Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study.

INTRODUCTION: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. METHODS: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. RESULTS: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-ß-lactamase producers, respectively. CONCLUSIONS: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Determinants of antibiotic prescription in children with adenovirus respiratory tract infections.

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4-7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42-103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01-1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25-11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00-1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65-100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41-2.89; p = 0.009) even when adjusted for CrP values.    Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: • Adenovirus infection is a common cause of fever and respiratory tract infections in children. • Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics.

Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case-Control Study.

BACKGROUND: Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. METHODS: This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. RESULTS: Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. CONCLUSIONS: Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

Effect of 1-y oral supplementation with vitaminized olive oil on platelets from healthy postmenopausal women.

OBJECTIVE: Olive oil is the main fat source in the Mediterranean diet and shows a protective role against aging and related diseases. Osteoporosis represents a serious health problem worldwide and is associated with an increased risk for fractures and mortality. Nutrition should be part of bone disease prevention strategies, especially in light of the aging population and the effect of diet on bone health. The aim of this study was to investigate whether oral supplementation with extra virgin olive oil (VOO) enriched with vitamins D3, K1, and B6 (VitVOO) is able to modify some physicochemical and functional plasma membrane properties and nitrosative stress markers status. METHODS: In this single-center, randomized placebo-controlled trial, 60 postmenopausal women were administered either VitVOO or placebo (PlaVOO). After 1 y of oral supplementation, platelet membrane fluidity changes, Na+/K+-ATPase activity, serum nitric oxide, and peroxynitrite levels were determined in participants. RESULTS: After 1 y (time 1), women taking VitVOO showed lower nitric oxide levels than those taking PlaVOO; the same trend was found for peroxynitrite levels. As far as membrane fluidity was concerned, a significant decrease in anisotropy of diphenylhexatriene and trimethylammonium-diphenylhexatriene at time 1 in VitVOO participants compared with PlaVOO was found. Finally, Na+/K+-ATPase activity showed a significant increase after VitVOO supplementation. CONCLUSION: The supplementation of VitVOO into the diet of postmenopausal women could represent a proper tool for platelet function and a useful strategy against nitrosative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells.

Des-acyl ghrelin is the unacylated form of the well-characterized appetite-stimulating hormone ghrelin. It affects a number of physiological processes, including increasing adipose lipid accumulation and inhibiting adipose tissue inflammation. Breast adipose tissue inflammation in obesity is associated with an increase in the expression of the estrogen biosynthetic enzyme, aromatase, and is hypothesized to create a hormonal milieu conducive to tumor growth. We previously reported that des-acyl ghrelin inhibits the expression and activity of aromatase in isolated human adipose stromal cells (ASCs), the main site of aromatase expression in the adipose tissue. The current study aimed to examine the effect of des-acyl ghrelin on the capacity of mouse macrophages (RAW264.7 cells) and human adipose tissue macrophages (ATMs) to stimulate aromatase expression in primary human breast ASCs. RAW264.7 cells were treated with 0, 10 and 100pM des-acyl ghrelin following activation with phorbol 12-myristate 13-acetate, and cells and conditioned media were collected after 6 and 24h. The effect of des-acyl ghrelin on macrophage polarization was examined by assessing mRNA expression of pro-inflammatory M1-specific marker Cd11c and anti-inflammatory M2-specific marker Cd206, as well as expression of Tnf and Ptgs2, known mediators of the macrophage-dependent stimulation of aromatase. TNF protein in conditioned media was assessed by ELISA. The effect of RAW264.7 and ATM-conditioned media on aromatase expression in ASCs was assessed after 6h. Results demonstrate des-acyl ghrelin significantly increases the expression of Cd206 and suppresses the expression of Cd11c, Tnf and Ptgs2 in activated RAW264.7 cells. Treatment of RAW264.7 and ATMs with des-acyl ghrelin also significantly reduces the capacity of these cells to stimulate aromatase transcript expression in human breast ASCs. Overall, these findings suggest that in addition to direct effects on aromatase in ASCs, des-acyl ghrelin also has the capacity to inhibit the macrophage-dependent induction of aromatase, and provides a novel mechanism for potential effects of des-acyl ghrelin to break the linkage between obesity and breast cancer.

Effect of 1-year dietary supplementation with vitaminized olive oil on markers of bone turnover and oxidative stress in healthy post-menopausal women.

Osteoporosis represents a serious health problem worldwide associated with an increased risk of fractures and mortality. Nutrition should form part of bone disease prevention strategies, especially in the light of the population ageing and the diet effect on bone health. Thus the study aimed at verifying whether 1 year of oral supplementation with either extra virgin olive oil (VOO) enriched with vitamins D3, K1 and B6 (VitVOO) or VOO used as placebo (PlaVOO) is able to modify some bone turnover and oxidative stress markers. Bone mineral density (BMD) was assessed in 60 healthy post-menopausal women together with the bone vitamin K status by measuring undercarboxylated osteocalcine (ucOC) plasma levels, the ratio between ucOC and carboxylated osteocalcine (UCR) and the relations with oxidative stress markers. After 1 year (T 1), subjects taking VitVOO showed lower ucOC levels than those taking PlaVOO; the same trend was found for UCR. As far as BMD is concerned, a significant increase in T-score at T 1 in VitVOO subjects compared to PlaVOO was found. All oxidative stress markers as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes showed a significant reduction after VitVOO supplementation, whilst plasma total antioxidant capacity values was significantly increased in VitVOO group compared to PlaVOO group at T 1. It might be suggested that the use of VitVOO in the diet of post-menopausal women could represent a proper tool for bone protection and a useful strategy against oxidative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Effects of in vitro supplementation with Syzygium cumini (L.) on platelets from subjects affected by diabetes mellitus.

The aim of this study was to assess the in vitro effects of Syzygium cumini (L.) (Sc) incubation on platelets from patients with diabetes, in order to test its efficacy as a potential adjuvant therapy. This study was performed on 77 patients with diabetes [29 in good (DMgc) and 48 in poor glycemic control (DMpc)] and 85 controls. In patients, platelets were analyzed at recruitment and after in vitro Sc incubation (final concentration of 200 µg/ml for 3 hours at 37 °C), whereas in controls only basal evaluation was performed. Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1-6-phenyl-1,3,5-hexatriene (DPH) were determined. Collagen-induced platelet aggregation was also evaluated. In vitro Sc activity counteracts oxidative damage, by improving platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it also enhances antioxidant system functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels both in whole samples and in DMgc and DMpc. In addition, a slight tendency towards collagen-induced platelet aggregation decrease after Sc was observed. However, all these parameters, even after improvement, did not reach the levels of control subjects. Our results suggest that Sc may have a preventive and protective effect in oxidative damage progression associated with diabetes mellitus and its complications. If our data will be confirmed, Sc supplementation might become a further tool in the management of this disease, especially in view of its easy availability, safety, low cost, and absence of side effects.

Oxytocin, its antagonist Atosiban, and preterm labor: a role for placental nitric oxide.

OBJECTIVE: The aim of the present study was to understand the role played by Atosiban, an oxytocin receptor antagonist, on trophoblastic human cells, and the molecular bases of its efficacy and safety in the treatment of preterm labor. NO, peroxinitrite production and NOS expression have been evaluated on placenta obtained from term and preterm labors. PATIENTS AND METHODS: We studied trophoblast cells isolated from selected placental tissue from 20 controls and 20 preterm patients after cesarean sections. Each sample was studied at basal state and after 2 hours incubation with oxytocin and Atosiban. RESULTS: Significant variations of NO levels, peroxynitrite production and iNOS and eNOS expression both in the preterm, term samples and in each of the considered groups were observed. In the control group Atosiban re-established NO levels that were reduced after incubation with oxytocin, while in preterm samples NO levels were not only re-established but, after incubation with Atosiban, significantly increased compared to basal levels. CONCLUSIONS: This confirms the beneficial role of Atosiban in prolonging the pregnancy of spontaneous labor at very early gestational periods. In conclusion, Atosiban might be an effective drug to prevent preterm labor, in the therapeutic approach to this pathology.

Erythroidine alkaloids: a novel class of phytoestrogens.

Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, ß-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-ß-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and ß-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only ß-erythroidine bound to ERß (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and ß-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens.

Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae.

