Rapidly-Disintegrating Laminar Extrudates: Preliminary Experiments upon an Age Appropriate Pediatric Formulation

The aim of the present investigation is to produce rapidly disintegrating laminar extrudates for delivering ibuprofen in the mouth of paediatric patients. This laminar shape is particularly convenient for drug delivering in the mouth and can be easily cut in cut in different sizes allowing for a convenient adjustment of the drug dose depending on the age of the patient. Due to the fact that in paediatric formulations, the selection of the excipients is always a challenging issue and the reduction of their amount is always highly desirable, in this study to select the most appropriate composition to achieve a rapid disintegration and simultaneously permit a high amount of ibuprofen in the system, an experimental design for mixtures was employed and the disintegration time in simulated saliva was used as experimental response. In addition, after solid state analyses to check possible insurgence of drug-excipients interactions, laminar extrudates were characterised in terms of mechanical properties and in vitro dissolution performances. Extrudates with the desired uniform laminar shape, constant thickness (2 mm) and a very high content of drug (82% wt) were produced. These products exhibited a short disintegration time. The dose for a patient of 6-12 years corresponded to a length of extrudate between 1-1.5 cm, perfectly compatible with a formulation orodispersible thin laminar extrudate intended for a paediatric patient (Figure 1)

From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form

Competitive Mechanochemical Solvate Formation of Theophylline in the Presence of Miscible Liquid Mixtures

In this study, we investigated the mechanochemical competitive solvate formation of polymorphic Form II of theophylline in the presence of two solvate/hydrate-forming miscible liquids, namely, water and 2-pyrrolidone. It is known that theophylline transforms into a monohydrate in the presence of water, while 2-pyrrolidone gives a monosolvate or a sesquisolvate, depending on the experimental conditions. Different theophylline-to-liquid molar ratios and several water:2-pyrrolidone mixtures were used to understand the competitive formation and/or transformation between these solvates. Interconversion studies between hydrate/monosolvate/sesquisolvate forms were also conducted. The obtained results suggest that water:2-pyrrolidone mixtures have a detrimental effect on the formation of multicomponent phases, as they dramatically reduce the efficiency of incorporation of both liquids in the crystal. In fact, all milling experiments performed in the presence of water:2-pyrrolidone mixtures suggested that a higher stoichiometric ratio is needed to obtain a pure form of a specific solvate. Importantly, additional competitive milling experiments revealed a preferential inclusion of 2-pyrrolidone over water. Based on several experimental datasets performed, we conclude that the propensity of solvate formation in the presence of liquid mixtures is a consequence of a complex interplaying of physicochemical and kinetic factors

Subtle reproductive impairment through nitric oxide-mediated mechanisms in sea urchins from an area affected by harmful algal blooms

The health of the sea urchin Paracentrotus lividus, a key species in the Mediterranean Sea, is menaced by several pressures in coastal environments. Here, we aimed at assessing the reproductive ability of apparently healthy P. lividus population in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata. Wide-ranging analyses were performed in animals collected prior to and during the bloom, as well as at several times thereafter, during the reproductive season. Adults showed a low fertilization rate, along with high nitric oxide (NO) levels in the gonads and the nitration of the major yolk protein toposome, which is an important player in sea urchin development. Serious developmental anomalies were observed in the progeny, which persist several months after the bloom. NO levels were high in the different developmental stages, which also showed variations in the transcription of several genes that were found to be directly or indirectly modulated by NO. These results highlight subtle but important reproductive flaws transmitted from the female gonads to the offspring with the NO involvement. Despite a recovery along time after the bloom, insidious damages can be envisaged in the local sea urchin population, with possible reverberation on the whole benthic system

Novel heterococcolithophores, holococcolithophores and life cycle combinations from the families Syracosphaeraceae and Papposphaeraceae and the genus Florisphaera

Abstract. Coccolithophores are a diverse group of calcifying phytoplankton, which are responsible for a large part of the modern oceanic carbonate production. Here, we describe novel or poorly known coccolithophores and novel life cycle combination coccospheres detected in samples collected either in the Gulf of Aqaba in the northern Red Sea or in the Gulf of Naples in the western Mediterranean. These include Syracosphaera winteri, for which detached coccoliths have previously been recorded but both a formal description and taxonomic affiliation were lacking, and five undescribed sets of combination cells linking HET and HOL forms for S. pulchra, S. mediterranea, S. azureaplaneta, S. lamina and S. orbicula. We also propose the replacement name S. kareniae for the fossil species Deutschlandia gaarderae. We describe a new species of the genus Ophiaster, O. macrospinus, displaying a unique morphological and ecological distribution as well as putative combination cells of two variants of the deep-dwelling Florisphaera profunda, which provide new insights on the affiliation of this genus within the Calcihaptophycideae. Additionally, in the family Papposphaeraceae we detected a new species, Pappomonas vexillata, and combination cells of Picarola margalefi and of a species resembling Papposphaera arctica. Finally, we detected three novel, unpaired holococcolithophore forms (Calyptrosphaera lluisae, Calicasphaera bipora and one form designated as Holococcolithophore A). Overall, this set of novel observations and ensuing discussions provide further insights into the diversity, evolution and life cycle complexity of coccolithophores in the oceans

P216 Comparative Assessment C-reactive Protein Between a Point-of-Care Testing and Current Standard of Care (Immunonephelometric testing)

Abstract Background C-reactive protein (CRP) is widely used as a biomarker of inflammatory disease activity in hospitalized and non-hospitalized patients. In particular, CRP is commonly used in patients suspected to have an inflammatory bowel disease (IBD) or with a confirmed diagnosis of IBD diagnosis in order to drive the diagnostic approach, to monitor disease activity and to guide therapeutic adjustments. However, standard laboratory CRP testing (Immunonephelometric assays) present some drawbacks, including a turnaround time of 1–2 hours, and the need of specialized equipment, offices and laboratory personnel. Because of that, point-of care testing (POCT) was recently developed in order to provide results within 2 minutes from blood collection, enabling a rapid response to clinical condition. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) using capillary whole blood and the comparative Immunonephelometric assay using serum samples. Methods From October to November 2020, consecutive patients hospitalized at Gastroenterology Unit, Padua University Hospital, aged > 18 years and with clinical evidence of active inflammatory disease or infection, who underwent to a standard of care CRP test (Dimension Vista – Siemens Healthineers) were included in the study (range 2.9–340 g/L). Within 1 hour from blood collection, in each patient, CRP quantitation from capillary whole blood collected by finger stick was performed using the ProciseDx CRP assay, with reportable range between 3.6–100 g/L. A Deming regression test was used to identify the correlation between the two methods. Results Eighty-three patients were enrolled (62.5% males with mean age ± SD: 60±18). The most common indications for hospitalisation were liver disease (34.9%), pancreatic disturbance (27.7%) and suspicious or recurrence of IBD (16.7%). ProciseDx POCT with finger prick samples required a turnaround time of 2±0.2 minutes, whereas serum samples analyzed in clinical laboratory with the reference method required a turnaround time of about 180±15 minutes (p<0.001). Overall, the correlation between the two tests was high (R squared of 0.899 (95% CI 0.916–0.968)). In particular, the correlation between the methods was even higher with CRP values between 0–100 g/L with R squared of 0.961 (95% CI 0.958–0.986). Conclusion The ProciseDx POCT allows a more rapid and comparable accuracy of CRP assessment in hospitalized patients as compared to the standard laboratory measurement. Moreover, the ProciseDx POCT does not require specialised personnel to be performed. The use of ProciseDx POCT may improve and accelerate the decision-making approach, further reducing the resources required for CRP assessment

Low incidence but poor prognosis of complicated coeliac disease: A retrospective multicentre study.

