Fluidity and cytosolic Ca2+ concentration of circulating polymorphonuclear leukocytes at baseline in some chronic and acute clinical conditions: review of our survey

Abstract. Objective: In this mini-review we describe the behavior of polymorphonuclear leukocyte (PMN) membrane fluidity and of PMN cytosolic Ca2+ concentration in some chronic and acute clinical conditions. Methods: PMN membrane fluidity was evaluated employing the fluorescent probe Fura-2AM, and PMN cytosolic Ca2+ concentration was evaluated using the fluorescent probe TMA-DPH. Results: From the determination of these two parameters investigated on resting PMNs, an almost constant increase in PMN cytosolic Ca2+ concentration in chronic clinical conditions, such as vascular atherosclerotic disease with and without diabetes mellitus, essential hypertension, chronic kidney disease, and diabetes mellitus of both types, and a decrease in PMN membrane fluidity in acute clinical conditions, such as juvenile acute myocardial infarction and acute ischemic stroke, are evident. Conclusion: The possible reasons for this different behavior are analyzed on the basis of pathophysiological considerations

The importance of prognosis in geriatric patients attending the emergency department: a comparison between two common short geriatric assessment tools

Background: The use of short geriatric tools in the emergency department (ED) is increasing, but the literature is still conflicting. The aim of this study is to compare the precision and the accuracy of two short geriatric assessment tools to predict mortality in a cohort of older patients attending the ED. Methods: A retrospective study was conducted including patients ≥ 65 years, attending the ED and transferred to a medical assessment unit from February to July 2022. Clinical Frailty Scale (CFS) and Brief Multidimensional Prognostic Index (Brief MPI) were administered. The association between Brief MPI and CFS and mortality was analysed via area under the curve (AUC) with its 95% confidence intervals (CIs), the C-statistics and a multivariate Cox’s regression analysis, in the latter case reporting the data as hazard ratios (HRs) with their 95% CI. Results: Among the 579 patients enrolled (mean age: 77 years), both Brief MPI and CFS showed a good accuracy in predicting mortality (AUC: 0.72; 95% CI: 0.61–0.83 for Brief MPI; 0.754; 95% CI: 0.65–0.83 for CFS). The discrimination of Brief MPI and CFS in predicting mortality was excellent, since the C-index of the Brief MPI was 0.85 and of CFS = 0.84. In the multivariate analysis, the risk for mortality was significantly increased for frailer subjects (HR 4.65; 95% CI: 1.45–15.00 for Brief MPI > 0.66; HR = 9.24; 95% CI: 1.16–76.90 for CFS > 6). Conclusions: Brief MPI and CFS showed a good accuracy/precision to predict mortality in older patients attending the ED. Considering that they are quick to perform, their introduction in ED clinical practice could be extremely helpful

Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute myocardial infarction

In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in cardiovascular disorders and in particular in coronary artery disease and acute myocardial infarction (AMI). Now we examined this parameter in subjects with juvenile myocardial infarction at the initial stage and after 3 and 12 months. We enrolled 123 young subjects (112 men and 11 women, mean age 39.4\ub15.8 yrs) with AMI. The time interval between the AMI onset and the investigation was 13\ub17 days. The mean value of NLR observed in young AMI subjects was significantly increased compared to normal controls (N = 1.817\ub10.711; young AMI subjects = 2.376\ub10.873, p < 0.0001). NLR does not discriminate STEMI (2.427\ub10.878) and non STEMI (2.392\ub10.868) or diabetics (2.604\ub11.000) and non diabetics (2.324\ub10.853), but it differentiates smokers (2.276\ub10.853) and non smokers (2.837\ub11.072). NLR at the initial stage is not correlated with the number of cardiovascular risk factors or with the extent of the coronary disease. In this study we found a significant decrease of neutrophil count at 3 and 12 months later AMI without any significant variation of lymphocyte and consequently we observed a decrease in NLR at these two intervals of time in comparison with the initial stage. Despite some limitations present in this study, it is interesting to underline that also in juvenile myocardial infarction this low-cost haematological marker may be considered together with other inflammatory indicators

Leukocyte Rheology Before and After Chemotactic Activation in some Venous Diseases

AbstractObjective: to evaluate leukocyte rheology, polymorphonuclear leukocyte (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with post-phlebitic leg syndrome (PPS) and acute deep-venous leg thrombosis (DVT). Subjects: twenty-two subjects with leg PPS and 14 subjects with leg DVT. Methods: we evaluated the leukocyte filtration (unfractionated, mononuclear cells (MN) and PMN), the PMN membrane fluidity and the PMN cytosolic Ca2+ concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). Results: at baseline we observed a significant difference in the filtration variables of unfractionated and MN cells and in PMN cytosolic Ca2+ concentration. After activation, in normal subjects and subjects with PPS and DVT, a significant variation in PMN filtration at 5 and 15 minutes was evident. In normal subjects, no variation was present in PMN membrane fluidity or cytosolic Ca2+ concentration after activation. In subjects with PPS and DVT, we found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca2+ concentration. After PMN activation (at 5 and 15 min) Δ% of IRFR distinguished normal subjects from subjects with PPS and DVT, while no difference was found in Δ% of membrane fluidity or cytosolic Ca2+ concentration. Conclusions: there is a functional alteration of leukocytes in these patients whose mechanisms are not yet clear