The production of Klebsiella pneumoniae carbapenemases (KPCs) by Enterobacteriaceae has become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing K. pneumoniae (KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-control study in five large Italian hospitals. The case cohort consisted of adult inpatients whose hospital stay included at least one documented isolation of a KPCKP strain from a clinical specimen. For each case enrolled, we randomly selected two matched controls with no KPCKP-positive cultures of any type during their hospitalization. Matching involved hospital, ward, and month/year of admission, as well as time at risk for KPCKP isolation. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. During the study period, KPCKP was isolated from clinical samples of 657 patients; 426 of these cases appeared to be true infections. Independent predictors of KPCKP isolation were recent admission to an intensive care unit (ICU), indwelling urinary catheter, central venous catheter (CVC), and/or surgical drain, ≥ 2 recent hospitalizations, hematological cancer, and recent fluoroquinolone and/or carbapenem therapy. A Charlson index of ≥ 3, indwelling CVC, recent surgery, neutropenia, ≥ 2 recent hospitalizations, and recent fluoroquinolone and/or carbapenem therapy were independent risk factors for KPCKP infection. Models developed to predict KPCKP isolation and KPCKP infection displayed good predictive power, with the areas under the receiver-operating characteristic curves of 0.82 (95% confidence interval [CI], 0.80 to 0.84) and 0.82 (95% CI, 0.80 to 0.85), respectively. This study provides novel information which might be useful for the clinical management of patients harboring KPCKP and for controlling the spread of this organism.

Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features.

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na(+)/K(+)-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

Impact of gender on platelet membrane functions of Alzheimer's disease patients.

There are many evidences suggesting that oxidative stress is one of the earliest events in Alzheimer disease (AD) pathogenesis and plays a key role in the development of the AD pathology. The existence of substantial gender-related differences in the clinical features of AD has been recently confirmed (i.e. pathophysiologic features and epidemiologic trends). In addition, study results appear to indicate that the etiopathogenetic mechanisms of AD differ significantly in the 2 sexes. Based on previous results regarding changes in AD platelet plasma membrane, the purpose of the present study was to assess the impact of gender in the same model above reported. In particular we aimed at studying platelets from AD patients (M-AD and F-AD) and matched controls (M-C and F-C), divided into gender, by studying nitric oxide (NO) and peroxynitrite (ONOO(-)) production, the intracellular Ca(2+) concentration ([Ca(2+)]i), membrane Na(+)/K(+)-ATPase activity and fluidity. NO production was significantly elevated in platelets from both F-AD and M-AD compared to matched controls. M-AD showed NO production significantly higher than F-AD and it was the same between M-C and F-C. A similar trend was seen for ONOO(-). Platelets of both M-AD and F-AD had intracellular Ca(2+) concentrations significantly higher than F-C and M-C, while membrane Na(+)/K(+)-ATPase activity showed an opposite trend, but these differences are still significant. M-AD male subjects showed a significantly increased DPH fluorescence anisotropy (r) compared with controls, while for F-AD this discrepancy was not significant. The difference in DHP fluorescence anisotropy remained significant between M-AD and F-AD as well as between M-C and F-C. The TMA-DPH fluorescence anisotropy showed the same trend, but there were no significant differences between M-AD and F-AD, as well as between controls. The results of the current research support the conclusion that F-AD is not at greater risk than M-AD for oxidative stress injuries. Studies on gender differences could lead to a higher probability of improved health outcomes via better-targeted therapies.

Glutamate in vitro effects on human term placental mitochondria.

OBJECTIVE: Oxidative stress may affect the functionality of placental mitochondria, thus contributing to serious complications. For this reason research of protective substances is of great importance. Our aim was to evaluate, in mitochondria isolated from human term placentas, the effect of in vitro glutamate supplementation on their susceptibility to oxidation, on the chemico-physical characteristics of mitochondrial membranes, and on peroxidase and nitric oxide synthase (NOS) activities. METHODS: The study was performed on mitochondria isolated from 20 healthy human term placentas. Specific exclusion criteria were: conception by assisted reproduction, chromosomal or other fetal, uterine or placental anomalies, gestational diabetes, preeclampsia, intrauterine growth restriction (IUGR), a history of smoking and hypertension, proteinuria, renal, cardiovascular, hepatic, and endocrine disease, metabolic disorders, and current infection or history of all types of infection. RESULTS: Incubation with glutamate determined a reduced susceptibility to oxidative stress, an increase in mitochondrial membrane fluidity, and a decrease of both peroxidase and NOS activities. CONCLUSIONS: On the basis of the observed results, we can hypothesize a role for glutamate in the control of lipid peroxidation extent in physiological pregnancies, as well as in the prevention of free radical-linked complications that can affect the health of both mother and fetus.

Alterations of platelet biochemical and functional properties in newly diagnosed type 1 diabetes: a role in cardiovascular risk?

