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Nanomedicine provides various opportunities for addressing medical challenges associated with drug bioavailability, stability, and efficacy. In particular, oral nanoparticles (NPs) ...represent an alternative strategy to enhance the solubility and stability of active ingredients through the gastrointestinal tract. The nanocarriers could be used for both local and systemic targeting, enabling controlled release of encapsulated drugs. This approach allows more efficient therapies.
In this work, we aim to develop reliable oral solid dosage forms incorporating NPs produced by either one pot synthesis or continuous production, following protocols that yield highly consistent outcomes, promoting their technology transfer and clinical use.
Microfluidics technology was selected to allow an automated and highly productive synthetic approach suitable for the highly throughput production.
In particular, innovative systems, which combine advantage of NPs and solid dosage formulation, were designed, developed, and characterized demonstrating the possibility to obtaining oral administration. The resulting NPs were thus carried on oral dosage forms, i.e., pellets and minitablets. NPs resulted stable after dosage forms manufacturing, leading to confidence also on protection of encapsulated drugs. Indomethacin was used as a tracer to test biopharmaceutical behaviour.
Anti-inflammatories or cytotoxic chemotherapeutics could be vehiculated leading to a breakthrough in the treatment of severe diseases allowing the oral administration of these drugs. We believe that the advancement achieved with the results of our work paves the way for the progression of nanoproducts into clinical transition processes.
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in childhood. Skin barrier impairment exposes infants to food allergens, potentially causing sensitization followed by ...IgE-mediated food allergy. We describe the case of an infant with severe AD in whom several sensitizations to foods are detected, with consequently difficult weaning, and a history of anaphylaxis to cashew nut. Foods for which skin tests were negative were introduced into the infant's diet. Then, when AD control was managed, oral food challenges (OFCs) for foods to which the patient was sensitized, with the exception of cashew nut, were performed. The simultaneous presence of sensitization toward multiple foods made it difficult to introduce them using classic OFC. Therefore, it was decided to perform the low-dose, gradual controlled OFC. This led to an introduction of sensitized foods into the infant's diet, with the exception of cashew nut, avoiding allergic reactions. Absolute recommendations on how, when, and where to perform OFCs with allergenic food to which the child with AD is sensitized are lacking so far. In our opinion, OFCs and the subsequent ntroduction of allergenic foods should be individualized, evaluating some factors such as their social and nutritional importance, the patient's age and clinical phenotype (including the history of anaphylaxis), and the sensitization profile. There is agreement on the fact that the dietary approach in children with moderate-severe AD should no longer include a strict elimination diet. We believe that an early, gradual controlled introduction of all allergenics to identify the amount of food tolerated in the absence of reactions, even if low dose, may improve patients' and families' quality of life. However, even if discussing a vast relevant literature, the limitation of our work is that we describe the management of a single patient. Extensive and high-quality research is needed in this field to improve the available evidence in the area.
Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when highly emetogenic antineoplastic drugs are used. Uncontrolled emesis can profoundly impact on the ...patient's quality of life and ability to survive, by causing dehydration, electrolyte imbalance, malnutrition and treatment discontinuation.
The ABVD regimen (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) is considered the standard of care for first-line treatment of Hodgkin's Lymphoma. Among these drugs, dacarbazine and adriamycin are the most emetogenic, being classified as highly and moderately emetogenic chemotherapy, respectively.
NEPA is the first fixed antiemetic combination composed by the pharmacologically and clinically distinct 5HT3 receptor antagonist (5HT3-RA) palonosetron and the highly selective Neurokinin1/Substance P receptor antagonist (NK1-RA). A single dose of NEPA per chemotherapy cycle acts on the principal pathways involved in the mechanisms controlling nausea and vomiting in a synergistic way with an appropriate half-life to cover both the acute (0-24 hours from chemotherapy) and delayed (25-120 hours) phase.
In this open label multicenter study, chemo-naïve Hodgkin’s Lymphoma patients who were addressed to receive their first cycle of ABVD regimen (2 doses in 28 days, on days 1 and 15) were given a single administration of NEPA plus 4 mg dexamethasone. The primary endpoint was complete response (CR), defined as no emesis and no rescue medication during the overall phase (0-120 hours) on the first dose of the first ABVD cycle.
A total of 77 patients were evaluated. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. Indeed, the number of the complete responders for the overall phase among the first 70 consecutive patients was 66, which is greater than the pre-determined cut-off of 46, representing the minimum frequency of responders for which the treatment is considered effective. In addition to the primary efficacy endpoint, several additional endpoints were evaluated. The CR values were 93.5% for the acute phase, 81.8% for the delayed phase and 80.5% for the overall phase, while Complete Control (CR with no more than mild nausea) were achieved in the 93.5%of patients in the acute phase, 76.6% in the delayed phase and 75.3% in the overall phase (Figure 1A). Also, levels of no significant nausea (no more than mild nausea) were 94.6% for the acute phase, 83.1% for the delayed phase and 81.8% for the overall phase (Figure 1B).
