Clinical role of lung ultrasound for diagnosis and monitoring of COVID-19 pneumonia in pregnant women.

Lung ultrasound has been suggested recently by the Chinese Critical Care Ultrasound Study Group and Italian Academy of Thoracic Ultrasound as an accurate tool to detect lung involvement in COVID-19. Although chest computed tomography (CT) represents the gold standard to assess lung involvement, with a specificity superior even to that of the nasopharyngeal swab for diagnosis, lung ultrasound examination can be a valid alternative to CT scan, with certain advantages, particularly for pregnant women. Ultrasound can be performed directly at the bed-side by a single operator, reducing the risk of spreading the disease among health professionals. Furthermore, it is a radiation-free exam, making it safer and easier to monitor those patients who require a series of exams. We report on four cases of pregnant women affected by COVID-19 who were monitored with lung ultrasound examination. All patients showed sonographic features indicative of COVID-19 pneumonia at admission: irregular pleural lines and vertical artifacts (B-lines) were observed in all four cases, and patchy areas of white lung were observed in two. Lung ultrasound was more sensitive than was chest X-ray in detecting COVID-19. In three patients, we observed almost complete resolution of lung pathology on ultrasound within 96 h of admission. Two pregnancies were ongoing at the time of writing, and two had undergone Cesarean delivery with no fetal complications. Reverse transcription polymerase chain reaction analysis of cord blood and newborn swabs was negative in both of these cases. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

In vitro effects of fermented papaya (Carica papaya, L.) on platelets obtained from patients with type 2 diabetes.

BACKGROUND AND AIM: Oxidative stress is associated with insulin resistance pathogenesis, insulin secretion deficiency, and complication onset. Fermented papaya preparation (FPP), a dietary supplement obtained by fermentation of the papaya fruit, may be used as an antioxidant in the prevention of diabetic complications. METHODS AND RESULTS: Platelets from 30 patients with type 2 diabetes mellitus (DM 2) and 15 healthy subjects were analyzed to evaluate the in vitro effects of FPP incubation. Na(+)/K(+)-adenosine triphosphatase (ATPase) activity, membrane fluidity, total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, and conjugated diene levels were determined. In vitro FPP incubation improved platelet function, by enhancing Na(+)/K(+)-ATPase activity and membrane fluidity, and ameliorated the antioxidant system functionality, through an increase in TAC and SOD activity and a parallel decrease in conjugated diene levels in patients with DM 2. CONCLUSION: Our data suggest that the incubation with FPP may have a protective effect on platelets from patients with DM 2, by preventing the progression of oxidative damage associated with diabetes and its complications.

Outpatient parenteral antimicrobial therapy (OPAT) from an emergency model applied during the COVID-19 pandemic to standard of care: Preliminary lessons from our experience.

OBJECTIVES: We wish to report on our experience of OPAT during the first two years of the COVID19 outbreak. PATIENTS AND METHODS: We recorded data on all patients treated in the OPAT regimen in 2020 and 2021 and compared overall trends, use of carbapenems and saved days of hospitalization. RESULTS: The OPAT model enabled us to ensure the administration of first choice antibiotic therapy to 239 patients with an increase of 21.3% from 2020 to 2021 (108 vs 131). Applying this model, we also recorded a reduction in the use of carbapenems from 33% in 2020 to 26% in 2021 and a total of 3041 recovery days saved in 2021.The clinical cure rate reached 94%. Few adverse events occurred (35/239; 14.6%), and they did not require hospitalization. CONCLUSION: OPAT is a safe, efficacious, and cost-effective model that functioned effectively during the COVID-19 crisis and could become the standard of care for the treatment of selected patients.

Effect of consumption of dark chocolate on oxidative stress in lipoproteins and platelets in women and in men.

The goal of this research was to investigate the effects of 3 weeks consumption of 50 g flavonoid-rich dark chocolate on lipoprotein oxidative stress in vitro and in vivo in 25 women compared to 25 men. Levels of thiobarbituric acid-reactive substances, conjugated dienes and hydroperoxide levels in HDL and LDL before and after consumption of dark chocolate were determined. Moreover in platelets of the same subjects NO and peroxynitrite levels were studied. TBARs concentration in women's HDL decreased by 26.7% while in men's HDL 23.4%; lipid hydroperoxides decreased in women's HDL by 62.8% while in men's HDL they decreased by 21.1%. Conjugate diene formation decreased in women's HDL by 55.9%, while in men's HDL it decreased by 49.2%. Moreover TBARs concentration decreased in women's LDL by 26.7% after supplementation and in men's LDL by 21.6%; lipid hydroperoxides decreased in women's LDL by 83.6% while in men's LDL they decreased by 64.7%. Moreover conjugate diene formation decreased in women's LDL by 48.2%, while in men's LDL it decreased by 21.6%. After supplementation peroxynitrite values decreased in women by 24% and in men by 18.6% while NO increased after supplementation by 15.7% compared to basal determination in women, and by 32.2% in men. This study showed that a short-term intake of dark chocolate might improve the lipoprotein profile in healthy humans, more so in women than in men, and this might exert a protective effect on the cardiovascular system.

Point-of-Care Lung Ultrasound findings in novel coronavirus disease-19 pnemoniae: a case report and potential applications during COVID-19 outbreak.

An outbreak of a novel coronavirus disease-19 (nCoV-19) infection began in December 2019 in Wuhan, China, and now involved the whole word. Several health workers have been infected in different countries. We report the case of a young man with documented nCoV-19 infection evaluated with lung ultrasound and discuss potential applications of lung ultrasound in this setting. Lung ultrasound allowed the identification of nCoV-19 infection at bed-side. Moreover, lung ultrasound can have several other advantages, such as reduced health worker exposition to infected patients, repeatability during follow-up, low-costs and easier application in low-resource settings.

Sialic acid and sialidase activity in acute stroke.

Stroke is a heterogeneous syndrome caused by multiple disease mechanisms, resulting in a disruption of cerebral blood flow with subsequent tissue damage. It is well known that erythrocytes have a large amount of sialic acid and could represent a model to investigate changes occurring in a pathology like stroke. The aim of this study was to investigate a possible relationship among erythrocyte membrane, plasma and sialic acid content. The possible impact of the sialic acid content and the activity of sialidase on stroke severity was also evaluated. The study population consisted of 54 patients with a first stroke and of 53 age-and sex matched healthy volunteers. The total bound sialic acid was substantially decreased in patients. There was a significant correlation between the sialidase activity values and the severity of the neurological deficit defined by the National Institute of Health Stroke Scale. This study shows that low sialic acid erythrocyte concentrations with contemporary high sialic acid plasma levels and elevated sialidase activity can be considered as markers of ischemic stroke. Further investigations are needed to clarify the possible role of these biochemical changes in producing and sustaining cerebral ischemic damage.

Role of raloxifene on platelet metabolism and plasma lipids.

BACKGROUND: This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non-obese postmenopausal women. The data were compared to untreated subjects. MATERIALS AND METHODS: Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment. RESULTS: A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high-density lipoprotein cholesterol and a decrease of total cholesterol and low-density lipoprotein cholesterol were observed versus baseline values (P < 0.05). A significant positive correlation was observed between high-density lipoprotein cholesterol and platelet NO (r = 0.76, P < 0.005) in the raloxifene group. CONCLUSION: Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator.

Plasma levels of nitric oxide and stroke outcome.

Production of reactive oxygen species after cerebral blood flow disruption may enhance tissue damage through multiple molecular pathways. Changes in nitric oxide (NO) metabolism and oxidative stress status were investigated in 47 patients with ischemic stroke by measuring plasma nitric oxide (NO) and peroxynitrite (ONOO(-)) levels.A correlation was sought between these two parameters and i) baseline stroke severity based on the National Institute of Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS changes from entry (T(0)) to 30 days after symptom onset (T(1)). The control group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels of ONOO(-) (arbitrary fluorescence number +/- SD) were significantly higher in patients (7.70 +/- 1.71 vs 5.35 +/- 0.69, p < 0.001), whereas mean NO levels (nmol/mg protein) were significantly higher in controls (115.40 +/- 12.40 vs. 51.10 +/- 12.50, p < 0.001). Plasma ONOO(-) was significantly higher among patients with non-lacunar stroke (8.48 +/- 1.50 vs. 6.95 +/- 1.58 in those with lacunar stroke; p = 0.001), whereas NO levels were significantly higher among lacunar stroke patients (60.00 +/- 7.86, vs. 41.77 +/- 9.29 in patients with nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that changes in NO metabolism may be considered as markers of brain injury in patients with ischemic stroke. Further work is needed to establish whether the amount of biochemical changes related to oxidative stress may influence outcome in these patients.

Nitric oxide and peroxynitrite platelet levels in women with small-for-gestational-age fetuses.

OBJECTIVE: The placenta produces reactive oxygen species (ROS) including nitric oxide (NO) and peroxynitrite (ONOO(-)) that have pronounced effects on placental function. Excessive ROS production may occur in pathological pregnancies, such as those complicated by small-for-gestational-age (SGA) fetuses. DESIGN: The aim of the present work was to study NO and ONOO(-) levels in platelets of pregnant women with SGA fetuses compared with a control group. SETTING AND POPULATION: The study was performed on 30 pregnant women with SGA fetuses (SGA group) and on 30 healthy pregnant women (appropriate-for-gestational-age [AGA] group) matched for maternal and gestational age. All women included in this study were in the third trimester of pregnancy. METHODS: Platelets were isolated by differential centrifugation. NO metabolites, after enzymatic conversion followed by the Griess reaction, were measured as nitrite by spectrophotometric detection. Peroxynitrite (ONOO(-)) levels were evaluated using the fluorescence probe 2,7-dichlorofluorescein diacetate (DCFDA). MAIN OUTCOME MEASURES: The following determinations were made: platelet nitric oxide and peroxynitrite levels in the SGA group and controls; inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and nitrotyrosine (N-Tyr) expression in the same groups. RESULTS: Our results show that both platelet NO and ONOO(-) levels were significantly higher in the SGA group than in the controls. CONCLUSION: Increased platelets levels of nitric oxide and peroxynitrite might play a role in the pathophysiology of intrauterine growth restriction. Further investigations are in progress to clarify if these molecules are pathogenetic factors, an epiphenomenon or a pathophysiological marker.

In vitro effects of resveratrol on oxidative stress in diabetic platelets.

To evaluate the in vitro effects of resveratrol (RSV) incubation on platelets from compensated and decompensated diabetic patients in order to use it as an adjuvant therapy. The study was performed on 77 diabetic patients and divided into two phases: 29 compensated and 48 decompensated diabetic platelets were analyzed at recruitment (T0) and after in vitro RSV incubation (20 µg/ml) for 3 h at 37 °C (T1). 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 TMA-DPH and DPH were determined. In vitro RSV incubation counteracts oxidative damage associated with diabetes and its complications; it is able to improve platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it enhances antioxidant systems' functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels in both compensated and decompensated patients. Such platelet functionality enhancement suggests a new method of secondary prevention of complications associated with platelet dysfunction. Being free from one of the major risks associated with many antidiabetic agents, it can be assumed that RSV utilization in the diabetic diet may have a preventive and protective role in the progression of diabetic oxidative damage.

Leptin and paraoxonase activity in cord blood from obese mothers.

OBJECTIVE: Obesity and/or psychopathological disorders of parents represent risk factors for childhood obesity. The aim of the study was to investigate the link between obesity in pregnancy and oxidative stress. METHODS: Venous blood was collected from 37 women at the eighth month of gestation (19 obese and 28 normal weight). Cord blood was obtained at birth from newborns of obese mothers and controls. Cord blood and maternal blood was used to separate plasma to be used for the evaluation of leptin, oxidized LDL and paraoxonase (PON1) activity. RESULTS: Higher levels of leptin were observed both in maternal blood and cord blood of children of obese women compared to normal-weight women. The data also showed lower levels of PON1 activity in plasma of obese women and in the cord blood of their children. Furthermore, a positive correlation was established between levels of PON1 activity in maternal blood and cord blood, suggesting a relationship between PON1 in maternal plasma and fetal cord blood. CONCLUSIONS: Essential obesity in pregnancy is associated with hyperleptinemia. PON1 exerts an antioxidant role; therefore, our results demonstrated that obesity exposes to an increased susceptibility to oxidative damage in both mothers and newborns.