BACKGROUND: The involvement of platelets in the pathogenesis of diabetic vascular complications is supported by several studies. Type 1 diabetic (T1D) platelets show increased adhesiveness and aggregation related to a modification of nitric oxide synthase activity. Moreover, different cell types from diabetic patients showed a decreased membrane Na(+) /K(+) -ATPase activity, which might be involved in diabetic complications. The aim of this study was to investigate whether T1D at onset is able to induce alterations of platelet physicochemical and functional properties and whether these changes are affected by hyperglycaemia. METHODS: The study was performed on 50 young subjects: 30 patients (1-14 years) affected by T1D and 20 age- and gender-matched healthy subjects. We analyzed platelet membrane fluidity by fluorescent anisotropy of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene, Na(+) /K(+) -ATPase, nitric oxide, and peroxynitrite production. RESULTS: In T1D subjects, we observed an increased fluidity in the plasma membrane outer part and greater rigidity in the internal part compared with that in controls. Na(+) /K(+) -ATPase activity and nitric oxide levels were significantly reduced, while peroxynitrite production was increased compared with that in controls. Moreover, correlations found between the above parameters were correlated with fasting glycaemia and haemoglobin A(1c). CONCLUSIONS: T1D patients exhibit structural and functional modifications of platelet membrane properties and alterations of nitric oxide metabolism due to diabetes per se and not to chronic hyperglycaemia, insulin therapy, or ageing. These results support the hypothesis that oxidative attack could be an important early event in the pathogenesis of diabetic complications.

Interactions between lipoproteins and platelet membranes in obesity.

The aim was to investigate low-density lipoprotein (LDL) composition and Na(+)/K(+) adenosine triphosphatase (ATPase) and Ca(2+) ATPase activities and membrane fluidity measured by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical-physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na(+)/K(+) ATPase and Ca(2+) ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA-DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.

Platelet membrane fluidity and Na+/K+ ATPase activity in acute stroke.

Stroke is a consequence of a reduction in cerebral blood flow but the mechanisms involved in the production of ischemic damage are complex and probably not fully known. It is hypothesized that alterations in platelet membrane fluidity are directly related to the severity of the stroke as measured by the National Institute of Health Stroke Scale (NIHSS). Thus, the aim of the present study was to investigate Na+/K+ ATPase activity and platelet membrane fluidity, measured by fluorescent probes TMA-DPH and DPH in patients affected by ischemic stroke and controls in order to identify, if any, chemical-physical and/or functional modifications associated with cerebral ischemic damage. Patients were divided into three groups according to the presence of vascular risk factors (Diabetes Mellitus, Hypertension and Smoking) in order to evaluate the possible influence of each risk factor on the NIHSS score and both Na+/K+ ATPase activity and platelet membrane fluidity. Data showed a significant decrease in both Na+/K+ ATPase activity and platelet fluidity values in patients compared to controls. Moreover, all three groups showed a negative significant correlation between NIHSS and Na+/K+ ATPase activity and a positive significant correlation between NIHSS, TMA-DPH and DPH. In conclusion, the present data point out that alterations in the platelet membrane's chemical-physical (decreased fluidity) and functional properties (reduced Na+/K+ ATPase activity) rose proportionally with NIHSS increase. These modifications and their interaction with some vascular risk factors might be involved in the pathogenesis of ischemic damage development.

Cytotoxic effects induced by hexachlorobenzene in Squilla mantis (L.) (Crustacea, Stomatopoda).

Contamination of marine environments by hexachlorobenzene (HCB) represents a serious concern for potential consequences on ecosystem and human health. Despite this, information on cytotoxic effects on marine organisms is still largely lacking. In this study, we investigated cytotoxic effects induced by HCB on gonads and muscular tissue of Squilla mantis by analysing Na(+)/K(+)-ATPase activity and plasma membrane fluidity. This crustacean species was selected as a model for its habitat, trophic level, feeding behavior, and commercial exploitation for human consumption. Time course experiments revealed that low concentrations of HCB (i.e. 50 nM) determine an exponentially decrease of Na(+)/K(+)-ATPase activity and a significant modification of cellular membrane fluidity. Significant negative relationships between Na(+)/K(+)-ATPase activity and membrane fluidity were observed, suggesting that changes in the structure and packing of cellular membranes induced by HCB may be the primary factor affecting the activity of essential bilayer-associated enzymes. Overall these findings suggest that even small concentrations of HCB may determine important changes on cell metabolism with potential cascade effects on recruitment of this commercial species.