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1.
Can Pharm J (Ott) ; 153(5): 301-307, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33110471

RESUMEN

BACKGROUND: Multiple medication changes during hospitalization increase the risk of errors upon discharge. Community pharmacists may face barriers to providing pharmaceutical care because of the lack of clinical information and communication from hospitals. Studies implementing handover to community pharmacists upon hospital discharge reported improved patient outcomes, but interventions were time-consuming. METHODS: One-on-one interviews and a focus group were conducted to identify community pharmacists' barriers to providing care to patients recently discharged from hospital and to determine their preferences for hospital discharge prescriptions. Transcripts were qualitatively analyzed using an inductive semantic approach. RESULTS: Four one-on-one interviews and an 8-participant focus group were conducted. Participants described barriers to providing care to discharged patients, including lack of communication, incomplete prescriptions, and limited clinical information. Participants identified that the most valuable information to include comprised laboratory values, hospital contact information and annotation of medication changes. These items would improve their abilities to provide timely and high-quality pharmaceutical care. INTERPRETATION: Our results were similar to prior literature identifying a lack of communication and clinical information as barriers to providing care to recently discharged patients. Unexpectedly, study participants did not rate medication indication as a strongly preferred information item. CONCLUSIONS: Hospital discharge prescriptions lack information, which makes it challenging for community pharmacists to provide pharmaceutical care. Discharge prescriptions should include additional clinical information. Can Pharm J (Ott) 2020;153:xx-xx.

2.
Appl Opt ; 57(25): 7377, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-30182958

RESUMEN

This erratum is submitted to correct information regarding Fig. 8 of Appl. Opt.57, E142 (2018)APOPAI0003-693510.1364/AO.57.00E142.

3.
Appl Opt ; 57(22): E142-E146, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30117912

RESUMEN

The characterization of an amplified piezoelectric actuator (APA) as a new axial scanning method for multiple-reference optical coherence tomography (MR-OCT) is described. MR-OCT is a compact optical imaging device based on a recirculating reference-arm-scanning optical delay using a partial mirror that can enhance the imaging depth range by more than 10 times the reference mirror's scanning amplitude. The scanning amplitude of the used APA was varied between 30 µm and 250 µm, depending on the scanning frequency of between 0.8 kHz and 1.2 kHz. A silver-coated miniature mirror was attached to the APA via ultraviolet-cured optical adhesive, and the light source was a super-luminescent diode with 1310 nm center wavelength and 56 nm bandwidth. The sensitivity was measured with and without the partial mirror in the reference delay line as a function of scan speed, frequency, and range, therefore providing results for MR-OCT and TD-OCT modes. It was found that the APA provides more than twice the mechanical scanning range compared to other opto-mechanic actuators, but results indicate degradation of signal-to-noise ratio and sensitivity at larger imaging depths. In conjunction with MR-OCT, the scan range of maximum 200 µm can be enhanced up to 1-1.5 mm by using a reduced amount of orders of reflections, which could be of interest to increase sensitivity in the future.

4.
Pharm Res ; 34(7): 1469-1476, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28508123

RESUMEN

PURPOSE: To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS: Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. CONCLUSION: This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates.


Asunto(s)
Flurbiprofeno/efectos de la radiación , Naproxeno/efectos de la radiación , Ácidos Polimetacrílicos/efectos de la radiación , Antiinflamatorios no Esteroideos/química , Portadores de Fármacos , Liberación de Fármacos , Flurbiprofeno/administración & dosificación , Flurbiprofeno/química , Humanos , Naproxeno/administración & dosificación , Naproxeno/química , Procesos Fotoquímicos , Fotólisis , Ácidos Polimetacrílicos/química , Rayos Ultravioleta
5.
Mol Pharm ; 13(8): 2817-22, 2016 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-27359363

RESUMEN

Infection is an inevitable consequence of chronic urinary catheterization with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterized patients. In this work, we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for "intelligent" antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalized nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7 and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development toward the prevention of catheter-associated urinary tract infections in vivo.