Biological effects of palytoxin-like compounds from Ostreopsis cf. ovata: a multibiomarkers approach with mussels Mytilus galloprovincialis.

Massive blooms of the harmful benthic dinoflagellate Ostreopsis cf. ovata are of growing environmental concern in the Mediterranean, having recently caused adverse effects on benthic invertebrates and also some intoxication episodes to humans. The toxicological potential of produced palytoxin-like compounds was investigated in the present study on a typical marine sentinel species, the mussel Mytilus galloprovincialis. Organisms were sampled during various phases of a O. cf. ovata bloom, in two differently impacted sites. The presence of the algal toxins was indirectly assessed in mussels tissues (mouse test and hemolysis neutralization assay), while biological and toxicological effects were evaluated through the measurement of osmoregulatory and neurotoxic alterations (Na(+)/K(+)-ATPase and acetylcholinesterase activities), oxidative stress responses (antioxidant defences and total oxyradical scavenging capacity), lipid peroxidation processes (level of malondialdehyde), peroxisomal proliferation, organelle dysfunctions (lysosomal membrane stability, accumulation of lipofuscin and neutral lipids), immunological impairment (granulocytes percentage). Obtained results demonstrated a significant accumulation of algal toxins in mussels exposed to O. cf. ovata. These organisms exhibited a marked inhibition of the Na(+)/K(+)-ATPase activity and alterations of immunological, lysosomal and neurotoxic responses. Markers of oxidative stress showed more limited variations suggesting that toxicity of the O. cf. ovata toxins is not primarily mediated by an over production of reactive oxygen species. This study provided preliminary results on the usefulness of a multi-biomarker approach to assess biological alterations and toxicological events associated to blooms of O. cf. ovata in marine organisms.

PP073. Gestational hypertension: A study on placental expression of endothelial and inducible nitric oxide synthase and no metabolism.

INTRODUCTION: Hypertension is one of the most common medical disorders in pregnancy and a major cause of maternal and perinatal morbidity and death. In primates adequate development of the embryo, and later of the fetus, depends on a successful hemomonochorial placentation. Nitric oxide (NO) a low molecular weight mediator, induces vasodilatation, inhibits platelet aggregation, and prevents the adhesion of platelets to endothelial cells. Till date, no data are available regarding gestational hypertension (GH) placenta and no metabolism and related enzyme expression and activity. OBJECTIVES: The present study aimed to evaluate eNOS and iNOS expression in the placentas of both normal and GH patients, by means of Real-Time quantitative PCR, measure placental nitric oxide and peroxynitrite levels in the same group of subjects, and correlate such findings with HELLP group already published. METHODS: Fifteen patients with gestational hypertension and thirty healthy pregnant controls comparable for maternal and gestational age were enrolled in the study. Placental tissue was taken immediately after delivery. eNOS and iNOS mRNA levels were evaluated Real-Time quantitative PCR, whereas nitric oxide and peroxynitrite production was measured by a commercially available kit. RESULTS: Placental eNOS and iNOS mRNA levels were significantly reduced in GH (2,02-fold reduction and 2,33-fold reduction, respectively) when compared to controls. Conversely, NO and ONOO(-) production were significantly higher in GH group compared to control group (31.56±4.15nmol NO/mg prot vs. 23.98±5.14nmol NO/mg prot and 68.49±8.57 arbitrary fluorescence units vs 17.31±2.25 arbitrary fluorescence units; p<0, 05). Such results were compared to HELLP group obtained in an already published study. CONCLUSION: As from results herein reported, we can hypothesize that complex mechanisms involving NO pathways cause a placental vasculature damage. However, it is not easy to understand if these changes could be interpreted as causes or consequences of this pathologic state.