35 research outputs found
Nanopharmaceuticals for eye administration: sterilization, depyrogenation and clinical applications
As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. The design of an efficient ocular drug delivery system still remains a challenge. Although nanotechnology may offer the ability to detect and treat eye diseases, successful treatment approaches are still in demand. The growing interest in nanopharmaceuticals offers the opportunity to improve ophthalmic treatments. Besides their size, which needs to be critically monitored, nanopharmaceuticals for ophthalmic applications have to be produced under sterilized conditions. In this work, we have revised the different sterilization and depyrogenation methods for ophthalmic nanopharmaceuticals with their merits and drawbacks. The paper also describes clinical sterilization of drugs and the outcomes of inappropriate practices, while recent applications of nanopharmaceuticals for ocular drug delivery are also addressed.The authors acknowledge the sponsorship received from the Portuguese Science and Technology
Foundation, Ministry of Science and Education (FCT/MEC) through national funds, co-financed by FEDER, under the Partnership Agreement PT2020 for the project UIDB/04469/2020 (strategic fund) granted to EBS, the National Council for Scientific and Technological Development (CNPq), Brazil, for the project 425271/2016-1 granted to M.V.C., and the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ămparo Ă Pesquisa do Estado de Sergipe (FAPITEC) (88887.159533/2017-00), Conselho Nacional de Desenvolvimento CientĂfico e TecnolĂłgico (CNPq301964/2019-0 Chamada 06/2019, and Chamada CNPq nÂș 01/2019), granted to P.S.info:eu-repo/semantics/publishedVersio
Adhesive protein-mediated crosstalk between <i>Candida albicans</i> and <i>Porphyromonas gingivalis</i> in dual species biofilm protects the anaerobic bacterium in unfavorable oxic environment
Abstract The oral cavity contains different types of microbial species that colonize human host via extensive cell-to-cell interactions and biofilm formation. Candida albicans âa yeast-like fungus that inhabits mucosal surfacesâis also a significant colonizer of subgingival sites in patients with chronic periodontitis. It is notable however that one of the main infectious agents that causes periodontal disease is an anaerobic bacteriumâ Porphyromonas gingivalis. In our study, we evaluated the different strategies of both pathogens in the mutual colonization of an artificial surface and confirmed that a protective environment existed for P. gingivalis within developed fungal biofilm formed under oxic conditions where fungal cells grow mainly in their filamentous form i.e. hyphae. A direct physical contact between fungi and P. gingivalis was initiated via a modulation of gene expression for the major fungal cell surface adhesin Als3 and the aspartic proteases Sap6 and Sap9. Proteomic identification of the fungal surfaceome suggested also an involvement of the Mp65 adhesin and a âmoonlightingâ protein, enolase, as partners for the interaction with P. gingivalis. Using mutant strains of these bacteria that are defective in the production of the gingipainsâthe proteolytic enzymes that also harbor hemagglutinin domainsâsignificant roles of these proteins in the formation of bacteria-protecting biofilm were clearly demonstrated
Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)âPolish compassionate use experience
Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (Nâ=â23), non-Hodgkinâs lymphoma (Nâ=â20), or Hodgkinâs lymphoma (Nâ=â18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/ÎŒL (range of 0â121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0â4) aphereses were performed. A minimum of 2.0âĂâ106 CD34+ cells per kilogram of the patientâs body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67âĂâ106 CD34+ cells/kg b.w. (0â8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkinâs lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers
Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study
BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12âgâdl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (â„week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] gâdl-1 for neonates in week 1, 9.6 [7.7 to 10.4] gâdl-1 in week 2 and 8.0 [7.3 to 9.0] gâdl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] mlâkg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] gâdl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
The Arctic soil bacterial communities in the vicinity of a little auk colony
Due to deposition of birdsâ guano, eggshells or feathers, the vicinity of a large seabirdsâ breeding colony is expected to have a substantial impact on the soilâs physicochemical features as well as on diversity of vegetation and the soil invertebrates. Consequently, due to changing physicochemical features the structure of bacterial communities might fluctuate in different soil environments. The aim of this study was to investigate the bacterial assemblages in the Arctic soil within the area of a birdsâ colony and in a control sample from a topographically similar location but situated away from the colonyâs impact area. A high number of OTUs found in both areas indicates a highly complex microbial populations structure. The most abundant phyla in both of the tested samples were: Proteobacteria, Acidobacteria, Actinobacteria and Chloroflexi, with different proportions in the total share. Despite differences in the physicochemical soil characteristics, the soil microbial community structures at the phylum level were similar to some extent in the two samples. The only share that was significantly higher in the control area when compared to the sample obtained within the birdsâ colony, belonged to the Actinobacteria phylum. Moreover, when analyzing the class level for each phylum, several differences between the samples were observed. Furthermore, lower proportions of Proteobacteria and Acidobacteria were observed in the soil sample under the influence of the birdâs colony, which most probably could be linked to higher nitrogen concentrations in that sample
Thermal stability of the elastomeric anti-trauma pad
The elastomeric anti-trauma pad (EA-TP) based on shear thickening fluid (STF) has been developed. Dynamic oscillatory shear experiment was conducted at constant strain amplitude of 5%. STF composed of 25% of volume fraction of 7 nm Fumed Silica, dispersed in polypropylene glycol with molar mass 400 gmolâ1 shows elastic properties in entire investigated range of the frequency. Ballistic tests of EA-TP with 7.62 mm Ă 39 mm PS bullets were performed according to the PN-V-87000:2011 standard. The studies revealed about 60% reduction of the average backface signature depth (BSD) for the EA-TP, when compared to the nowadays commonly used soft insert. The ATR-FTIR analysis confirmed slight impact of the elevated temperature and air (oxygen) on the chemical degradation of the EA-TP surface. The UV-VIS spectroscopy has allowed to notice colour deviation of the aged samples towards green and yellow, as well as lack of dye resistance to accelerated aging process. Thermographic analysis has shown no visible changes of the EA-TP surface and sub-surface during accelerated aging process. The aforementioned small changes on the surface of EA-TP did not affect the ballistic properties of composite armour. EA-TP insert maintains ballistic properties after accelerated aging process which was simulating the period of 6 years according to ASTM F1980 â 07:2002 standard