Abstract BACKGROUND: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. METHODS: Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. RESULTS: Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. CONCLUSIONS: Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality

Invited review: Bovine colostrum, a promising ingredient for humans and animals—Properties, processing technologies, and uses

Mammalian colostrum, known as “liquid gold,” is considered a valuable source of essential nutrients, growth factors, probiotics, prebiotics, antibodies, and other bioactive compounds. Precisely for this reason, bovine colostrum (BC) is an emerging ingredient for the feed, food, and pharmaceutical industries, being nowadays commercially available in a variety of forms in several countries. Moreover, quite a large number of functional foods and supplements for athletes, human medicines, pet nutrition plans, and complementary feed for some livestock categories, such as piglets and calves, contain BC. The amount of BC yielded by a cow after calving represents approximately 0.5% of the yearly output in dairy breeds. For its nutritional properties and low availability, BC is characterized by a greater market value and an increasing demand compared with other by-products of the dairy sector. However, information regarding the market size of BC for the food and pharmaceutical industries, as well as future developments and perspectives, is scarcely available in the scientific literature. This lack can be attributed to industrial secrecy as well as to the relatively small scale of the BC business when compared with other dairy products, which makes the BC market limited, specific, and intended for a restricted audience. From a legal perspective, regulations assign BC to the large family of milk-derived powders; thus, collecting specific production data, as well as import-export trend information, is not straightforward and can result in unprecise estimates. Given that the interest in BC is increasing in different fields, it is important to have an overview of the production steps and of pros and cons of this emerging ingredient. The present narrative review discloses why BC has started to be considered a product rather than a by-product of the dairy industry. Moreover, the present document aims to summarize the existing methodologies used to assess BC quality in terms of immunoglobulin concentration, the different applications of BC in the industry, and the BC processing technologies. Finally, a panoramic view of the current international market is provided for the first time for this dairy product

Strengthening Europe's Capability in Biological Ocean Observations

This publication is primarily aimed at stakeholders involved in ocean observing, spanning diverse roles from commissioning, managing, funding and coordinating, to developing, implementing, or advising on, ocean observation programmes. Such programmes will have strategic and policy drivers but their main purpose may vary from predominantly researchdriven scientific purposes to environmental monitoring for providing data and reporting to legally-binding regulations or directives. The main focus is on European capabilities but set in a global context with the various actors spanning a variety of geographical scales from national to regional and European. Key stakeholder organizations include environmental or other agencies; marine research institutions, their researchers and operators; international and regional ocean observing initiatives and programmes; national, regional and European policy makers and their advisors; national stations for observations; etc.). It will also be of interest to the wider marine and maritime research and policy community. The main aim of the publication is to increase the relevance of current (and future) European biological ocean observation capacity to strengthen global efforts towards our understanding of the ocean and enhance marine biodiversity conservation, for maintaining a healthy ocean for healthy societies. This document explains why biological ocean observations are needed to assess progress against national and international conservation targets, the Sustainable Development Goals (SDGs), the Blue Growth agenda and to contribute to key EU directives including the Marine Strategy Framework Directive (MSFD). To achieve this, the publication highlights the need of biological ocean observations to reflect clearly defined hypotheses about potential causes of change, including the combined impacts of local and global drivers, and to support the management of our impacts on the ocean. Additionally, it calls for flexible biological ocean observing programmes to capture the relevant drivers operating at multiple spatial scales, by networking and integration of ongoing monitoring programmes, methodological standardization and appropriate policies of data integration and dissemination. It then presents key variables, elements and information products to inform on the status and trends of marine biodiversity

Biotic and environmental stress induces nitration and changes in structure and function of the sea urchin major yolk protein toposome

The major yolk protein toposome plays crucial roles during gametogenesis and development of sea urchins. We previously found that nitration of toposome increases in the gonads of a Paracentrotus lividus population living in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata, compared to control populations. This modification is associated with ovatoxin accumulation, high levels of nitric oxide in the gonads, and a remarkable impairment of progeny development. However, nothing is known about the environmental-mediated-regulation of the structure and biological function of toposome. Here, we characterize through wide-ranging biochemical and structural analyses the nitrated toposome of sea urchins exposed to the bloom, and subsequently detoxified. The increased number of nitrated tyrosines in toposome of sea urchins collected during algal bloom induced structural changes and improvement of the Ca2+-binding affinity of the protein. After 3 months' detoxification, ovatoxin was undetectable, and the number of nitric oxide-modified tyrosines was reduced. However, the nitration of specific residues was irreversible and occurred also in embryos treated with metals, used as a proxy of environmental pollutants. The structural and functional changes of toposome caused by nitration under adverse environmental conditions may be related to the defective development of sea urchins' progeny