidino group were both present at the 17 beta-position; for this compound IC50 and EC50 values were comparable to or higher than those of Thomas' parent guanylhydrazone 1, digitoxigenin, and digoxin. A substantial improvement of the desired positive inotropic activity versus the toxic arrhythmogenic concentration was not reached within this series; only a slightly better therapeutic index can be envisaged for compounds 5 and 4, even though, for the latter, to the detriment of potency, presumably because of a weaker interaction with the receptor, due to the lack of a cardenolide-like polarized system.

Androstanes↗

Differential sensitivity of leukemic and normal hematopoietic progenitors to the killing effect of hyperthermia and quercetin used in combination: role of heat-shock protein-70.

Autologous bone-marrow transplantation (ABMT) is widely used in the treatment of acute leukemias where a matched sibling donor is not available for allogeneic transplantation. However, a major problem in ABMT is relapse, and ex vivo purging may be very important in preventing it. We show here that quercetin enhances the growth-inhibitory effect of hyperthermia (HT) in AML (19 cases) and ALL (6 cases) leukemic blasts. Furthermore, the inhibitory effect of this combined treatment resulted in leukemic-cell apoptosis. On the contrary, normal hematopoietic progenitors were neither growth-inhibited nor induced to apoptosis by HT-plus-quercetin treatment. To explain this difference in sensitivity of leukemic and normal hematopoietic progenitors, we analyzed the effect of quercetin on heat-induced expression of heat-shock protein-70 (HSP-70), which has been shown to be important in regulating thermosensitivity. We found that quercetin inhibits heat-induced HSP-70 expression both at protein and at mRNA levels in AML and ALL blasts. In normal CD34+ progenitors, the combined treatment with HT and quercetin did not reduce HSP-70 expression and did not induce cell apoptosis. Considering the difference in heat sensitivity of normal CD34+ and leukemic progenitors in the presence of quercetin, the combined use of HT and quercetin could constitute a purging protocol for ABMT.

Adult↗

Retinoic acid modulates retinoid X receptor alpha and retinoic acid receptor alpha levels of cultured brown adipocytes.

A novel potential regulatory pathway of brown adipose tissue (BAT) thermogenesis was recently recognized after identifying retinoic acid (RA) as a transcriptional activator of the uncoupling protein (UCP) gene. Here we provide evidence that the UCP responsiveness to RA in primary cultures of brown adipocytes involves RA receptor alpha (RAR alpha), and show, in the same system and also in CHO cells, that RA down-regulates the steady-state levels of RAR alpha and especially of retinoid X receptor alpha, suggesting autoregulation of the retinoid pathway and therefore supporting the idea of a physiological role for it in controlling the thermogenic capacity of BAT.

Adipocytes↗