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Biomedical subjects

G Caimi

Publications and source records attributed to G Caimi.

At least 19 recordsLinked to original sources
PubMed2003

Polymorphonuclear leukocyte integrin pattern, at baseline and after activation, in type 2 diabetic subjects with macrovascular complications.

In vascular atherosclerotic disease and in diabetes mellitus few studies have evaluated the polymorphonuclear leukocyte (PMN) adhesion molecule pattern. In this study we examined the PMN integrin expression at baseline and after activation in controls and type 2 diabetic subjects with macrovascular complications (MVC). We enrolled 21 subjects with type 2 diabetes mellitus and macrovascular complications, localized in peripheral, coronary and cerebral sites. The patients had peripheral occlusive arterial disease, chronic cerebrovascular disease or coronary heart disease. We evaluated the expression of some PMN integrins (CD11a, CD11b, CD11c, CD18), using flow cytofluorimetry, at baseline and after in vitro activation with 4-phorbol-12-myristate-13 acetate. Type 2 diabetic subjects with MVC showed, compared to normals, an increase of CD11a and CD18 and a decrease of CD11b and CD11c. After activation, in PMN(s) of normal subjects, we found an increase in the expression of all adhesion molecules, while in PMNS of type 2 diabetic subjects with MVC we observed an increase of CD11b and CD11c and a decrease of CD11a. In type 2 diabetic patients with MVC the basal upregulation of CD11a and CD18 may be related to the PMN spontaneous activation, while the behavior of CD11b may depend on its self-consumption. After activation the CD11a modification may be due to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

Aged↗
PubMed2002

Polymorphonuclear leukocyte membrane fluidity, at baseline and after in vitro activation, in obesity with or without diabetes mellitus.

We studied a group of 28 obese subjects (mean age 38.2+/-13.5 years, body mass index 35.0+/-5.6 kg/m2) with insulin resistance demonstrated employing an euglycemic hyperinsulinemic clamp, subdivided into a subgroup with normal glucose tolerance (NGT) and a subgroup with type 2 diabetes mellitus (DM). We examined the polymorphonuclear leukocyte (PMN) membrane fluidity at baseline and after activation with 4-phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucylphenylalanine (fMLP). At baseline, PMN membrane fluidity was significantly decreased in both subgroups compared to normals. In obese subjects with NGT no correlation was found between this PMN determinant and the parameters reflecting the insulin-resistance degree (glucose disposal [M] and metabolic clearance rate of glucose [MCR]), while in type 2 DM subjects the PMN membrane fluidity was correlated to M and MCR. After activation with PMA and fMLP, no variation in PMN membrane fluidity was observed in normals, while in obese subjects with NGT an early decrease was present only after fMLP activation, and in obese subjects with type 2 DM there was a constant and significant decrease of this PMN parameter after activation with PMA and fMLP. Our interest in the study of the PMN membrane fluidity emerges from its known role in PMN function, especially considering that PMN cells, together with monocytes, may be mediators of vascular damage.

Adult↗
PubMed2002

Haemorheological profile in metabolic Syndrome.

Metabolic Syndrome (MetS) has been defined as a clinical condition including impaired glucose tolerance or diabetes mellitus and/or insulin-resistance, associated with two or more of the following components: arterial hypertension, central obesity, dyslipidaemia, microalbuminuria. In a group of subjects with MetS we examined the macrohaemorheological profile, demonstrating a significant increase of blood, plasma and serum viscosity and a decrease of whole blood filterability. The results show that in these subjects a secondary hyperviscosity condition is present, but also that several significant correlations are present between the haemorheological variables and some aspects of MetS, especially those reflecting central obesity (waist to hip ratio) and insulin-resistance. The altered haemorheological profile likely contributes to explain the high cardiovascular risk present in MetS, but it may also participate, through its influence on haemodynamic pattern, in the pathogenesis of insulin-resistance.

Adult↗
PubMed2002

Polymorphonuclear leukocyte integrin profile in diabetes mellitus.

We examined the polymorphonuclear leukocyte (PMN) integrin pattern in 45 diabetic subjects without macrovascular complications, including 21 subjects with type 1 and 24 with type 2 diabetes mellitus. The PMN adhesion molecules (CD11a, CD11b, CD11c, CD18) were evaluated using indirect immunofluorescence and a flow cytometer, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). At baseline, in diabetic subjects the phenotypical expression of CD11a and CD11b was significantly reduced and CD11c was increased, whereas CD18 was unchanged in comparison with normals. Considering type 1 and 2 diabetic subjects separately, CD11a was reduced and CD11c was increased in both subgroups, CD11b was decreased only in type 1 diabetics and CD18, decreased in type 1, was increased in type 2 subjects. After activation with PMA and fMLP, in normal subjects we observed a significant increase of all PMN adhesion molecules whereas in diabetic subjects only CD11c increased significantly with both activating agents, and CD11b increased only after PMA activation. In type 1 diabetic subjects only CD11c expression was increased, and in type 2 diabetic subjects an increase of CD11b (with PMA) and an increase of CD11c (with fMLP) were noted. In conclusion, we found in diabetic subjects of type 1 and 2 an altered behaviour pattern of PMN integrins both at baseline and, in particular, after in vitro activation. These data may help in explaining the role of PMN in the evolution of diabetic vascular complications.

Adult↗
PubMed2001

Granulocyte integrins before and after activation in acute ischaemic stroke.

We examined in 19 subjects with acute ischaemic stroke (AIS) the PMN integrin pattern (CD11a, CD11b, CD11c, CD18), using indirect immunofluorescence and adopting a flow cytometer, at baseline and during activation, prolonged for 5 and 15 min, with 4-phorbol 12-myristate 13-acetate (PMA). At baseline, an increase in the expression of CD11c and CD18 and a decrease in the CD11b were evident in AIS subjects compared to normals. After activation, we found in normals a constant and significant increase of all PMN adhesive molecules, while in AIS subjects, we found an increase in CD11b and CD18, a decrease in CD11a and no variation in CD11c. While the basal upregulation of CD11c and CD18 may depend on the PMN spontaneous activation or on the increase of cytokines, the decrease of CD11b may be due to its self-consumption. After activation, the decrease in CD11a noted in AIS may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

Acute Disease↗
PubMed2001

Leukocyte count, diabetes mellitus and age are strong predictors of stroke in a rural population in southern Italy: an 8-year follow-up.

Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.

Adult↗
PubMed2001

Endothelial perturbation in cystic fibrosis.

Cystic fibrosis (CF) is characterized by a persistent inflammatory state, which can be secondary to chronic pulmonary infection and may affect vascular endothelium. We measured circulating levels of von Willebrand factor (vWF), tissue-plasminogen activator (t-PA), and P-selectin in 20 CF patients and 20 healthy subjects. vWF, t-PA and P-selectin levels were significantly higher in CF patients. Endothelial perturbation (>2 SD increase in both vWF and t-PA) was present in 65% of CF patients. These patients displayed lower FEV1 values compared to individuals without endothelial perturbation and an inverse correlation between FEV1 and P-selectin levels was observed. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels were also increased in CF patients and significant direct correlations were found between TNF-alpha and vWF, t-PA or P-selectin levels. These results indicate that CF patients exhibit signs of endothelial dysfunction/perturbation, which are likely to be related to a persistent inflammatory state due to chronic pulmonary infection, and may play a role in the progression of this disease.

Adolescent↗
PubMed2000

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↗
PubMed2000

Polymorphonuclear leukocyte membrane fluidity before and after activation in subjects with insulin resistance.

The aim of this research was the evaluation of polymorphonuclear leukocyte (PMN) membrane fluidity in subjects with insulin resistance. Insulin sensitivity, in fact, may be influenced by plasma membrane fluidity. We enrolled 19 subjects with insulin resistance previously demonstrated during an euglycemic hyperinsulinemic clamp. PMN membrane fluidity was studied by labeling intact cells with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene and calculating the fluorescence polarization degree. The measurement was made before and after incubation of PMNs with two activating agents: 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). The baseline data showed a reduction of PMN membrane fluidity in subjects with insulin resistance. After PMN activation with PMA and fMLP, no significant variation in membrane fluidity was present in PMNs from normals, while in those from subjects with insulin resistance a slight decrease in PMN membrane fluidity was found only after activation with fMLP. The behavior of PMN membrane fluidity, before and after activation, distinguishes insulin-resistant subjects from normal controls, although the effect cannot be directly correlated with the degree of insulin resistance.

Adolescent↗
PubMed2000

Polymorphonuclear integrins, membrane fluidity, and cytosolic Ca(2+) content after activation in essential hypertension.

The purpose of this research was to obtain further information about the role of polymorphonuclear leukocytes in essential hypertension. These cells could be involved in the pathogenesis of organ injury. Thirty subjects (14 men and 16 women) with essential hypertension were enrolled. In these subjects we determined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate and N:-formyl-methionyl-leucyl-phenylalanine, the polymorphonuclear leukocyte membrane fluidity, obtained by labeling the cells with 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3, 5-hexatriene, cytosolic Ca(2+) concentration, obtained by marking the cells with Fura 2-AM, and integrin pattern (CD11a, CD11b, CD11c, and CD18), by using the indirect immunofluorescence with a flow cytometer. At baseline there was no difference in membrane fluidity between normal subjects and hypertensives, whereas hypertensives showed an increase in cytosolic Ca(2+) content and an increase of the phenotypical expression of CD11a, CD11b, and CD18. In normal subjects and in hypertensives, after activation, no variation was found in membrane fluidity and cytosolic Ca(2+) content. In normal subjects, after activation, we observed a significant increase of the expression of all adhesion molecules, whereas in hypertensives we found an increase of the expression of CD11b, CD11c, and CD18 but also a decrease of CD11a. The behavior of the polymorphonuclear leukocyte integrin profile may have several explanations, and in particular, the trend of CD11a after chemotactic activation may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance hypothetically present in this clinical condition.

Adult↗
PubMed2000

Acute ischemic stroke : polymorphonuclear leukocyte membrane fluidity and cytosolic Ca(2+) concentration at baseline and after chemotactic activation.

BACKGROUND AND PURPOSE: Several reports have considered the role of systemic leukocytes in acute ischemic stroke (AIS). Initially, greater attention was focused on the leukocyte count and subsequently on their adhesiveness, aggregation, rheology, and activation. The aim of this study was the evaluation of certain polymorphonuclear leukocyte (PMN) parameters, reflecting their rheology and activation, in subjects with AIS. METHODS: In a group of 19 subjects with AIS and in a control group of 18 subjects with asymptomatic vascular atherosclerotic disease, we evaluated the PMN membrane fluidity and cytosolic Ca(2+) concentration at baseline and after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). RESULTS: From the obtained data, it is evident that at baseline only PMN membrane fluidity distinguishes control subjects from AIS subjects. After PMN activation with PMA and fMLP, prolonged for 5 and 15 minutes, we found an increase in PMN cytosolic Ca(2+) concentration and a decrease in PMN membrane fluidity only in subjects with AIS. CONCLUSIONS: These findings emphasize that in subjects with AIS a functional alteration of systemic PMN cells is clearly expressed during chemotactic activation, although the mechanism of this abnormality is not yet explained.

Acute Disease↗