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Biomedical subjects

G Valentini

Publications and source records attributed to G Valentini.

At least 55 records · Page 3Linked to original sources

Increased expression of CD40 ligand in activated CD4+ T lymphocytes of systemic sclerosis patients.

CD40-CD154 interactions play a key role in regulating immune response and are involved in the development of some autoimmune diseases. We analysed the expression of CD154 antigen in CD3-activated PBMC from 10 systemic sclerosis (SSc) patients and 10 control subjects by immunofluorescence. PBMC from SSc patients showed an increased expression of this molecule, since, 6 h following CD3 stimulation, the percentage of CD154(+)cells was of 17. 53+/-2.0 (mean+/-SE) in control and 25.33+/-2.93 in patient cells (P< 0.03). The higher expression of CD154 antigen was ascribible to CD4(+)cells. The enhanced induction of CD154 following CD3 stimulation depended on protein synthesis, since was abolished when the cells were stimulated via CD3 in the presence of cycloheximide. By analysing the expression of the CD40-induced antigen CD80, we verified that a blocking anti-CD40 antibody inhibited CD80 appearance in SSc activated monocytes, indicating that CD154 molecule was functional. These results show an enhanced expression of a functional CD154 molecule in SSc CD4(+)activated T lymphocytes.

Adult↗

Right ventricular diastolic abnormalities in systemic sclerosis. Relation to left ventricular involvement and pulmonary hypertension.

OBJECTIVES: To investigate right ventricular diastolic function in systemic sclerosis (SSc) and its relation to clinical features of the disease. METHODS: Seventy seven unselected SSc patients and 33 healthy subjects were submitted to echocardiography and echo Doppler study to assess left and right systolic as well diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). In addition, the patients were investigated to define the SSc subset and the extent of skin and internal organ involvement. RESULTS: An abnormal right ventricular filling, as expressed by an inverted tricuspidal (Tr) E/A ratio (Tr E/A ratio <1), was detected in 31 of the 77 SSc patients (40%) and in 0 of the 36 controls ( p<0.001 ). All the 31 patients with an inverted Tr E/A ratio were found to have a PAP > 30 mm Hg. Twenty resulted to have an inverted mitral (Mit) E/A ratio (Mit E/A ratio <1), indicating an abnormal left ventricular filling. In multiple regression analysis, Tr E/A ratio resulted to be independently correlated to both PAP (r= -0.35;p<0. 003) and Mit E/A ratio (r=0.39;p<0.001). CONCLUSIONS: This study points out an impaired right ventricular filling in a significant percentage of SSc patients whatever the subset. This alteration is independently correlated to both PAP and left ventricular filling abnormalities.

Adult↗

Fluorescence imaging during photodynamic therapy of experimental tumors in mice sensitized with disulfonated aluminum phthalocyanine.

A fluorescence imaging system was used to monitor the emission of disulfonated aluminum phthalocyanine (AlS2Pc) during the photodynamic therapy (PDT) of murine tumors. Cells of the MS-2 fibrosarcoma were injected in mice in two compartments in order to cause the development of tumors in different host tissues. Two drug doses and two uptake times were considered. Moreover, the fluorescence of the AlS2Pc was excited using two wavelengths on the opposite sides of the absorption peak to detect a possible change in the absorption spectrum of the sensitizer induced by the PDT. In the tumors, the treatment induces a variation of the fluorescence intensity: in some mice a mild photobleaching takes place, in others a fluorescence enhancement occurs. Which effect predominates depends on the experimental conditions, even though a large spread of data was found amongst mice of the same group. In all mice, independently of the drug dose, uptake time or tumor compartment, a marked increase in the fluorescence signal takes place at the borders of the irradiated area. To quantify this effect we evaluated the ratio between the fluorescence intensities in the peritumoral area and in the tumor itself. This ratio increases monotonically during the PDT, showing a different behavior with the two excitation wavelengths. This indicates that the AlS2Pc absorption spectrum shifts toward shorter wavelengths as a result of the irradiation.

