Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

INTRODUCTION: The purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5). MATERIALS AND METHODS: Patients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO2 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 upslope) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated. RESULTS: The mean +/- standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 +/- 6.6 and 28.6 +/- 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 +/- 1.3 vs. 1.9 +/- 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 +/- 2.2 vs. 12.2 +/- 3.2; P < 0.05). There were no differences between groups in StO2 baseline. StO2 downslope in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 +/- 11.8 vs. -8.1 +/- 2.4%/minute) was significantly steeper than in the control group. StO2 upslope increased and was higher than in the control group at T1c, T1d and T2 (101.1 +/- 62.1 vs. 54.5 +/- 23.8%/minute) (P < 0.05). CONCLUSIONS: Treatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 downslope). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patient

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant

Prevention of Congenital Cytomegalovirus Infection with Vaccines: State of the Art

Cytomegalovirus (CMV) is the most common cause of congenital infection and non-genetic sensorineural hearing loss in childhood. Up to 2% of neonates, with the highest percentages found in developing countries, are congenitally infected with CMV. At birth, most of these infants are asymptomatic. However, approximately 10% have signs and symptoms of the disease, and 40–60% of symptomatic neonates will later develop permanent neurologic sequelae. To reduce congenital CMV (cCMV) infection, a vaccine able to prevent primary infection is essential. In this narrative review, actual ongoing research about the development of a CMV vaccine is discussed. The progressive increase in knowledge on the ways in which the host’s immune system and CMV relate has made it possible to clarify that the development of a vaccine that is certainly capable of reducing the risk of cCMV infection, and preventing both primary and nonprimary infections is extremely difficult. Many of the ways in which the virus evades the immune system and causes cCMV infection are not yet fully understood, especially in cases of nonprimary infection. Moreover, the schedule that should be recommended and that subjects must be vaccinated to obtain the greatest effect have not been precisely defined. Further studies are needed before the problem of cCMV infection and its related challenges can be totally solved

Olive oil supplemented with Coenzyme Q(10): effect on plasma and lipoprotein oxidative status

Olive oil consumption is associated with protective cardiovascular properties, including some beneficial modifications in lipoprotein profile and composition. Coenzyme Q(10) (CoQ(10)) exerts a protective effect on plasma lipoproteins. Aim of the study was to investigate whether extra virgin (EV) olive oil enriched with CoQ(10) affects CoQ(10) levels and oxidative status in plasma and in isolated lipoproteins. Twelve subjects were administered 20 mL olive oil per day for 2 weeks, followed by 2 weeks of olive oil enriched with 20 mg and 2 more weeks with 40 mg of CoQ(10). Plasma and isolated lipoproteins were collected in each phase of the study and subsequently analyzed to assess lipid profile, CoQ10 levels, ORAC assay, resistance of lipoproteins to peroxidation and paroxonase 1 activity. Plasma CoQ(10) levels significantly increased with the 20 mg (+73%) and 40 mg dose (+170%), while the percentage of oxidized CoQ(10) decreased. A significant inverse correlation was found in plasma between percentage of oxidized CoQ(10) and total antioxidant capacity. A lower susceptibility of LDL to peroxidation was also found. Finally, a positive correlation was observed between concentration of CoQ(10) in HDL and paraoxonase-1 activity. EV olive oil enriched with both doses of CoQ(10) significantly affects its bioavailability and plasma redox status. These changes are associated with a decreased susceptibility of plasma lipoproteins to peroxidation associated with a chain-breaking antioxidant activity of the formulation

NAD(P)H:quinone oxidoreductase (NQO1) loss of function in Burkitt's lymphoma cell lines.

Abstract: Two-electron reduction of quinones catalyzed by NAD(P)H:quinone oxidoreductase (NQO1) protects cells against oxidative stress and toxic quinones. In fact, low level of NQO1 activity is often associated with increased risk of developing different types of tumours and with toxic effects linked to environmental quinones. In a previous report we analyzed the relationship between the oxidative stress induced by UV radiation and CoQ(10) content in Burkitt's lymphoma cell lines compared to HL-60. The basal content of CoQ(10) in Raji cells was slightly higher compared to HL-60. Moreover, after irradiation or ubiquinone supplementation in the medium, reduced CoQ(10) levels were higher in Raji and Daudi cells compared to HL-60. In the present work, in order to inquire if NQO1 plays a role in the CoQ reducing capacity observed in the lymphoblastoid cell lines, we analyzed the transcription and translation products of this gene in Raji and Daudi cells, compared to cell lines possessing low and high NQO1 activity. The amount of transcripts of this gene in lymphoblastoid cells was comparable to that observed in HL-60 cells (low activity), as well as the level of two alternatively spliced mRNAs; one of which is described for the first time in this work. From the genotype analysis of polymorphisms C609T and C465T we observed that HL-60, Raji and Daudi cells were all heterozygous. Furthermore, NQO1 enzyme activity and protein synthesis in the cytosol of Raji and Daudi cells were undetectable. Therefore in Burkitt's lymphoma cell lines the NQO1 gene is not efficiently translated and this effect is not related to (C609T) polymorphism. Further studies will be necessary to find the enzyme responsible for CoQ,() reducing activity observed in lymphoma cell lines. On the other hand, this result suggests a careful re-evaluation of data concerning loss of NQO1 activity and polymorphisms in tumour cells

Olive oil supplemented with Coenzyme Q10: Effect on plasma and lipoprotein oxidative status

Olive oil consumption is associated with protective cardiovascular properties, including some beneficial modifications in lipoprotein profile and composition. Coenzyme Q(10) (CoQ(10)) exerts a protective effect on plasma lipoproteins. Aim of the study was to investigate whether extra virgin (EV) olive oil enriched with CoQ(10) affects CoQ(10) levels and oxidative status in plasma and in isolated lipoproteins. Twelve subjects were administered 20 mL olive oil per day for 2 weeks, followed by 2 weeks of olive oil enriched with 20 mg and 2 more weeks with 40 mg of CoQ(10). Plasma and isolated lipoproteins were collected in each phase of the study and subsequently analyzed to assess lipid profile, CoQ10 levels, ORAC assay, resistance of lipoproteins to peroxidation and paroxonase 1 activity. Plasma CoQ(10) levels significantly increased with the 20 mg (+73%) and 40 mg dose (+170%), while the percentage of oxidized CoQ(10) decreased. A significant inverse correlation was found in plasma between percentage of oxidized CoQ(10) and total antioxidant capacity. A lower susceptibility of LDL to peroxidation was also found. Finally, a positive correlation was observed between concentration of CoQ(10) in HDL and paraoxonase-1 activity. EV olive oil enriched with both doses of CoQ(10) significantly affects its bioavailability and plasma redox status. These changes are associated with a decreased susceptibility of plasma lipoproteins to peroxidation associated with a chain-breaking antioxidant activity of the formulatio

Silence of the Lambs: The Immunological and Molecular Mechanisms of COVID-19 in Children in Comparison with Adults

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19

An unusual case of primary intrascrotal lipoma

In daily clinical practice, intrascrotal lesion are commonly detected, both by clinical examination either by ultrasound scan. While 95% of testicular lesions are malignant, most paratesticular lesions are benign. Among these, intrascrotal lipomas must be take into account in differential diagnosis. When they originate from scrotal wall, they named “primary scrotal lipoma”. We describe a case of a primary intrascrotal lipoma diagnosed after surgical excision in a young man presented at our Urological Department complaining a painful left scrotal mass

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n = 89) and from MS patients (n = 24) in the early stage disability (EDSS<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (P <0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (P<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS