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Biomedical subjects

A Giuffrida

Publications and source records attributed to A Giuffrida.

At least 19 recordsLinked to original sources
PubMed2005

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells.

Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.

Apoptosis↗
PubMed2005

[Hyperhomocysteinemia: associated obstetric diabetes and fetal malformations].

In its biological complexity, pregnancy represents a challenge both for the maternal organism and the fetal development and growth. During this period, some peculiar pathologies of pregnancy can occur which can involve or the fetus only i.e.: spontaneous pregnancy loss, intrauterine growth retardation, defects of neural tube, until the intrauterine fetal death; or pathologies occurring in the placenta and thus involving maternal organism and fetus too, such as pre-eclampsia. All these pathologies recognize many risk factors, among them the hyperhomocysteinemia. Hyperhomocysteinoemia can be caused by enzymatic defects or lack of some vitamins cofactors (vitamin B6, vitamin B12 and folic acid). The genetic defects which, as homozygous genotype, cause high plasma levels of homocysteine are already well known; they lead to an activity reduction of the enzymes responsible for their metabolism, for example: the deficiency of cystathionine beta-synthase; the deficiency of the methylcobalamine production; the deficit of the 5-10 methylenetethrahydrofolate reductase (MTHFR). However, even the heterozygous genotypes, which have a variable incidence from 1/70 to 1/200 and directly of 5-15% for the C677T mutation of the 5-10 MTHFR, can determine a mild hyperhomocysteinemia with a consequent cardiovascular risk. The close implications, widely demonstrated in the international literature, between hyperhomocysteinemia and the maternal-fetal diseases are described.

Atherosclerosis↗
PubMed2003

Exercise activates the endocannabinoid system.

Extensive documentation exists showing that exercise induces analgesia and sedation. Despite decades of research attempting to explicate a neurochemical basis for these phenomena, the mechanism underlying these changes is unknown. Using trained male college students running on a treadmill or cycling on a stationary bike for 50 min at 70-80% of maximum heart rate, we report here the first evidence that exercise of moderate intensity activates the endocannabinoid system, suggesting a new mechanism for exercise-induced analgesia and possibly other physiological and psychological adaptations to exercise.

Adolescent↗
PubMed2003

Application of risk management to the production chain of intensively reared fish.

Principles of risk management, as a part of risk analysis, are described with respect to their application to the production chain of intensively reared fish. According to the outcomes of the FAO/WHO Expert consultation on the Application of Risk Management (Rome, 1997), there are four steps: risk evaluation, risk management option assessment, implementation of management decisions, and monitoring and review. There is a lack of information on risk assessment for farmed fish though, regarding bacteriological hazards, the data on farmed fish pathology and microbiology suggest a potential prevalence of Vibrio spp. and Aeromonas spp. Other bacterial contaminants could be introduced on handling during selection and packaging of products. On the basis of the above qualitative risk evaluation, risk management options have been individuated. These concern the monitoring of the health status of fish during the fattening period, harvest parameters, hygiene of selection and packaging, and storage characteristics.

Animals↗
PubMed2002

Three-dimensional reconstruction of confocal laser microscopy images to study the behaviour of osteoblastic cells grown on biomaterials.

The adhesion, spreading and cytoskeletal organization of osteoblastic cells seeded onto titanium and titania/hydroxyapatite composite coating (TiO2/HA) were studied using images acquired by confocal laser scanning microscopy. The fluorescence staining technique was employed to visualize actin cytoskeletal organization of cells, 2-D images were exhaustive when the cells were seeded at low density (in the first 24 h of incubation), but they were less clear when the cells proliferated and appeared stacked. Since the shareware software were not satisfactory, a new 3-D image reconstruction was developed using ordinary software and a model was obtained directly from the optical section set, in order to achieve a more realistic and faithful vision of morphological structures and to evaluate the behaviour of bone cells grown on materials. The results showed that the cells grown on titanium conform to the irregular substrate surfaces maximizing the contact between the cell membrane and the substrate and proliferate disposing close to each other. On the contrary, the osteoblasts seeded onto TiO2/HA coating develop clusters where the cells aggregated extending processes in order to establish intercellular connections. Cell aggregation is an early and critical event leading to cell differentiation and mineralization process and could be a first signal of the tendency of TiO2/HA coating to stimulate cell differentiation.