Asunto(s)
Adhesión Bacteriana/efectos de los fármacos , Materiales Biocompatibles/química , Metacrilatos/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Materiales Biocompatibles/farmacología , Biopelículas/efectos de los fármacos , Infecciones Relacionadas con Catéteres/prevención & control , Ácido Nalidíxico/química , Ácido Nalidíxico/farmacología , Infecciones Urinarias/prevención & control
6.
Mol Pharm ; 12(8): 2928-36, 2015 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-26111258

RESUMEN

This paper presents a novel strategy for the prevention of ventilator-associated pneumonia that involves coating poly(vinyl chloride, PVC) endotracheal tubes (ET) with hydrogels that may be subsequently used to entrap nebulized antimicrobial solutions. Candidate hydrogels were prepared containing a range of ratios of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) from 100:0 to 70:30 using free radical polymerization and, when required, simultaneous attachment to PVC was performed. The mechanical properties, glass transition temperatures, swelling kinetics, uptake of gentamicin from an aqueous medium, and gentamicin release were characterized. Increasing the MAA content of the hydrogels significantly decreased the ultimate tensile strength, % elongation at break, Young's modulus, and increased the glass transition temperature, the swelling ratio, and gentamicin uptake. Microbial (Staphylococcus aureus and Pseudomonas aeruginosa) adherence to control (drug-free) hydrogels was observed; however, while adherence to gentamicin-containing p(HEMA) occurred, no adherence occurred to gentamicin-containing HEMA:MAA copolymers. Antimicrobial persistence of gentamicin-containing hydrogels was examined by determining the zone of inhibition against each microorganism on successive days. Hydrogel composition affected the observed antimicrobial persistence, with the hydrogel composed of 70:30 HEMA:MAA exhibiting >20 days persistence against S. aureus and P. aeruginosa, respectively. To simulate clinical use, the hydrogels (coated onto PVC) were first exposed to a nebulized solution of gentamicin (4 mL, 80 mg for 20 min), and then to nebulized bacteria (4 mL ca. 1×10(9) colony forming units mL(-1), 30 min). Viable bacteria were not observed on the gentamicin-treated p(HEMA: MAA) copolymers, whereas growth was observed on gentamicin-treated p(HEMA). In light of the excellent antimicrobial activity and physicochemical properties, p(HEMA: MAA) copolymers composed of ratios of 80:20 or 70:30 HEMA: MAA were identified as potentially useful coatings of endotracheal tubes to be used in conjunction with the clinical nebulization of gentamicin and designed for the prevention of ventilator-associated pneumonia.


Asunto(s)
Materiales Biocompatibles/química , Gentamicinas/farmacología , Hidrogeles/química , Neumonía Asociada al Ventilador/prevención & control , Polímeros/química , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Humanos , Intubación Intratraqueal , Cinética , Neumonía Asociada al Ventilador/microbiología , Tensoactivos/química , Temperatura , Resistencia a la Tracción
7.
J Pept Sci ; 21(10): 770-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26310860

RESUMEN

The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost-effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Cinamatos/química , Péptidos/química , Péptidos/farmacología , Antibacterianos/efectos adversos , Materiales Biocompatibles , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Péptidos/efectos adversos , Staphylococcus aureus/efectos de los fármacos
8.
Ann Pharmacother ; 49(6): 656-69, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25780250

RESUMEN

BACKGROUND: Key performance indicators (KPIs) are quantifiable measures of quality. There are no published, systematically derived clinical pharmacy KPIs (cpKPIs). OBJECTIVE: A group of hospital pharmacists aimed to develop national cpKPIs to advance clinical pharmacy practice and improve patient care. METHODS: A cpKPI working group established a cpKPI definition, 8 evidence-derived cpKPI critical activity areas, 26 candidate cpKPIs, and 11 cpKPI ideal attributes in addition to 1 overall consensus criterion. Twenty-six clinical pharmacists and hospital pharmacy leaders participated in an internet-based 3-round modified Delphi survey. Panelists rated 26 candidate cpKPIs using 11 cpKPI ideal attributes and 1 overall consensus criterion on a 9-point Likert scale. A meeting was facilitated between rounds 2 and 3 to debate the merits and wording of candidate cpKPIs. Consensus was reached if 75% or more of panelists assigned a score of 7 to 9 on the consensus criterion during the third Delphi round. RESULTS: All panelists completed the 3 Delphi rounds, and 25/26 (96%) attended the meeting. Eight candidate cpKPIs met the consensus definition: (1) performing admission medication reconciliation (including best-possible medication history), (2) participating in interprofessional patient care rounds, (3) completing pharmaceutical care plans, (4) resolving drug therapy problems, (5) providing in-person disease and medication education to patients, (6) providing discharge patient medication education, (7) performing discharge medication reconciliation, and (8) providing bundled, proactive direct patient care activities. CONCLUSIONS: A Delphi panel of hospital pharmacists was successful in determining 8 consensus cpKPIs. Measurement and assessment of these cpKPIs will serve to advance clinical pharmacy practice and improve patient care.


Asunto(s)
Conciliación de Medicamentos/métodos , Farmacéuticos/organización & administración , Servicio de Farmacia en Hospital/organización & administración , Consenso , Técnica Delphi , Humanos , Alta del Paciente , Farmacéuticos/normas , Servicio de Farmacia en Hospital/normas
9.
Mar Drugs ; 13(1): 1-28, 2014 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-25546516

RESUMEN

Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs). Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI) activity against acyl homoserine lactone (AHL)-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (-63%) and in pre-established, mature P. aeruginosa PAO1 biofilms (-33%). KS8 supernatant also caused a 0.97-log reduction (-89%) and a 2-log reduction (-99%) in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC) of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC) was observed over the concentration range tested (MBC > 16 mg/mL). Sub-MIC concentrations (1 mg/mL) of KS8 crude organic extract significantly reduced the quorum sensing (QS)-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments.


Asunto(s)
Antibacterianos/farmacología , Pseudoalteromonas/química , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Tobramicina/farmacología , Biopelículas , Chromobacterium/metabolismo , Pruebas de Sensibilidad Microbiana , Agua de Mar/microbiología
10.
Can J Hosp Pharm ; 77(1): e3490, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357298

RESUMEN

Background: Patients who report penicillin allergies may receive alternative antibiotics. Such substitution contributes to antimicrobial resistance, lower treatment efficacy, increased frequency of adverse events, and increased costs. Approximately 90% of individuals who report a penicillin allergy can tolerate a penicillin. Objective: To identify the barriers to and facilitators of removal by health care workers of inaccurate antimicrobial allergies from patient records, known as delabelling. Data Sources: The MEDLINE database was searched from inception to December 29, 2020. Study Selection and Data Extraction: Qualitative studies evaluating health care professionals' perceptions of barriers to and/or facilitators of the act of delabelling a patient's antimicrobial allergies were included in the meta-synthesis. Data Synthesis: The Theoretical Domains Framework was used to code and group individual utterances from the included studies, which were mapped to the Behaviour Change Wheel and corresponding intervention function and policy categories. Results: Four studies met the inclusion criteria. Eight themes were identified as representing barriers to delabelling: delabelling skills, patient education skills, knowledge, electronic health records (EHRs), communication frameworks, time, fear about allergic reactions, and professional roles. Behaviour change interventions that may overcome these barriers include education, training, algorithms and toolkits, changes to EHRs, use of dedicated personnel, policies, incentivization of correct labelling, and an audit system. Conclusions: Eight themes were identified as barriers to delabelling of antimicrobial allergies. Future behaviour change interventions to address these barriers were proposed. Confidence in the findings of this study was judged to be moderate, according to the GRADE CERQual approach.