This study demonstrated the efficacy of NEPA plus dexamethasone in preventing the nausea and vomiting induced by the highly emetogenic ABVD regimen.
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Abruzzese:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Di Renzo:BerGenBio ASA: Research Funding. Flenghi:takeda: Consultancy; Roche: Consultancy; janssen-cilag: Consultancy; teva: Consultancy; Servier Italia: Consultancy. Cantonetti:Vifor: Consultancy; Mundipharma: Consultancy; Roche: Consultancy; Takeda: Consultancy.
COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant ...organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented
gene-carrying Tn
transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs.
Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.
Siliceous sponges, one of the few animal groups involved in a biosilicification process, deposit hydrated silica in discrete skeletal elements called spicules. A multidisciplinary analysis of the ...structural features of the protein axial filaments inside the spicules of a number of marine sponges, belonging to two different classes (Demospongiae and Hexactinellida), is presented, together with a preliminary analysis of the biosilicification process. The study was carried out by a unique combination of techniques: fiber diffraction using synchrotron radiation, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetric (DSC), Fourier transform infrared spectroscopy (FTIR), and molecular modeling. From a phylogenetic point of view, the main result is the structural difference between the dimension and packing of the protein units in the spicule filaments of the Demospongiae and the Hexactinellida species. Models of the protein organization in the spicule axial filaments, consistent with the various experimental evidences, are given. The three different species of demosponges analyzed have similar general structural features, but they differ in the degree of order. The structural information on the spicule axial filaments can help shed some light on the still unknown molecular mechanisms controlling biosilicification.
Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and the ...ER-stress-induced oxidoreductase ERO1A. SEPN1 and ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved in the redox regulation of proteins. ERO1A depletion in SEPN1 knockout cells restores ER redox, re-equilibrates short-range MAMs, and rescues mitochondrial bioenergetics. ERO1A knockout in a mouse background of SEPN1 loss blunts ER stress and improves multiple MAM functions, including Ca2+ levels and bioenergetics, thus reversing diaphragmatic weakness. The treatment of SEPN1 knockout mice with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) mirrors the results of ERO1A loss. Importantly, muscle biopsies from patients with SEPN1-RM exhibit ERO1A overexpression, and TUDCA-treated SEPN1-RM patient-derived primary myoblasts show improvement in bioenergetics. These findings point to ERO1A as a biomarker and a viable target for intervention and to TUDCA as a pharmacological treatment for SEPN1-RM.
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•SEPN1 interacts with the endoplasmic-reticulum-stress-induced oxidoreductase ERO1A•Upregulation of ERO1A is a hallmark of the SEPN1-RM preclinical models•Targeting ERO1A improves the muscle disease phenotype of SEPN1-RM•TUDCA, a pan ER stress inhibitor, is an effective pharmacological strategy for SEPN1-RM
SEPN1-related myopathy (SEPN1-RM) is a congenital muscle disorder with no approved pharmacological treatment. Germani et al. show an interaction between SEPN1 and ERO1A and that targeting ERO1A improves the muscle phenotype of SEPN1-RM. Furthermore, they find that TUDCA, an FDA-approved drug, is an effective pharmacological strategy for SEPN1-RM.
Aclimatação ao frio e dano por geada em canola Dalmago, Genei Antonio; Cunha, Gilberto Rocca da; Santi, Anderson ...
Pesquisa Agropecuária Brasileira,
09/2010, Letnik:
45, Številka:
9
Journal Article
Recenzirano
Odprti dostop
O objetivo deste trabalho foi avaliar a influência da aclimatação ao frio sobre o dano causado pela geada em diferentes estádios fenológicos de genótipos de canola. Foram realizados cinco ...experimentos em ambiente controlado, em 2006, 2007 e 2008. Os fatores avaliados foram: genótipos, aclimatação (com; sem), intensidades de geada, estádios de desenvolvimento de plantas, regimes de aclimatação e regimes de geada. As variáveis avaliadas foram: queima de folhas, massa de matéria seca, estatura de plantas, duração de subperíodo, componentes de rendimento e rendimento de grãos. A aclimatação ao frio, antes da geada, resultou em menor queima de folhas e maior massa de matéria seca, em comparação a plantas não aclimatadas. As geadas foram prejudiciais a partir de -6°C no início do ciclo de desenvolvimento, principalmente em plantas não aclimatadas, e a partir de -4ºC na floração, com redução do número de síliquas e do número de grãos por síliqua. A aclimatação após as geadas não contribuiu para a tolerância da canola a esse evento. Geadas consecutivas não acarretaram maior prejuízo à canola. A aclimatação de plantas de canola antes da geada reduz os danos, principalmente quando a geada ocorre no início do desenvolvimento das plantas.