Biocompatible Materials↗
PubMed2001

An anorexic lipid mediator regulated by feeding.

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown. Here we show that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding.

Animals↗
PubMed2001

Hemispherodextrins, a new class of cyclodextrin derivatives, in capillary electrophoresis.

A capped cyclodextrin derivative (THCMH), called hemispherodextrin, was observed to behave as a very efficient chiral selector for a variety of phenoxyacid enantiomeric pairs, both at pH 6 and pH 9. The very low concentration necessary to obtain separation was particularly impressive. The behaviour of THCMH was compared with that of other hemispherodextrins and cyclodextrin derivatives and the conclusions are reported. Some interesting conclusions are drawn by comparing the behaviour of THCMH with that of other hemispherodextrins reported elsewhere.

Cyclodextrins↗
PubMed2001

New cyclodextrin derivatives as chiral selectors in capillary electrophoresis.

The separation of three pairs of enantiomeric herbicides has been successfully achieved by capillary electrophoresis at two different pH values in the presence of cyclodextrin derivatives previously synthesized in our laboratory. Two of these derivatives constitute a new class of receptor, the hemispherodextrins, in which a trehalose capping moiety is bonded to beta-cyclodextrin. Because of their peculiar structure hemispherodextrins have very promising characteristics and the low receptor concentration required to achieve separation deserves particular interest.

Algorithms↗
PubMed2001

Inducing or restraining demand: the market for night visits in primary care.

We analyse the demand for and the supply of night visits in primary care. We present a model of general practitioners (GPs) choice between meeting demand by making visits themselves or passing them to commercial deputising services. We extend previous models of demand management to allow for demand discouragement as well as demand inducement. Demand and supply equations are derived and estimated using 1984/1985-1994/1995 panel data for English primary care health authorities. Demand is not affected by the likelihood that the visit is made by a GP or a deputy, suggesting that patients do not perceive these visits as being of different quality. The introduction of differential fees for GP and deputy visits in April 1990 led GPs to increase their own visits and to reduce the number made by deputies. The fee change also led to demand being managed downward where GPs used deputies and to demand inducement where they met demand themselves.

Contract Services↗
PubMed2001

Preoperative autologous blood donation by elderly patients undergoing orthopaedic surgery.

BACKGROUND AND OBJECTIVES: To assess the feasibility of a programme of predeposit in elderly patients undergoing elective orthopaedic surgery. PATIENTS AND METHODS: We retrospectively studied 789 elderly patient candidates (> 65 years of age) for orthopaedic surgery (total hip and knee replacement and spinal surgery), who were undergoing a programme of preoperative autologous blood donation (PABD) in our city hospital between January 1990 and December 1998. RESULTS: Six hundred and eighty-eight patients (87.2%) were transfused with autologous blood; 128 (16.2%) also received allogeneic blood. Hip arthroplasty revision was characterized by the greatest blood consumption. The predeposit programme was discontinued in 96 patients (12.2%) because of the following complications: the onset of anaemia (11.0%); vasovagal reactions (0.5%); lack of venous access (0.4%); or cardiac complications (0.2%). No episodes of reaction to autologous transfusion were recorded. CONCLUSIONS: Our study confirms the feasibility of PABD in elderly patients undergoing elective orthopaedic surgery.

Aged↗
PubMed2001

Impact of payment method on behaviour of primary care physicians: a systematic review.

OBJECTIVE: To review the impact of payment systems on the behaviour of primary care physicians. METHODS: All randomised trials, controlled before and after studies, and interrupted time series studies that compared capitation, salary, fee-for-service or target payments (mixed or separately) that were identified by computerised searches of the literature. Methodological quality assessment and data extraction were undertaken independently by two reviewers using a data checklist. Study results were qualitatively analysed. RESULTS: Six studies met the inclusion criteria. There was considerable variation in the quality of reporting, study setting and the range of outcomes measured. Fee-for-service resulted in a higher quantity of primary care services provided compared with capitation but the evidence of the impact on the quantity of secondary care services was mixed. Fee-for-service resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but lower patient satisfaction with access to a physician compared with salary payment. The evidence of the impact of target payment on immunisation rates was inconclusive. CONCLUSIONS: There is some evidence to suggest that how a primary care physician is paid does affect his/her behaviour but the generalisability of these studies is unknown. Most policy changes in the area of payment systems are inadequately informed by research. Future changes to doctor payment systems need to be rigorously evaluated.

Capitation Fee↗
PubMed2001

Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology.

The endocannabinoids, a family of endogenous lipids that activate cannabinoid receptors, are released from cells in a stimulus-dependent manner by cleavage of membrane lipid precursors. After release, the endocannabinoids are rapidly deactivated by uptake into cells and enzymatic hydrolysis. Endocannabinoid reuptake occurs via a carrier-mediated mechanism, which has not yet been molecularly characterized. Endocannabinoid reuptake has been demonstrated in discrete brain regions and in various tissues and cells throughout the body. Inhibitors of endocannabinoid reuptake include N-(4-hydroxyphenyl)-arachidonylamide (AM404), which blocks transport with IC50 (concentration necessary to produce half-maximal inhibition) values in the low micromolar range. AM404 does not directly activate cannabinoid receptors or display cannabimimetic activity in vivo. Nevertheless, AM404 increases circulating anandamide levels and inhibits motor activity, an effect that is prevented by the CB1 cannabinoid antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A). AM404 also reduces behavioral responses to dopamine agonists and normalizes motor activity in a rat model of attention deficit hyperactivity disorder. The endocannabinoids are hydrolyzed by an intracellular membrane-bound enzyme, termed anandamide amidohydrolase (AAH), which has been molecularly cloned. Several fatty acid sulfonyl fluorides inhibit AAH activity irreversibly with IC50 values in the low nanomolar range and protect anandamide from deactivation in vivo. alpha-Keto-oxazolopyridines inhibit AAH activity with high potency (IC50 values in the low picomolar range). A more thorough characterization of the roles of endocannabinoids in health and disease will be necessary to define the significance of endocannabinoid inactivation mechanisms as targets for therapeutic drugs.

Amidohydrolases↗
PubMed2000

Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404.

The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg(-1) intraperitoneal, i.p. ) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg(-1), i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide.hydrochloride (SR141716A, 0.5 mg kg(-1), i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo.

Amides↗
PubMed2000

Bidirectional control of airway responsiveness by endogenous cannabinoids.

Smoking marijuana or administration of its main active constituent, delta9-tetrahydrocannabinol (delta9-THC), may exert potent dilating effects on human airways. But the physiological significance of this observation and its potential therapeutic value are obscured by the fact that some asthmatic patients respond to these compounds with a paradoxical bronchospasm. The mechanisms underlying these contrasting responses remain unresolved. Here we show that the endogenous cannabinoid anandamide exerts dual effects on bronchial responsiveness in rodents: it strongly inhibits bronchospasm and cough evoked by the chemical irritant, capsaicin, but causes bronchospasm when the constricting tone exerted by the vagus nerve is removed. Both effects are mediated through peripheral CB1 cannabinoid receptors found on axon terminals of airway nerves. Biochemical analyses indicate that anandamide is synthesized in lung tissue on calcium-ion stimulation, suggesting that locally generated anandamide participates in the intrinsic control of airway responsiveness. In support of this conclusion, the CB1 antagonist SR141716A enhances capsaicin-evoked bronchospasm and cough. Our results may account for the contrasting bronchial actions of cannabis-like drugs in humans, and provide a framework for the development of more selective cannabinoid-based agents for the treatment of respiratory pathologies.

Animals↗