Analysis of the correlations between oxidative stress, gelatinases and their tissue inhibitors in the human subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is commonly associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders. On the basis of this observation, our aim was to examine the oxidative status and the matrix metalloproteases (MMP) profile in a group of subjects with OSAS. We enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, who were subsequently subdivided in two subgroups according to the severity of OSAS (low grade = L-OSAS; high grade= H-OSAS). We measured the parameters of oxidative stress, such as lipid peroxidation, protein oxidation, total antioxidant status (TAS), nitric oxide metabolites (NOx), and the plasma concentrations of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). We found a significant impairment of oxidative status in H-OSAS compared to L-OSAS and higher plasma levels of MMP-9 and TIMP-1 in H-OSAS compared to L-OSAS. In this study we observed a positive correlation between TBARS and MMP-9, a positive correlation between PC and MMP-9, and a negative correlation between NOx and MMP-9, especially in the whole group of OSAS subjects. These data underline how strong interrelationships among some parameters of the oxidative stress, in particular those reflecting lipid peroxidation, protein oxidation and NOx, and MMP-9 are evident in OSAS subjects. All these information may be useful in the clinical practice keeping in mind the cardiovascular complications generally accompanying the obstructive sleep apnea syndrome

Erythrocyte deformability, plasma lipid peroxidation and plasma protein oxidation in a group of OSAS subjects

Considering that obstructive sleep apnea syndrome (OSAS) is usually associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders, our aim was to examine the erythrocyte deformability and the oxidative status in a group of OSAS subjects. We consecutively enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L = 21 subjects with AHI30). We evaluated the erythrocyte deformability, expressed as elongation index (EI) and the parameters of the oxidative status, such as lipid peroxidation (expressed as thiobarbituric acid-reactive substances TBARS) and protein oxidation (measured as carbonyl groups PC). In the entire group and in the two subgroups of OSAS subjects we found a decreased erytrocyte deformability at all shear stresses, not correlated with the plasmatic oxidative stress nor with the polysomnographic parameters. Lipid peroxidation was increased in the whole group and in the H subgroup of OSAS while protein oxidation showed a different trend. As in OSAS the osmotic fragility and the metabolism of the red cells seem to be not impaired, the oxidative damage to the red cell membrane proteins might be responsible for the reduced erythrocyte deformability. This rheological alteration, in addition to the increase in whole blood and plasma viscosity and to the erythrocyte hyperaggregation, could influence the microcircolatory profile in OSAS subjects

Lipid peroxidation and nitric oxide metabolites in a group of subjects with obstructive sleep apnea syndrome

It is known that in OSAS the plasma lipid peroxidation has an opposite behavior in comparison with nitric oxide metabolites. In the re-examination of our survey of OSAS infjects we calculated the ratio between thiobarbituric acid reactive infstances (TBARS) and nitric oxide metabolites (NOx) in relation to OSAS severity. The study has regarded 48 OSAS infjects infdivided in two infgroups according to the apnea/hypopnea index-AHI-(Low=21 infjects with AHI 30). From the obtained data it is evident that the TBARS/NOx ratio is significantly higher in the H infgroup compared to L infgroup as well as this ratio is reduced in L infgroup in comparison with the whole group of OSAS infjects. In the entire group of OSAS infjects the TBARS/NOx ratio results positively correlated with AHI and ODI and inversely correlated with mSO2

Lipid peroxidation and protein oxidation are related to the severity of OSAS

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with elevated cardiovascular morbidity and mortality. Considering that oxidative stress is involved in endothelial dysfunction and atherosclerosis development, our aim was to examine lipid peroxidation and protein oxidation, two parameters of oxidative status, in a group of subjects with OSAS. PATIENTS AND METHODS: We consecutively enrolled 48 patients (36 men and 12 women; mean age 49.7\ub114.6 yrs) with OSAS, subsequently subdivided according to the apnea/hy-popnea index (AHI) value in two subgroups: Low (L= 21 subjects with AHI30). We examined lipid peroxidation, expressed as TBARS, and protein oxidation, measured as carbonyl groups in plasma samples from fasting venous blood. RESULTS: We observed that TBARS and car-bonyl groups were significantly higher in subjects with AHI > 30 in comparison with the L subgroup and the whole group of OSAS subjects. In addition, we found that these parameters were positively correlated with neck and waist circumference, with the AHI value and with the oxygen desaturation index, and negatively correlated with the mean oxygen saturation. CONCLUSIONS: Lipid peroxidation and protein oxidation in OSAS patients are significantly correlated with the severity of the disease

Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 \ub1 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications