Puntos cuánticos: nueva aportación de la nanotecnología en investigación y medicina

Los Puntos Cuántico (PCs) son nanocristales más fotoestables, monocromáticos y brillantes que cualquier fluorocromo. Estas cualidades y su capacidad de formar múltiples constructos (funcionalización con anticuerpos, oligonucleótidos, Biotina, lectinas, iones magnéticos, etc.) les otorgan una enorme versatilidad analítica y una sensibilidad a nivel de molécula única. Además de mejorar determinaciones estándar como el PSA, los PCs ofrecen nuevas alternativas en Western blotting y citometría de flujo. La manufacturación de “laboratorios en un chip” es uno de los productos nanotecnológicos más destacados ya que permiten múltiples análisis simultáneos, a tiempo real, con un coste reducido y cantidades ínfimas de muestra. En el campo de la biotecnología los PCs son útiles en la identificación génica por código de barras multicolor en microchips. Los PCs unidos a ACs específicos permiten la detección por fluorescencia de diversas dianas en rutas metabólicas intracitoplasmáticas de células vivas sin alterar su fisiología. Más aún, permiten comprender, a la vez, el tráfico de proteínas, su localización, reciclaje y función en lo que se viene llamando Proteómica Visual. Nuevas aplicaciones en oncología clínica permiten identificar células cancerosas aisladas en sangre circulante y una mayor exactitud en el mapeado de Glanglio centinela en neoplasias de mama, así como conseguir discriminar selectivamente el nódulo tumoral en neurocirugía cerebral. ¿Estamos a las puertas del diagnóstico y terapia secuenciales por PCs en el mismo acto médico; biopsia óptica?. La medicina regenerativa promete terapias sustitutivas de órganos y tejidos generados “in vitro”. Los nanotubos de carbono actúan mejorando los sustratos para el crecimiento celular diferenciado de células madre. Además, son útiles para la liberación controlada de medicinas, en particular citoestáticos unidos a ACs oncoespecíficos, y como vehículo de vectores genéticos. La Nanotecnología y los Puntos Quánticos en particular representan el futuro del diagnóstico del laboratorio, la biología celular y la terapia oncológica.Quantum Dots (QDs) are more fotostable, monochromatic and brilliant than any standard fluorocrome. These qualities and their capacity to build different constructors (targeted with antibodies, oligonucleotides, Biotine, lectines, magnetic ions, etc) allow them a wide versatility and sensibility, even to single molecular levels. Furthermore, improving standard PSA and other tests QDs represent a new alternative in Western blotting and flow citometry. Laboratories-on-a-chip, one of the more original nanoproducts, makes possible a wide variety of clinical tests simultaneously at real time, low cost and a minimal amount of sample. QDs are also being employed in biotechnology to genetic identifications through multicolour barcodes on microchips. QDs nanocrystal–labeled antibodies allow simultaneous and safe detection of multiple molecules in metabolic tracts inside living cells. Even traffic, localization, turnover and function of proteins can be understood at a time, giving birth to Visual Proteomics. New implementations in clinical oncology enable cancer cells recognition in circulating blood, more precise identification of the sentinel node in breast neoplasia as well as selectively delimitate malignant growths in brain surgery. Are we close to a sequential diagnosis and therapy in a single medical act by Quantum Dots; the optical biopsy? Regenerative medicine promises replacement therapy of organs and tissues growth “in vitro”. Carbon Nanotubes improve the substratum to steam cells differentiation as well as under control drugs release, particularly targeted citostatics or genetic vectors. Nanotechnology and particularly Quantum Dots represent the future tools for laboratory diagnosis, cell biology and cancer therapy

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

Following oral administration, gastric emptying is often a rate-limiting step in the absorption of drugs and is dependent on both physiological and pharmaceutical factors. To guide translation into humans, small animal imaging during pre-clinical studies has been increasingly used to localise the gastrointestinal transit of solid dosage forms. In contrast to humans, however, anaesthesia is usually required for effective imaging in animals which may have unintended effects on intestinal physiology. This study evaluated the effect of anaesthesia and capsule size on the gastric emptying rate of coated capsules in rats. Computed tomography (CT) imaging was used to track and locate the capsules through the gastrointestinal tract. Two commercial gelatine mini-capsules (size 9 and 9h) were filled with barium sulphate (contrast agent) and coated using Eudragit L. Under the effect of anaesthesia, none of the capsules emptied from the stomach. In non-anaesthetised rats, most of the size 9 capsules did not empty from the stomach, whereas the majority of the smaller size 9h capsules successfully emptied from the stomach and moved into the intestine. This study demonstrates that even with capsules designed to empty from the stomach in rats, the gastric emptying of such solid oral dosage forms is not guaranteed. In addition, the use of anaesthesia was found to abolish gastric emptying of both capsule sizes. The work herein further highlights the utility of CT imaging for the effective visualisation and location of solid dosage forms in the intestinal tract of rats without the use of anaesthesia

Patient-Specific 3D Scanned and 3D Printed Antimicrobial Polycaprolactone Wound Dressings

The increasing prevalence of wound infections caused by antibiotic resistant bacteria is an urgent challenge facing modern medicine. To address this issue the expedient use of antimicrobial metals such as zinc, copper and silver were incorporated into an FDA-approved polymer (polycaprolactone - PCL) to produce filaments for 3D printing. These metals have broad-spectrum antimicrobial properties, and moreover, copper and zinc can enhance the wound healing process. 3D scanning was used to construct 3D models of a nose and ear to provide the opportunity to customize shape and size of a wound dressing to an individual patient. Hot melt extrusion was used to extrude pellets obtained by vacuum-drying of solutions of PCL and the different metals in order to manufacture metal-homogeneously-loaded filaments. Wound dressings with different shapes were produced with the filaments containing different concentrations of metals. Release of the metals from the dressings was determined by inductively coupled plasma atomic emission spectroscopy. All the different metal dressings show fast release (up to 24h) followed by slow release (up to 72h). The antibacterial efficacy of the wound dressings was tested using a thermal activity monitor system, revealing that silver and copper wound dressings had the most potent bactericidal properties. This study shows that 3D scanning and 3D printing, which are becoming simpler and more affordable, have the potential to offer solutions to produce personalised wound dressings

Tracking pollutants in a municipal sewage network impairing the operation of a wastewater treatment plant

This work provides a screening of organic contaminants and characterization of the dissolved organic matter in the sewer network until the municipal wastewater treatment plant (WWTP), identifying the network areas with a higher degree of contamination and their impact on the WWTP performance, particularly in the activated sludge reactor. Three monitoring campaigns were carried out at six selected locations of the sewage system (PVZ-1, PVZ-2, PS-F, PS-VC, CP-VC, and PS-T), influent (WWTPINF) and effluent (WWTPEFF) of the WWTP. Advanced analytical techniques were employed, namely excitation/emission matrix fluorescence-parallel factor analysis (EEM-PARAFAC), size exclusion chromatography with organic carbon detector (SEC-OCD), and liquid chromatography with high-resolution-mass spectrometric detection (LC-HRMS). EEM-PARAFAC showed higher fluorescence intensity for the protein-like component (C2), particularly at CP-VC (near seafood industries) associated with the presence of surfactants (~50 mg/L). SEC-OCD highlighted the WWTP efficiency in removing low molecular weight acids and neutrals. LC-HRMS tentatively identified 108 compounds of emerging concern (CEC) and similar detection patterns were obtained for all wastewater samples, except for PVZ-2 (lower detection), many of which occurred in the effluent. Eight CECs included on relevant Watch-Lists were detected in all WWTPEFF samples. Furthermore, 111 surfactants were detected, the classes more frequently found being alcohol ethoxylates (AEOs), nonylphenol polyethoxylates (NPEOs) and linear alkylbenzene sulphonates (LAS). The continuous presence of LAS and NPEOs allied to surfactants concentrations in the WWTPINF of 15–20 mg/L, with CP-VC location (linked with food industries) as an important contributor, explain the morphological changes in the activated sludge and high LAS content in the dewatered sludge, which may have impacted WWTP performance.i) Base-UIDB/50020/2020 and Programmatic-UIDP/50020/2020 Funding of LSRE-LCM, funded by national funds through FCT/MCTES (PIDDAC); ii) European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P); iii) Xunta de Galicia (Verónica Castro predoctoral contract: ED481A-2017/156, and ED431C2017/36), the Spanish Agencia Estatal de Investigación – MCIN/AEI/ 10.13039/501100011033 (ref. PID2020-117686RB-C32); iv) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF), through North Portugal Regional Operational Programme (NORTE2020), under the PORTUGAL 2020 Partnership Agreement. The authors also acknowledge Águas do Norte, S.A. for supporting the development of this work. Daniela F.S. Morais acknowledges her Ph.D. scholarship supported by FCT (SFRH/BD/146476/2019). Bianca M. Souza Chaves gratefully acknowledges her postdoctoral scholarship supported by CNPq through the Science Without Borders Program (Process No. 201989/2014-0). Vítor J.P. Vilar acknowledges the FCT Individual Call to Scientific Employment Stimulus 2017 (CEECIND/01317/2017)S

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III