Glycosaminoglycans in the tongue of birds

We examined the literature to verify whether adaptations and modifications in the structure and glandular secretions of birds' tongues are related to habitat and can be ascribed to evolutionary processes. The data are discussed in relation to species taxonomy, following the Sibley and Ahlquist classification [C. G. Sibley and J. E. Alquist, Philogeny and Classification of Birds. A Study in Molecular Evolution (Yale University Press, New Haven, 1990)]. The following conclusions are drawn: gustatory papillae and taste buds are present in varying numbers in most species. The composition of gland secretions is also found to be variable. Proteic secretion is documented in Larus modestus, Sula variegata, Fulica atra only. Acid proteoglycans both with sulfomucins and carboxymucins, and also glycoproteins, are consistently found. Sialic and hyaluronic acids are found in many species. Our overview indicates that the presence or absence of gustatory papillae is related to adaptation processes that these structures undergo in response to environmental factors, and that the absence of front tongue glands can be ascribed to habitat and feeding habits. Referring to the Sibley and Ahlquist classification, proteins are present in the glandular secretion of less evolved species, whereas more evolved species exhibit a gradual decrease in proteins with the exception of hyaluronic acid, which is absent, and a progressive increase in glycoproteins and acid proteoglycans

Histological, histochemical and immunohistochemical study on the growing oocytes of the abyssal teleost Hoplostethus mediterraneus (V).

The oocytes of the abyssal Teleost, Hoplostethus mediterraneus were studied. Four stages of growth were observed and the oocytes of all the stages were surrounded by follicular cells and had several nucleoli in the nucleus. In the oocytes of the II degrees stage, vacuoles without contents, in oocytes of the III degrees stage several vacuoles with a basophilic contents and small yolk globules were identified. General and basic proteins, ribonucleoproteins, acid proteoglycans with -COOH groups were recognized in the cytoplasm, in the nucleoli of oocytes in the II degrees stage and in the vacuolar contents of oocytes in the III degrees stage. In the follicular cells, in the pellucid zone, in the yolk globules, from their beginning, glycoproteins were present. Positivity, for all lectins used, was revealed in the follicular cells and in the four stages of oocytes growth. alpha-D-glucose and alpha-D-mannose binding sites were in the pellucid zone and in the initial yolk globules. In the lather galactose and beta-N-acetyl glucosamine were present too. nNOS and VIP immunopositivity revealed at the periphery of the cytoplasm and at network of nerve fibres between oocytes, suggests NO is involved in a mechanism of regulation of the gametogenesis and of the spawning

Glycoconjugate histochemistry and nNOS immunolocalization in the mantle and foot epithelia of Tapes philippinarum (bivalve mollusc)

Glycosaminoglycans and NO synthase probably regulate mucous cell secretion in the skin of Tapes philippinarum. We have demonstrated the presence of "protein" cells, "glycogen" cells, "phenol" cells and five types of mucous cells, with different chemical composition of the mucus in the mantle epithelium of T. philippinarum. The foot epithelium contained "protein" cells and two types of mucous cells. Using biotinylated lectins, in the mantle and foot epithelia we have shown specific sites for the following oligosaccharides: α-D-glucose, α-D-mannose, α-L-fucose, α-D-1,3-N-acetyl-galactosamine and α-N-acetyl-glucosamine. nNOS immunoreactivity in the intraepithelial and intradermal cells and in the mucocytes suggested a regulatory role of NO in mucus secretion, as demonstrated also in other invertebrates

Histological, histochemical and immunohistochemical study on the growing oocytes of the abyssal teleost Hoplostethus mediterraneus (V).

The oocytes of the abyssal Teleost, Hoplostethus mediterraneus were studied. Four stages of growth were observed and the oocytes of all the stages were surrounded by follicular cells and had several nucleoli in the nucleus. In the oocytes of the II degrees stage, vacuoles without contents, in oocytes of the III degrees stage several vacuoles with a basophilic contents and small yolk globules were identified. General and basic proteins, ribonucleoproteins, acid proteoglycans with -COOH groups were recognized in the cytoplasm, in the nucleoli of oocytes in the II degrees stage and in the vacuolar contents of oocytes in the III degrees stage. In the follicular cells, in the pellucid zone, in the yolk globules, from their beginning, glycoproteins were present. Positivity, for all lectins used, was revealed in the follicular cells and in the four stages of oocytes growth. alpha-D-glucose and alpha-D-mannose binding sites were in the pellucid zone and in the initial yolk globules. In the lather galactose and beta-N-acetyl glucosamine were present too. nNOS and VIP immunopositivity revealed at the periphery of the cytoplasm and at network of nerve fibres between oocytes, suggests NO is involved in a mechanism of regulation of the gametogenesis and of the spawning

Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Abstract: Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries