56 research outputs found

    Role of the macrophage migration inhibitory factor in the pathophysiology of pre-eclampsia

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    Proinflammatory cytokines are produced in pregnancy in response to the invading pathogens and/or nonmicrobial causes such as damage-associated molecules and embryonic semi-allogenic antigens. While inflammation is essential for a successful pregnancy, an excessive inflammatory response is implicated in several pathologies including pre-eclampsia (PE). This review focuses on the proinflammatory cytokine macrophage migration inhibitory factor (MIF), a critical regulator of the innate immune response and a major player of processes allowing normal placental development. PE is a severe pregnancy-related syndrome characterized by exaggerated inflammatory response and generalized endothelial damage. In some cases, usually of early onset, it originates from a maldevelopment of the placenta, and is associated with intrauterine growth restriction (IUGR) (placental PE). In other cases, usually of late onset, pre-pregnancy maternal diseases represent risk factors for the development of the disease (maternal PE). Available data suggest that low MIF production in early pregnancy could contribute to the abnormal placentation. The resulting placental hypoxia in later pregnancy could produce high release of MIF in maternal serum typical of placental PE. More studies are needed to understand the role of MIF, if any, in maternal PE

    Intrapartum sonographic assessment of the fetal head flexion in protracted active phase of labor and association with labor outcome: a multicenter, prospective study

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    Background: To date, no research has focused on the sonographic quantification of the degree of flexion of the fetal head in relation to the labor outcome in women with protracted active phase of labor. Objective: This study aimed to assess the relationship between the transabdominal sonographic indices of fetal head flexion and the mode of delivery in women with protracted active phase of labor. Study Design: Prospective evaluation of women with protracted active phase of labor recruited across 3 tertiary maternity units. Eligible cases were submitted to transabdominal ultrasound for the evaluation of the fetal head position and flexion, which was measured by means of the occiput-spine angle in fetuses in nonocciput posterior position and by means of the chin-to-chest angle in fetuses in occiput posterior position. The occiput-spine angle and the chin-to-chest angle were compared between women who had vaginal delivery and those who had cesarean delivery. Cases where obstetrical intervention was performed solely based on suspected fetal distress were excluded. Results: A total of 129 women were included, of whom 43 (33.3%) had occiput posterior position. Spontaneous vaginal delivery, instrumental delivery, and cesarean delivery were recorded in 66 (51.2%), 17 (13.1%), and 46 (35.7%) cases, respectively. A wider occiput-spine angle was measured in women who had vaginal delivery compared with those submitted to cesarean delivery owing to labor dystocia (126±14 vs 115±24; P<.01). At the receiver operating characteristic curve, the area under the curve was 0.675 (95% confidence interval, 0.538–0.812; P<.01), and the optimal occiput-spine angle cutoff value discriminating between cases of vaginal delivery and those delivered by cesarean delivery was 109°. A narrower chin-to-chest angle was measured in cases who had vaginal delivery compared with those undergoing cesarean delivery (27±33 vs 56±28 degrees; P<.01). The area under the curve of the chin-to-chest angle in relation to the mode of delivery was 0.758 (95% confidence interval, 0.612–0.904; P<.01), and the optimal cutoff value discriminating between vaginal delivery and cesarean delivery was 33.0°. Conclusion: In women with protracted active phase of labor, the sonographic demonstration of fetal head deflexion in occiput posterior and in nonocciput posterior fetuses is associated with an increased incidence of cesarean delivery owing to labor dystocia. Such findings suggest that intrapartum ultrasound may contribute in the categorization of the etiology of labor dystocia

    Architecture, flexibility and performance of a special electron linac dedicated to Flash radiotherapy research: electronFlash with a triode gun of the centro pisano flash radiotherapy (CPFR)

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    The FLASH effect is a radiobiological phenomenon that has garnered considerable interest in the clinical field. Pre-clinical experimental studies have highlighted its potential to reduce side effects on healthy tissues while maintaining isoeffectiveness on tumor tissues, thus widening the therapeutic window and enhancing the effectiveness of radiotherapy. The FLASH effect is achieved through the administration of the complete therapeutic radiation dose within a brief time frame, shorter than 200 milliseconds, and, therefore, utilizing remarkably high average dose rates above at least 40 Gy/s. Despite its potential in radiotherapy, the radiobiological mechanisms governing this effect and its quantitative relationship with temporal parameters of the radiation beam, such as dose-rate, dose-per-pulse, and average dose-rate within the pulse, remain inadequately elucidated. A more profound comprehension of these underlying mechanisms is imperative to optimize the clinical application and translation of the FLASH effect into routine practice. Due to the aforementioned factors, the undertaking of quantitative radiobiological investigations becomes imperative, necessitating the utilization of sophisticated and adaptable apparatus capable of generating radiation beams with exceedingly high dose-rates and dose-per-pulse characteristics. This study presents a comprehensive account of the design and operational capabilities of a Linear Accelerator (LINAC) explicitly tailored for FLASH radiotherapy research purposes. Termed the “ElectronFlash” (EF) LINAC, this specialized system employs a low-energy configuration (7 and 9 MeV) and incorporates a triode gun. The EF LINAC is currently operational at the Centro Pisano FLASH Radiotherapy (CPFR) facility located in Pisa, Italy. Lastly, this study presents specific instances exemplifying the LINAC’s adaptability, enabling the execution of hitherto unprecedented experiments. By enabling independent variations of the temporal parameters of the radiation beam implicated in the FLASH effect, these experiments facilitate the acquisition of quantitative data concerning the effect’s dependence on these specific parameters. This novel approach hopefully contributes to a more comprehensive understanding of the FLASH effect, shedding light on its intricate radiobiological behavior and offering valuable insights for optimizing its clinical implementation

