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Biomedical subjects

G Triolo

Publications and source records attributed to G Triolo.

At least 19 recordsLinked to original sources

Comparison between recombinant baculo- and adenoviral-vectors as transfer system in cardiovascular cells.

The development of effective gene-therapeutic applications for cardiovascular disorders is in part limited by the lack of appropriate delivery systems. In an attempt to overcome this deficiency, we investigated the ability of baculoviral vectors to transduce human cardiovascular cells, for which data are missing in literature. Additionally, baculovirus ability to transduce target cells was compared to that of an adenoviral vector, a well characterized and widely used viral vector. Transduction experiments, performed using baculo/adenoviral vectors expressing the enhanced green fluorescence protein, revealed that, under the experimental condition considered, baculoviruses but not adenoviruses efficiently transduce human coronary smooth muscle cells (hCSMC); an opposite behavior was noticed for human coronary endothelial cells (hCEC). Thus, baculoviral vectors are potentially indicated as transfer system in the treatment of coronary restenosis, where growth inhibitory genes should reach hCSMC but not hCEC. When used to transduce human cardiomyocytes and fibroblasts, both vectors behaved similarly. Finally, studies on cellular DNA replication revealed a more prolonged and pronounced negative effect on cells transduced by adenoviral compared to baculoviral vectors. Our data indicate that baculoviruses represent an attractive alternative to adenoviruses as transfer vectors in cardiovascular cells and that baculovirus have the potential to be used as gene transfer system in cardiovascular diseases such as restenosis.

Adenoviridae↗

IVIG in APS pregnancy.

For more than two decades, the intravenous administration of high doses of IgG pooled from the plasma of healthy donors (immune globulin therapy, also known as 'IVIG') has benefited patients with a variety of autoimmune disorders. A potential therapeutic role of IVIG in the prevention of thrombosis and of miscarriages in antiphospholipid syndrome (APS) has been postulated. Multicenter randomized controlled trials attempted to define the role of IVIG in preventing pregnancy complications in APS indicate that simple anticoagulation could not be completely satisfactory, and certain patient subgroups might take advantage of IVIG therapy alone or in combination with heparin.

Abortion, Habitual↗

Clinical manifestations of Behçet's disease in 137 Italian patients: results of a multicenter study.

OBJECTIVE: To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients. METHODS: We retrospectively studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/- SD] years) seen consecutively in nine different referral centers. The duration of follow-up at study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behçet's disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms. RESULTS: The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%), genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% and 57.9% versus 36.1%, respectively; p < 0.05). 61.6% of our patients were HLA-B51 positive. CONCLUSION: Behçet's disease in Italian patients is characterized by a variety of clinical manifestations in agreement with the medical literature. Panuveitis and posterior uveitis/retinitis occur more frequently in male patients.

Adult↗

Factors influencing pain, physical function and social functioning in patients with osteoarthritis in southern Italy.

The aim of this study was to assess factors influencing bodily pain (BP), physical function (PF) and social functioning (SF) in patients with osteoarthritis (OA) from southern Italy A total of 1,782 patients (mean age 66.08 years, 570 men and 1,212 women) with knee, hip, spine or hand OA underwent a structured assessment comprising demographic data and the Short Form 36 (SF-36) BP, PF and SF scales. Separate multiple linear regression models were employed for statistical analysis. The mean disease duration was 9.18 years and the mean body mass index (BMI) was 27.06. The mean BP, PF and SF scores of 34.93 (SD 19.37), 63.58 (SD 26.53) and 47.89 (SD 21.83) for the study subjects were substantially lower than those expected for the general Italian population. Subjects who were younger with a shorter disease duration and lower BMI had better PF and SF Younger subjects with a lower BMI and a longer disease duration had less BP. Female sex was associated with more BP, worse SF and better PF. In conclusion, demographic and disease-related factors influence BP, PF and SF in southern Italian patients with OA.