Aclimatação ao frio e dano por geada em canola Dalmago, Genei Antonio; Cunha, Gilberto Rocca da; Santi, Anderson ...
Pesquisa agropecuaria brasileira,
09/2010, Letnik:
45, Številka:
9
Journal Article
Recenzirano
O objetivo deste trabalho foi avaliar a influência da aclimatação ao frio sobre o dano causado pela geada em diferentes estádios fenológicos de genótipos de canola. Foram realizados cinco ...experimentos em ambiente controlado, em 2006, 2007 e 2008. Os fatores avaliados foram: genótipos, aclimatação (com; sem), intensidades de geada, estádios de desenvolvimento de plantas, regimes de aclimatação e regimes de geada. As variáveis avaliadas foram: queima de folhas, massa de matéria seca, estatura de plantas, duração de subperíodo, componentes de rendimento e rendimento de grãos. A aclimatação ao frio, antes da geada, resultou em menor queima de folhas e maior massa de matéria seca, em comparação a plantas não aclimatadas. As geadas foram prejudiciais a partir de -6°C no início do ciclo de desenvolvimento, principalmente em plantas não aclimatadas, e a partir de -4ºC na floração, com redução do número de síliquas e do número de grãos por síliqua. A aclimatação após as geadas não contribuiu para a tolerância da canola a esse evento. Geadas consecutivas não acarretaram maior prejuízo à canola. A aclimatação de plantas de canola antes da geada reduz os danos, principalmente quando a geada ocorre no início do desenvolvimento das plantas.
The objective of this work was to evaluate the influence of cold acclimatization on frost damage at different phenological stages of canola genotypes. Five experiments were carried out under controlled conditions, in 2006, 2007, and 2008. The evaluated factors were: genotypes, acclimatization (with; without), frost gradient, plant developmental stages, acclimatization regimes and frost regimes. The evaluated variables were: leaf scorching symptoms, dry weight, plant height, length of subperiod, yield components and grain yield. The acclimatization before frost resulted in lesser leaf scorching symptoms and higher dry matter in comparison to plants not acclimated. Frosts were harmful from -6°C in early plant development stage, mainly in nonacclimated plants, and from -4ºC at flowering, reducing the number of pods and the number of grains per pod. Acclimatization after frost did not contribute to the tolerance of canola to frost. Consecutive frosts caused no greater impairment to canola. The canola acclimatization before frost reduces damage caused by it, mainly when the frost occur in the initial plant development stages.
O objetivo deste trabalho foi avaliar a influência da aclimatação ao frio sobre o dano causado pela geada em diferentes estádios fenológicos de genótipos de canola. Foram realizados cinco ...experimentos em ambiente controlado, em 2006, 2007 e 2008. Os fatores avaliados foram: genótipos, aclimatação (com; sem), intensidades de geada, estádios de desenvolvimento de plantas, regimes de aclimatação e regimes de geada. As variáveis avaliadas foram: queima de folhas, massa de matéria seca, estatura de plantas, duração de subperíodo, componentes de rendimento e rendimento de grãos. A aclimatação ao frio, antes da geada, resultou em menor queima de folhas e maior massa de matéria seca, em comparação a plantas não aclimatadas. As geadas foram prejudiciais a partir de -6°C no início do ciclo de desenvolvimento, principalmente em plantas não aclimatadas, e a partir de -4ºC na floração, com redução do número de síliquas e do número de grãos por síliqua. A aclimatação após as geadas não contribuiu para a tolerância da canola a esse evento. Geadas consecutivas não acarretaram maior prejuízo à canola. A aclimatação de plantas de canola antes da geada reduz os danos, principalmente quando a geada ocorre no início do desenvolvimento das plantas.The objective of this work was to evaluate the influence of cold acclimatization on frost damage at different phenological stages of canola genotypes. Five experiments were carried out under controlled conditions, in 2006, 2007, and 2008. The evaluated factors were: genotypes, acclimatization (with; without), frost gradient, plant developmental stages, acclimatization regimes and frost regimes. The evaluated variables were: leaf scorching symptoms, dry weight, plant height, length of subperiod, yield components and grain yield. The acclimatization before frost resulted in lesser leaf scorching symptoms and higher dry matter in comparison to plants not acclimated. Frosts were harmful from -6°C in early plant development stage, mainly in nonacclimated plants, and from -4ºC at flowering, reducing the number of pods and the number of grains per pod. Acclimatization after frost did not contribute to the tolerance of canola to frost. Consecutive frosts caused no greater impairment to canola. The canola acclimatization before frost reduces damage caused by it, mainly when the frost occur in the initial plant development stages.
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