Animals↗

Reversible adult respiratory distress in primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APS) is a disorder caused by circulating antibodies reacting with biological membranes and characterized by recurrent thrombosis, chronic thrombocytopenia and miscarriages. It has been reported to occur either as a primary syndrome or secondary to systemic autoimmune disorders. We describe a case of primary APS in a young patient, in whom the clinical course was particularly severe and complicated by a respiratory distress syndrome. The patient was resistant to a number of treatments, and eventually responded to intravenous high dose corticosteroids.

Adolescent↗

Effects of the menstrual cycle on the red and near-infrared optical properties of the human breast.

Time-resolved reflectance and transmittance spectroscopy was applied to measure in vivo the absorption and transport scattering spectra of the female breast from 610 to 1010 nm. Three measurement configurations were used to probe different breast regions, and data were collected two or three times in each of the five phases of the menstrual cycle. The absorption spectra were best-fitted with a linear combination of the spectra of the main tissue constituents (water, lipids, oxy- and deoxyhemoglobin). This allowed us to evaluate percentage contents of water and lipids, total hemoglobin content and hemoglobin oxygen saturation. The scattering spectra were interpreted with a function derived from Mie theory, providing information on the density and average size of the tissue scatterers. Significant changes in the estimated variables were observed with measurement geometry, reflecting the heterogeneous nature of the breast, and with time, in agreement with expected physiological changes over the menstrual cycle.

Breast↗

[Titanium joints welded with laser and infrared techniques: comparative analysis of its microstructure].

BACKGROUND: Aim of the study is to compare microstructure of Titanium joints soldered with Laser and Infrared methods by performing SEM analysis, metallography and microhardness evaluation. METHODS: Wax specimens were separated in the middle area corresponding to the joint region, machined and then soldered. 40 Titanium samples were fused and divided in 2 groups of 20 samples each. First group was soldered by laser welding, second one by infrared brazing. SEM analysis and standard metallography were carried out at joined areas and unsoldered surfaces. Microhardness test was performed on longitudinally sectioned samples with 150 g load for 15 second up to 7 mm distance from the joined area. RESULTS: SEM photomicrographs revealed for group 1 a homogeneous metal-joint interface, without microporosities; for group 2 exhibited a distinct demarcation of metal joint interface. Metallography evaluation showed for laser joined samples only the presence of Titanium; infrared joined samples showed in soldered regions also Ni and Cu. Microhardness values detected at the joined surfaces seem to be higher for both considered groups. CONCLUSIONS: Laser joining method with exclusive presence of Titanium seems to be ideal for monometallism; both techniques exhibited microstructural changes in the heated surface layer.

Hardness Tests↗

[Malabsorption: current diagnosis trends].

The aim of this study was to review the problem of malabsorption, listing the main causes and the methods currently used to evaluate the gravity of the syndrome. The study was based primarily on data reported in the literature and on our personal experience at the Institute of Internal Medicine and Geriatrics at UCSC. Malabsorption is the term used to describe the defective passage through the intestinal mucosa of normal digestive products (this definition excludes the major chapter of maldigestion). Among the various methods currently used to study this problem, the authors list the most commonly used, highlighting two widely available instruments that are regarded as essential: anamnesis and objective examination. We have noticed that endless tests are often requested for a condition of malabsorption, which are not only expensive but also poorly tolerated by the patient, owing to the lack of a correct diagnostic approach based on a correct anamnesis and thorough objective examination. Lastly, we have put forward a number of guidelines based on personal experience to be followed when examining a patient with suspected malabsorption.

English Abstract↗

Decay of the GRB 990123 optical afterglow: implications for the fireball model

Broad-band (ultraviolet to near-infrared) observations of the intense gamma ray burst GRB 990123 started approximately 8.5 hours after the event and continued until 18 February 1999. When combined with other data, in particular from the Robotic Telescope and Transient Source Experiment (ROTSE) and the Hubble Space Telescope (HST), evidence emerges for a smoothly declining light curve, suggesting some color dependence that could be related to a cooling break passing the ultraviolet-optical band at about 1 day after the high-energy event. The steeper decline rate seen after 1.5 to 2 days may be evidence for a collimated jet pointing toward the observer.

Journal Article↗

Changes in concanavalin A-reactive proteins in neurological disorders.

Changes of glycosylation of cerebrospinal fluid proteins such as alpha2-macroglobulin, and prostaglandin D synthase were studied by lectin blotting, using concanavalinA, in multiple sclerosis (n = 42) and neuropathies (n = 20) in comparison to neurological controls (n = 22). The concanavalinA-reactivity of alpha2-macroglobulin, which was increased in the neuropathies but not in multiple sclerosis compared to controls, correlated with the total concanavalinA-reactivity in controls and neuropathies but not in multiple sclerosis, indicating that the protein could be abnormally glycosylated in the latter disease. Although the concentration and the concanavalinA-reactivity of prostaglandin D synthase were not significantly different in the three groups, the two parameters correlated only in neuropathies but not in controls or multiple sclerosis, probably due to the high heterogeneity of the protein. These changes deserve to be studied in further detail in view of their potential clinical applications.

Blood Proteins↗

Rapid detection of ornithine transcarbamylase activity by micellar electrokinetic chromatography.

A quantitative ultraviolet detection method for determining ornithine transcarbamylase (OTC-ase) activity using micellar electrokinetic chromatography (MEKC) is described. The method is based on the direct determination of citrulline formed upon enzymatic reaction. Using a background electrolyte consisting of 35 mM sodium tetraborate, pH 9.3, containing 65 mM sodium dodecyl sulfate (SDS), the peak of citrulline in the electropherogram was easily identified and integrated. This allowed us to determine the rate of formation of the reaction product and to calculate the kinetic parameter Km of the OTC-ase investigated. The capillary electrophoretic method developed was applied to the determination of OTC-ase activity in plasma samples for citrulline in the nanogram range.

Buffers↗

Micellar electrokinetic chromatography as a complementary method to sodium dodecyl sulfate-polyacrylamide gel electrophoresis for studying limited proteolysis of proteins.

Micellar electrokinetic chromatography (MEKC) has been utilized as an analytical method to perform investigations on limited proteolysis of proteins. To this purpose partial proteolysis experiments with a series of proteinases were performed, utilizing as model protein pyruvate kinase (PK) from Escherichia coli, an enzyme that is regulated allosterically by fructose 1,6-bisphosphate (FBP). Data obtained with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and MEKC were compared; the profiles generated by submitting digests of PK treated with different proteinases in the presence and absence of FBP to electrophoretic analysis provided a useful adjunct for a better understanding of the effects of the allosteric activator on the conformation of the model enzyme. MEKC was also found to be a convenient technique for determining the kinetics of substrate proteolysis.

Animals↗

Stabilization of rat serum proteins following oral administration of fish oil.

The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated by a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate that in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at 70 degrees C for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palmitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.

Administration, Oral↗

Myocardial infarction and death after caesarean section in a woman with protein S deficiency and undiagnosed phaeochromocytoma.

We describe the case of a 36-year-old woman, with a previous history of recurrent abortion due to protein S deficiency, undergoing an elective Caesarean section at 39-weeks gestation. During pregnancy no signs of hypertension or cardiovascular disease were reported, but at the end of the surgical procedure, the patient developed acute hypertension, leading to myocardial infarction, severe heart failure and death. The autopsy revealed a 2-cm undiagnosed phaeochromocytoma in the right adrenal gland. Clinical diagnostic features of phaeochromocytoma during pregnancy as well as the main therapeutic approaches suggested in the literature are discussed.

Abortion, Habitual↗

Anaesthesia for ultrasound guided oocyte retrieval: midazolam/remifentanil versus propofol/fentanyl regimens.

To evaluate the quality of intra-operative anaesthesia and recovery characteristics of two different anaesthesia regimens, 60 healthy women undergoing ultrasound guided oocyte retrieval for in vitro fertilization procedures were randomly allocated to receive either a propofol/fentanyl or a midazolam/remifentanil based anaesthesia. The surgical procedure was successful in all patients and no severe side effects were reported by any patient. Four patients in the midazolam/remifentanil group (13%) would not accept the same anaesthetic procedure for further in vitro fertilization treatment due to intra-operative awareness, while all propofol/fentanyl patients were prepared to accept the same procedure again (P < 0.05). Patients in the propofol/fentanyl group required manual ventilation more frequently through a facemask than those patients treated with the midazolam/remifentanil combination (50% and 30%, respectively; P < 0.05). The time to achieve an Aldrete's score of 10 was shorter in the midazolam/remifentanil patients (2 +/- 2 min) than in those who received propofol/fentanyl (4 +/- 2 min) (P < 0.001), but no differences were observed in the time required to be 'fit to discharge' from the post-anaesthesia care unit. We conclude that the use of a midazolam/remifentanil regimen is as effective and safe as a fentanyl/propofol regimen in patients undergoing transvaginal oocyte retrieval for in vitro fertilization procedures.

Adult↗

Changes of glycosylation of serum proteins in Sjögren's syndrome: correlation with interleukin-6 and soluble interleukin-2 receptor.

A strong increase of the affinity for concanavalin A (Con A) of serum alpha 2-macroglobulin, a non-acute-phase protein, was observed by lectin blotting in patients with Sjögren's syndrome (SS). On the contrary, the total Con A reactivity of serum proteins, measured by enzyme-linked lectin assay, was not augmented in SS, compared with normal donors, probably because positive changes of certain proteins were balanced by negative changes of others, as suggested by lectin blotting analysis. However, a significant increase of total Con A reactivity occurred in subjects with increased serum concentrations of soluble interleukin (IL)-2 receptor, compared with patients with normal concentrations of this marker of disease activity. On the other hand, the same parameter did not appear to be different in patients with normal or increased serum concentrations of IL-6, indicating that this cytokine was not probably responsible for the changes of glycosylation described here.

Adult↗

Inhibition of protein denaturation by fatty acids, bile salts and other natural substances: a new hypothesis for the mechanism of action of fish oil in rheumatic diseases.

Natural hydrophobic substances like bile salts (cholate, deoxycholate, chenodeoxycholate, lithocholate and their conjugates with glycine and taurine), fatty acids (caprylic, capric, lauric, myristic, palmitic, stearic, oleic, linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acid) were much more active (EC50 approximately 10(-4)-10(-5) M) than selected amino acids (EC50 > 10(-2) M) and inorganic salts (EC50 approximately 10(-1) M) in inhibiting heat-induced denaturation of human serum albumin in vitro. Fish oil, rich in n-3-polyunsaturated acids such as eicosapentaenoic acid and docosahexaenoic acid, administered p.o. (1 ml/kg) in the rat, protected ex vivo (after 2 hr) serum against heat-induced denaturation more than bendazac, a known antidenaturant drug. Thus, we speculated that the antidenaturant activity of fish oil may be partly (in addition to the known effect on endogenous eicosanoid composition) responsible for its beneficial effects in rheumatoid arthritis and other rheumatic conditions. In this connection, it is of note that the in vitro antidenaturant activity of fish oil fatty acids was higher than that of known antidenaturant drugs such as bendazac and bindarit and nonsteroidal anti-inflammatory drugs like phenylbutazone and indomethacin which could exert beneficial effects in chronic inflammatory conditions by stabilizing endogenous proteins.

Administration, Oral↗

Alterations of nutritional status in the main gastrointestinal pathologies.

An impairment of nutritional status up to real malnutrition can frequently be associated to gastrointestinal diseases. The diseases of the gastrointestinal tract can be divided into five groups: those hampering the nutrient physiological transit (especially neoplastic diseases); those affecting the intestinal mucosa (such as chronic inflammatory bowel disease); those determining intraluminal maldigestion; the hepato-biliary diseases and finally, the diseases of the pancreas. In order to correctly evaluate the nutritional status of an individual, besides the determination of the common biochemical parameters, body composition by direct and indirect techniques and energy metabolism by indirect calorimetry should be measured. Patients affected by Crohn's disease showed a lower fat mass content along with higher lipid oxidation compared to patients affected by ulcerative colitis. Patients with coeliac disease at diagnosis had a reduction in both fat and fat-free mass content along with an increased utilisation of carbohydrates as fuel substrate. There are many factors potentially leading to severe malnutrition in pancreatic diseases, especially in the acute form. Due to the primary role played by the liver in the metabolism of energy substrates, an impaired nutritional status might be commonly found in cirrhotic patients. In this connection, our group reported an increased energy expenditure and lipid oxidation, and an insulin-resistant state in compensated liver cirrhotic patients. These alterations seemed to precede and probably to lead to liver-disease-related malnutrition.

Journal Article↗