Age Factors↗

Prevalence of headache in patients with Behçet's disease without overt neurological involvement.

The aims of the present study were to evaluate the prevalence of headache and the frequency of different headache syndromes in patients with Behçet's Disease (BD) without neurological involvement and to investigate the relationship with other clinical, and behavioural variables. Twenty-seven BD patients and 27 control subjects underwent a validated semistructured questionnaire based on the International Headache Society criteria. Levels of anxiety and depression, disease activity, and current medication were collected. Headache occurred in 88.9% of BD patients. There was no difference in the prevalence of the different headache syndromes between BD patients and controls. Only migraine without aura (MwA) was significantly more frequent in BD patients than controls (44.4% vs. 11.1%, respectively, P= 0.013). No relationship was found between MwA and clinical, and behavioural variables. Among headache syndromes, MwA showed the highest frequency in BD. A vascular or neuronal subclinical dysfunction could justify this association. A careful interview for migraine might be included in the diagnostic work-up of BD.

Adult↗

Humoral and cell mediated immune response to cow's milk proteins in Behçet's disease.

OBJECTIVE: To investigate the humoral and cellular immune response against cow's milk proteins in Behçet's disease and to distinguish any behaviour during active or inactive disease. METHODS: Peripheral blood mononuclear cells from 16 patients and from eight normal controls were cultured in the presence of phytohaemagglutinin (PHA), beta-casein, beta-lactoglobulin, or chicken egg albumin. Interferon gamma (IFNgamma) and interleukin 4 (IL4) were measured in the culture supernatants by enzyme linked immunosorbent assay (ELISA). Serum samples from 46 patients with Behçet's disease and from 37 healthy subjects were also studied for antibody detection. Antibodies to beta-casein, beta-lactoglobulin, and chicken egg albumin were determined by ELISA. RESULTS: High IFNgamma but not IL4 levels were found in the supernatants of lymphocytes from patients with active disease cultured in the presence of cow's milk proteins. Levels were comparable with those obtained in cultures stimulated with PHA. A significantly higher level of anti-beta-casein and anti-beta-lactoglobulin IgG and IgA antibodies was found in patients with active Behçet's disease. No relation was found between their occurrence and the age of the patients, the duration of disease, or the presence of gastrointestinal abnormalities. Antibodies to chicken albumin were detected at low levels and with a prevalence similar to that of healthy subjects. CONCLUSION: The results indicate that an active immune response occurs in Behçet's disease. This response involves an increased frequency of antibodies to cow's milk protein and a strong Th1 polarisation after exposure to these antigens. The occurrence of these abnormalities supports a putative role for cow's milk proteins immune response in the pathogenesis of Behçet's disease.

Acute Disease↗

Identification of human DNA helicase V with the far upstream element-binding protein.

The properties of human DNA helicase V (HDH V) were studied in greater detail following an improved purification procedure. From 450 g of cultured cells, <0.1 mg of pure protein was isolated. HDH V unwinds DNA unidirectionally by moving in the 3' to 5' direction along the bound strand in an ATP- and Mg(2+)-dependent fashion. The enzyme is not processive and can also unwind partial RNA-RNA duplexes such as HDH IV and HDH VIII. The M:(r) determined by SDS-PAGE (66 kDa) corresponds to that measured under native conditions, suggesting that HDH V exists as a monomer in the nucleus. Microsequencing of the purified HDH V shows that this enzyme is identical to the far upstream element-binding protein (FBP), a protein that stimulates the activity of the c-myc gene by binding specifically to the 'FUSE' DNA region localized upstream of its promoter. The sequence of HDH V/FBP contains RGG motifs like HDH IV/nucleolin, HDH VIII/G3BP as well as other human RNA and DNA helicases identified by other laboratories.

Amino Acid Sequence↗

Hemofiltration reduces the serum priming activity on neutrophil chemiluminescence in septic patients.

BACKGROUND: Priming of the polymorphonuclear neutrophil (PMN) response has been implicated in the activation of oxidative burst and tissue injury in patients with septic shock and acute renal failure (ARF). This study evaluated whether hemofiltration (HF) removes substances able to enhance the oxidative burst of PMNs. METHODS: Chemiluminescence (CL) priming activity induced by sera and ultrafiltrates of seven patients with septic shock, multiorgan dysfunction syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF group) was evaluated on normal human PMNs stimulated with bacterial formyl-methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating factor (PAF), and CL priming activity at the beginning (T0), and after four hours (T4) of treatment. RESULTS: Preincubation of normal human PMNs with sera and ultrafiltrates from septic patients induced a potent priming of CL activity in subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood concentrations of IL-8 and CL PMN-priming activity significantly decreased during the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930 (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the ARF/HF group, a significantly positive correlation between CL PMN-priming activity and IL-8 concentrations was observed. The CL priming activity in blood and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did not affect CL priming activity. In the control/HF group, the CL PMN-priming activity was significantly lower than in the ARF/HF group and was independent of IL-8. CONCLUSIONS: Sera from septic patients demonstrate an enhanced CL priming activity on PMNs. This activity is reduced by ultrafiltration and is due, at least in part, to ultrafiltered IL-8.

Acute Kidney Injury↗

Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells.

AIMS/HYPOTHESIS: This study examines whether increased glucose concentrations are responsible for a decreased expression of membrane regulators of complement activation molecules. The effect of high glucose in determining an increase in membrane attack complex deposition on endothelial cells was also investigated. METHODS: Endothelial cells were isolated from umbilical cord tissue, cultured in the presence of increased concentrations of glucose, and the expression of CD46, CD55, and CD59 was detected by ELISA (enzyme-linked immunosorbent assay) and by flow cytometry. Glucose-treated endothelial cells were also incubated with antiendothelial cell antibodies and fresh complement to assess the amount of membrane attack complex formation. RESULTS: High concentrations of glucose decreased the expression of CD59 and CD55 by endothelial cells in a time-dependent and glucose concentration-dependent manner without affecting CD46 expression. High concentrations of soluble CD59 were found in the supernatants of cells treated with high glucose. The decrease in CD59 expression induced by high glucose concentrations was reversed by coincubation of cells with a calcium channel blocking agent (Verapamil). All of these effects were not reproduced by osmotic control media. Cells treated with concentrations of high glucose were more susceptible to complement activation and membrane attack complex formation after exposure to antiendothelial cell antibodies. CONCLUSION/INTERPRETATION: We speculate that hyperglycaemia could directly contribute to a loss of CD59 and CD55 molecules through a calcium-dependent phosphoinositol-specific phospholipase C activation and subsequent regulation of cell wall expression of GPI-anchored proteins. This phenomenon could facilitate the activation of a complement pathway and could play a part in the aetiology of endothelial dysfunction in diabetes.

Antigens, CD↗

Do immune complexes formed with autoantibodies have a role in the maintenance of immune homeostasis through interaction with FC receptors.

Natural autoantibodies play an important regulatory role in the maintenance of immune homeostasis. They act as a first line of defense against environmental pathogens like toxins, bacteria and erythrocytes. In humans they are mainly produced by CD5+ B cells that are under the control of a regulatory T cell population. Fc-gamma receptors are involved in antigen recognition and signal transduction and tuning, and some of the members of the FcR family have structural similarity to MHC molecules; they may interact with multiple Ig ligands and with non-Ig ligands. We discuss the interactions between immune-complexes formed with natural autoantibodies and Fc-gamma receptors and suggest that such interactions may affect self-recognition in the thymus and regulate immune homeostasis.

Antigen-Antibody Complex↗

[Research potential of a regional registry].

BACKGROUND: The need for data bank gathering information in dialysis patients is as old as dialysis. Dialysis Registries presently active are characterized by different policies of data gathering (large vs small number of information) and of use (research vs economical or clinical purposes). Aim of the work was a discussion on the use of a Regional Registry (RPDT, Regional Registry of Dialysis and Transplantation of Piedmont, Italy), gathering since 1981 a wide set of information (about 80 items) on all patients treated in a relatively small area (about 4,300,000 inhabitants). METHODS: Two researches were selected: the first includes patients treated for > or = 20 years by RRT. Cases were identified on the basis of RPDT data and an inquiry regarding all patients was performed, with specific interest on comorbidity. The second includes diabetic patients on regular RRT, a sample of which was further analyzed in high detail. RESULTS AND CONCLUSIONS: While a Regional Registry, even gathering a wide set of data is unable to answer to the most qualitative questions, such as quality of life, its archives are a powerful tool to identify cases. Furthermore, ad hoc inquiries may represent a way to control quality of data or to test new fields to be studied. In the case of patients with long RRT follow-up, comorbidity questions were tested before being included on RPDT. In the case of a sample of diabetic patients, type of diabetes and cause of ESRD were controlled. This biunivocal relationship between clinical work-up and epidemiological archives may often interest future perspectives.

Adult↗

[Epidemiologic analysis of the incidence of new diabetic patients on dialysis as a basis for a clinical study].

BACKGROUND: Aim of this study is to analyse the incidence of diabetic patients starting dialysis in Piedmont (Italy) during the period 1981-1996 and to evaluate, in a subgroup of patients, the causes of uremia (diabetic nephropathy or other), and the type and seriousness of comorbid factors, in order to define the clinical conditions and try to explain the causes incidence increase. METHODS: Data are taken from the RPDT (Regional Registry of Dialysis and Transplantation of Piedmont). RESULTS: Total incidence of new patients starting dialysis in this Region increased from 65 pmp in 1981-1982 to 116 pmp in 1995-1996 and the mean age increased from 55.4 +/- 15.5 years in 1981-1982 to 61.5 +/- 15.6 in 1995-1996; 49% of patients had at least one of the 13 conditions of comorbidity considered by the Registry (including severe vascular, cardiac, systemic diseases and diabetes). In the same period the incidence of diabetic patients increased from 6 pmp (1981-1982) to 19 for males and 12 pmp for females (1995-1996); this increase is higher for males and limited to patients with age > or = 60 years (for example: group 70-79 years from 7 to 56 pmp). A study performed in a group of 64 patients (52 type 2 and 12 type 1) showed the incidence of multiple comorbid factors: the most important in type 2 are vascular diseases (44/52) and heart diseases (20/52); blindness and amputations are relatively rare (2 each). An important comorbid factor in type 1 diabetes is blindness (3/12) and in this group the most frequent cause of uremia is diabetic nephropathy (DN) (9/12); in the group of type 2 patients nephroangiosclerosis and a clinical picture of progressive renal failure, without nephrotic syndrome, represents 48% of all diagnoses. CONCLUSIONS: These results underline the necessity of a strict collaboration with diabetologists and of an improvement of dedicated structures in order to meet the increase of this critical population.

Adult↗

Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet's disease: moderate correlation with anti-endothelial cell antibodies and serum myeloperoxidase levels.

We studied the in vitro E-selection expression of endothelial cells treated with sera from patients with Behçet's disease (BD) and factors (anti-endothelial cell antibodies, anti-neutrophil cytoplasmic antibodies, cytokines, and myeloperoxidase (MPO) that may contribute to adhesion molecule expression. A total of 21 patients with BD and 27 healthy controls were studied. In vitro E-selectin endothelial cell expression was investigated by ELISA after HUVEC incubation with sera or purified IgG from patients with BD and controls. Increased E-selectin expression was observed when endothelial cells were incubated with sera from patients with active disease or from patients with circulating anti-endothelial cell antibodies and high levels of plasma myeloperoxidase. Abnormalities of endothelial cell function have been suggested to play a role in the occurrence of vascular damage in BD. Our findings suggest that anti-endothelial cell antibodies and neutrophil hyperactivity, as inferred from the high plasma MPO levels in patients with active disease, may explain endothelial cell activation and neutrophil accumulation in vascular lesions.

Adult↗

IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus; induction of adhesion molecule expression in cultured endothelial cells.

AECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of < 1 year duration and those with long-standing disease had the highest levels of these antibodies. Inhibition studies suggest that at least part of the AECA reactivity is due to cross-reactive anti-ssDNA antibodies. AECA-positive sera were able to increase intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was also found to accompany raised E-selectin expression. Soluble ICAM-1 and E-selectin were also found to be increased in the sera of AECA-positive patients. An effect of AECA on endothelial cell function is suggested in diabetes mellitus.

Adolescent↗

[Cachexia during dialysis].

In the Italian language, the term cachexia is a rather picturesque synonym of "marasma senile", "senile marasmus", an old definition involving not only old-age, but specifically senility, the end of the ageing process and marasmus, a stagnant and hopeless situation in which all superior organised functions have disappeared. The problem of cachexia during dialysis is complex and several discordant opinions exist at this regard, partly accounted by different definitions of this sluggish entity (or non entity). Actually, the basic question is very simple: is cachexia the cause or the effect of failure of dialysis treatment? The aim of this study was an evaluation of epidemiological data from the Dialysis and Transplantation Registry of Piedmont, a northern Italian Region with about 4,350,000 inhabitants, 22 public dialysis Centers, open acceptance to dialysis since the mid seventies, a multiple choice dialysis system developed in the eighties. In the period 1981-1995, 764 patients died in conditions of cachexia. This figure is 20.9% of all deaths recorded, 27.4% over age 65 and 34.7% over age 75. Despite a likewise significant increase in age and presence of comorbid factors, an improvement of patients survival, that reach statistical significance in the old age group (> or = 65 yrs), was observed.

Aged↗

Reasons for producing guidelines on anemia of chronic renal failure: dialysis outcome quality initiative of the National Kidney Foundation.

Guidelines for the treatment of anemia in chronic renal failure (CRF) patients were recently published by NKF-DOQI. The background was provided by the fact that anemia in CRF patients fulfills all the criteria requested for the outlining of guidelines. In fact: 1) anemia is a clinically relevant problem for CRF patients; 2) it may be prevented by adequate erythropoietin (EPO) therapy; 3) a great variability in its management exists, not only concerning the optimal hematocrit (HCT) level, but also the treatment schedule as well as iron supplementation. More than eight hundred forty five scientific articles were retrieved in full text, eventually leading to 530 structurally reviewed papers (349 cited in the final text) thus providing the basis for the strength of recommendations (evidence or opinions): all topics were subdivided into 7 main issues (diagnostic and therapeutic). Main results were the following: HCT, hemoglobin (Hb), red blood cell, serum iron binding capacity, percent transferrin saturation (TSAT) and serum ferritin (FERR), to evaluate the degree of anemia and iron status; HCT 33 to 36% and Hb 11 to 12 g/dl as possible target levels; TSAT >20% and FERR >100 ug/dl as acceptable lower values for iron status; oral iron administration not <200 mg/day of elemental iron and intravenous iron 50-100 mg/week or 500-100 mg/month (for patients on predialysis or peritoneal dialysis) as therapeutic schedules; subcutaneous route for EPO administration at 80-120 U/kg body weight/week as starting doses. Some issues may be debatable, such as, the underestimation of dialysis efficacy among the causes of inadequate response to EPO as well as the risk of thrombosis among the possible side effects of EPO therapy, or the lack of recommendation for upper limits of FERR values. However, this exhaustive study is an important demonstration of efforts to improve the quality of care in CRF patients.

Anemia↗