    Architecture, flexibility and performance of a special electron linac dedicated to Flash radiotherapy research: electronFlash with a triode gun of the centro pisano flash radiotherapy (CPFR)

    Get PDF
    The FLASH effect is a radiobiological phenomenon that has garnered considerable interest in the clinical field. Pre-clinical experimental studies have highlighted its potential to reduce side effects on healthy tissues while maintaining isoeffectiveness on tumor tissues, thus widening the therapeutic window and enhancing the effectiveness of radiotherapy. The FLASH effect is achieved through the administration of the complete therapeutic radiation dose within a brief time frame, shorter than 200 milliseconds, and, therefore, utilizing remarkably high average dose rates above at least 40 Gy/s. Despite its potential in radiotherapy, the radiobiological mechanisms governing this effect and its quantitative relationship with temporal parameters of the radiation beam, such as dose-rate, dose-per-pulse, and average dose-rate within the pulse, remain inadequately elucidated. A more profound comprehension of these underlying mechanisms is imperative to optimize the clinical application and translation of the FLASH effect into routine practice. Due to the aforementioned factors, the undertaking of quantitative radiobiological investigations becomes imperative, necessitating the utilization of sophisticated and adaptable apparatus capable of generating radiation beams with exceedingly high dose-rates and dose-per-pulse characteristics. This study presents a comprehensive account of the design and operational capabilities of a Linear Accelerator (LINAC) explicitly tailored for FLASH radiotherapy research purposes. Termed the “ElectronFlash” (EF) LINAC, this specialized system employs a low-energy configuration (7 and 9 MeV) and incorporates a triode gun. The EF LINAC is currently operational at the Centro Pisano FLASH Radiotherapy (CPFR) facility located in Pisa, Italy. Lastly, this study presents specific instances exemplifying the LINAC’s adaptability, enabling the execution of hitherto unprecedented experiments. By enabling independent variations of the temporal parameters of the radiation beam implicated in the FLASH effect, these experiments facilitate the acquisition of quantitative data concerning the effect’s dependence on these specific parameters. This novel approach hopefully contributes to a more comprehensive understanding of the FLASH effect, shedding light on its intricate radiobiological behavior and offering valuable insights for optimizing its clinical implementation

    Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

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    As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19

    Role of the macrophage migration inhibitory factor in the pathophysiology of pre-eclampsia

    Get PDF
    Proinflammatory cytokines are produced in pregnancy in response to the invading pathogens and/or nonmicrobial causes such as damage-associated molecules and embryonic semi-allogenic antigens. While inflammation is essential for a successful pregnancy, an excessive inflammatory response is implicated in several pathologies including pre-eclampsia (PE). This review focuses on the proinflammatory cytokine macrophage migration inhibitory factor (MIF), a critical regulator of the innate immune response and a major player of processes allowing normal placental development. PE is a severe pregnancy-related syndrome characterized by exaggerated inflammatory response and generalized endothelial damage. In some cases, usually of early onset, it originates from a maldevelopment of the placenta, and is associated with intrauterine growth restriction (IUGR) (placental PE). In other cases, usually of late onset, pre-pregnancy maternal diseases represent risk factors for the development of the disease (maternal PE). Available data suggest that low MIF production in early pregnancy could contribute to the abnormal placentation. The resulting placental hypoxia in later pregnancy could produce high release of MIF in maternal serum typical of placental PE. More studies are needed to understand the role of MIF, if any, in maternal PE

    Placental glucose transporters and response to bisphenol a in pregnancies from of normal and overweight mothers

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    Bisphenol A (BPA) is a synthetic phenol extensively used in the manufacture of polycar-bonate plastics and epoxy resins and a component of liquid and food storages. Among health disorders potentially attributed to BPA, the effects on metabolism have been especially studied. BPA represents a hazard in prenatal life because of its presence in tissues and fluids during pregnancy. Our recent study in rats fed with BPA showed a placental increase in glucose type 1 transporter (GLUT‐1), suggesting a higher uptake of glucose. However, the role of BPA on GLUT transporters in pregnant women with metabolic dysfunction has not yet been investigated. In this study, placental tissue from 26 overweight (OW) women and 32 age‐matched normal weight (NW) pregnant women were examined for expression of GLUT1 and GLUT4. Placental explants from OW and NW mothers were exposed to BPA 1 nM and 1 μM and tested for GLUTs expression. The data showed a different response of placental explants to BPA in GLUT1 expression with an increase in NW mothers and a decrease in OW ones. GLUT4 expression was lower in the explants from OW than NW mothers, while no difference was showed between OW and NW in placental biopsies for any of the transporters

    Ubidecarenone for the prevention of polymorphic light eruption and solar urticaria

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    Ubidecarenone (coenzyme Q) is a lipidsoluble quinone with anti-oxidative properties, which exerts a scavenger effect on oxygen free radicals. The effectiveness of ubidecarenone in modifying cutaneous reaction to light was evaluated in 7 patients with solar urticaria and 8 with polymorphic light eruption. The diagnosis was made for each patient by inducing lesions through phototests. Ubidecarenone was administered per os at a daily dose of 100 mg for 2 months. At the end of the treatment the phototests indicated the absence or reduction of skin photosensitivity in the majority of patients. These results suggest that ubidecarenone may be useful for the treatment of idiopathic photodermatitis
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