Contexte: Les patients qui signalent des allergies à la pénicilline peuvent recevoir d'autres antibiotiques. Une telle substitution contribue à la résistance aux antimicrobiens, à une moindre efficacité du traitement, à une fréquence accrue des événements indésirables et à une augmentation des coûts. Environ 90 % des personnes qui déclarent une allergie à la pénicilline peuvent la tolérer. Objectif: Identifier les obstacles à l'élimination par les travailleurs de la santé des allergies antimicrobiennes inexactes des dossiers des patients, ce que l'on appelle « le désétiquetage ¼, et les facteurs qui le favorisent. Sources des données: La base de données MEDLINE a été consultée depuis sa création jusqu'au 29 décembre 2020. Sélection de l'étude et extraction des données: Des études qualitatives évaluant les perceptions des professionnels de la santé quant aux obstacles à l'acte de désétiquetage des allergies aux antimicrobiens d'un patient et les facilitateurs de celui-ci ont été incluses dans la métasynthèse. Synthèse des données: Le cadre théorique des domaines a été utilisé pour coder et regrouper les énoncés individuels, qui ont ensuite été associés à la roue du changement de comportement ainsi qu'aux catégories de fonctions et de politiques d'intervention correspondantes. Résultats: Quatre études répondaient aux critères d'inclusion. Huit thèmes ont été identifiés comme représentant des obstacles au désétiquetage: les compétences en la matière, les compétences en matière d'éducation des patients, les connaissances, les dossiers de santé électroniques (DSE), les cadres de communication, le temps, la peur des réactions allergiques et les rôles professionnels. Les interventions visant le changement de comportement qui peuvent surmonter ces obstacles comprennent l'éducation, la formation, les algorithmes et les boîtes à outils de désétiquetage, la modification des DSE, le recours à du personnel dédié, des politiques, l'incitation à un étiquetage correct et un système d'audit. Conclusions: Huit thèmes ont été identifiés comme étant des obstacles au désétiquetage des allergies aux antimicrobiens. De futures interventions ciblant le changement de comportement pour les surmonter ont été proposées. La confiance dans les résultats de cette étude a été jugée modérée, selon l'approche GRADE CERQual.

11.
J Neurol ; 271(4): 1873-1884, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38091087

RESUMEN

OBJECTIVES: We report routinely collected outcome data from an 8-week outpatient rehabilitative therapy program. The aims of the intervention were to (1) reduce symptom severity and (2) improve functional mobility in adults with functional neurological disorder (FND). METHODS: The program delivered individual physiotherapy, cognitive behavioral therapy (CBT) and self-management sessions, group physiotherapy, and psychoeducation. Outcome measures included the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Work and Social Adjustment Scale (WSAS), 10-Meter Walk Test (10MWT), Timed Up and Go (TUG), and Berg Balance Scale (BBS). Data were analyzed retrospectively in accordance with routine service evaluation. Wilcoxon signed-rank tests assessed changes in outcomes between weeks 1 and 8 for all patients completing treatment (n = 45). For patients who attended the 3-month follow-up (n = 31), Friedman's ANOVA assessed overall change in outcomes over time. Post hoc Wilcoxon signed-rank tests compared pairs of time-points (Weeks 1, 8, and 3-month follow-up). RESULTS: Analyses of patients completing the program revealed significant improvements in scores between week 1 and week 8. Excluding the BBS, there were statistically significant improvements in all outcomes between weeks 1 and 8 and between weeks 1 and 3-month follow-up. DISCUSSION: This outpatient therapy program provided effective treatment for FND. Patients reported reduced anxiety, depression, and functional impairment, as well as improved performance on most physiotherapy measures.


Asunto(s)
Terapia Cognitivo-Conductual , Trastornos de Conversión , Adulto , Humanos , Pacientes Ambulatorios , Estudios Retrospectivos , Resultado del Tratamiento
12.
Pharm Res ; 30(3): 857-65, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23229857

RESUMEN

PURPOSE: The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve 'intelligent' drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection. METHODS: p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis. RESULTS: The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH-responsive behavior, but additionally exhibited a sustained period of zero-order release. CONCLUSIONS: The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an 'intelligent', infection-responsive, self-sterilizing biomaterial.


Asunto(s)
Antiinfecciosos/administración & dosificación , Preparaciones de Acción Retardada/química , Metacrilatos/química , Ácido Nalidíxico/administración & dosificación , Antiinfecciosos/farmacología , Materiales Biocompatibles/química , Humanos , Hidrogeles/química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ácido Nalidíxico/farmacología , Infecciones por Proteus/tratamiento farmacológico , Proteus mirabilis/efectos de los fármacos , Termodinámica
14.
Matrix Biol ; 115: 48-70, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36435425

RESUMEN

Cerebral small vessel disease (CSVD) is a leading cause of stroke and vascular cognitive impairment and dementia. Studying monogenic CSVD can reveal pathways that are dysregulated in common sporadic forms of the disease and may represent therapeutic targets. Mutations in collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause highly penetrant CSVD as part of a multisystem disorder referred to as Gould syndrome. COL4A1 and COL4A2 form heterotrimers [a1α1α2(IV)] that are fundamental constituents of basement membranes. However, their functions are poorly understood and the mechanism(s) by which COL4A1 and COL4A2 mutations cause CSVD are unknown. We used histological, molecular, genetic, pharmacological, and in vivo imaging approaches to characterize central nervous system (CNS) vascular pathologies in Col4a1 mutant mouse models of monogenic CSVD to provide insight into underlying pathogenic mechanisms. We describe developmental CNS angiogenesis abnormalities characterized by impaired retinal vascular outgrowth and patterning, increased numbers of mural cells with abnormal morphologies, altered contractile protein expression in vascular smooth muscle cells (VSMCs) and age-related loss of arteriolar VSMCs in Col4a1 mutant mice. Importantly, we identified elevated TGFß signaling as a pathogenic consequence of Col4a1 mutations and show that genetically suppressing TGFß signaling ameliorated CNS vascular pathologies, including partial rescue of retinal vascular patterning defects, prevention of VSMC loss, and significant reduction of intracerebral hemorrhages in Col4a1 mutant mice aged up to 8 months. This study identifies a novel biological role for collagen α1α1α2(IV) as a regulator of TGFß signaling and demonstrates that elevated TGFß signaling contributes to CNS vascular pathologies caused by Col4a1 mutations. Our findings suggest that pharmacologically suppressing TGFß signaling could reduce the severity of CSVD, and potentially other manifestations associated with Gould syndrome and have important translational implications that could extend to idiopathic forms of CSVD.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Colágeno Tipo IV , Animales , Ratones , Membrana Basal/metabolismo , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Mutación , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Modelos Animales de Enfermedad
15.
Invest Ophthalmol Vis Sci ; 64(4): 30, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37097227

RESUMEN

Purpose: The unfolded protein response (UPR) is triggered when the protein folding capacity of the endoplasmic reticulum (ER) is overwhelmed and misfolded proteins accumulate in the ER, a condition referred to as ER stress. IRE1α is an ER-resident protein that plays major roles in orchestrating the UPR. Several lines of evidence implicate the UPR and its transducers in neurodegenerative diseases, including retinitis pigmentosa (RP), a group of inherited diseases that cause progressive dysfunction and loss of rod and cone photoreceptors. This study evaluated the contribution of IRE1α to photoreceptor development, homeostasis, and degeneration. Methods: We used a conditional gene targeting strategy to selectively inactivate Ire1α in mouse rod photoreceptors. We used a combination of optical coherence tomography (OCT) imaging, histology, and electroretinography (ERG) to assess longitudinally the effect of IRE1α deficiency in retinal development and function. Furthermore, we evaluated the IRE1α-deficient retina responses to tunicamycin-induced ER stress and in the context of RP caused by the rhodopsin mutation RhoP23H. Results: OCT imaging, histology, and ERG analyses did not reveal abnormalities in IRE1α-deficient retinas up to 3 months old. However, by 6 months of age, the Ire1α mutant animals showed reduced outer nuclear layer thickness and deficits in retinal function. Furthermore, conditional inactivation of Ire1α in rod photoreceptors accelerated retinal degeneration caused by the RhoP23H mutation. Conclusions: These data suggest that IRE1α is dispensable for photoreceptor development but important for photoreceptor homeostasis in aging retinas and for protecting against ER stress-mediated photoreceptor degeneration.


Asunto(s)
Degeneración Retiniana , Retinitis Pigmentosa , Animales , Ratones , Envejecimiento , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Degeneración Retiniana/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Respuesta de Proteína Desplegada , Estrés del Retículo Endoplásmico
16.
Ann Pharmacother ; 46(3): e6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22388329

RESUMEN

OBJECTIVE: To report a case of methylene blue extravasation and subsequent tissue necrosis in a patient with refractory septic shock. CASE SUMMARY: A 47-year-old female presented with febrile neutropenia secondary to chemotherapy. The patient quickly decompensated to refractory septic shock in the critical care unit despite implementation of early goal-directed therapy as well as intravenous norepinephrine and vasopressin to stabilize her hemodynamic status. She received a 16-hour infusion of 1% methylene blue 0.25 mg•kg(-1)•h(-1), titrated up to 0.5 mg•kg(-1)•h(-1), via a peripheral intravenous catheter. Ten hours after the start of the methylene blue infusion, she experienced a local extravasation injury, which led to distal digital necrosis. While her hemodynamic status improved dramatically, allowing discharge from the intensive care unit and eventually to home, the extravasation site became necrotic and required debridement and skin graft. DISCUSSION: Methylene blue is a vasoactive chemical that has been shown to provide hemodynamic stability in the treatment of refractory septic shock. Methylene blue administration is not considered standard of practice in the treatment of refractory septic shock and many aspects of its dosing, route, duration, and adverse effects are poorly described. As such, there is little guidance for its administration. We postulate that, in our patient, in the presence of systemic vasopressin and norepinephrine, methylene blue caused extensive vasoconstriction at the site of extravasation, resulting in tissue ischemia and necrosis. Tissue necrosis secondary to peripheral intravenous extravasation has not been previously described and is not listed as an adverse outcome on the drug monograph. The Naranjo probability scale indicates that the tissue necrosis was probably caused by the methylene blue extravasation. CONCLUSIONS: To mitigate future risk to limb and skin, we recommend that methylene blue infusions be delivered via central venous catheter. Extra care should be given to patients with risk factors for extravasation, such as sedation, presence of systemic disease, proximal intravenous puncture sites, and improperly placed catheters.


Asunto(s)
Azul de Metileno/efectos adversos , Choque Séptico/tratamiento farmacológico , Femenino , Humanos , Infusiones Intravenosas , Isquemia/inducido químicamente , Azul de Metileno/administración & dosificación , Persona de Mediana Edad , Necrosis/inducido químicamente , Choque Séptico/patología , Piel/efectos de los fármacos , Piel/patología , Vasoconstricción
17.
Eplasty ; 22: e46, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408121

RESUMEN

Background: Postoperative complications associated with seroma formation resulting from surgical dead space continue to present a challenge in modern surgery. There is an unmet need for new technologies that address surgical dead space as well as prevent seroma formation and associated downstream postoperative complications. Methods: The novel implantable tissue apposition and drainage system ENIVO was developed and tested in a bilateral ovine external abdominal oblique (EAO) resection model of surgical dead space. The ENIVO system is a portable powered pump and wound interface featuring air-purged vacuum closure (APVC) that delivers a sustained level of vacuum pressure (80 and 100 mmHg) to the treatment site with an intermittent burst of sterile filtered air through the implanted wound interface. Seroma area, seroma volume, and drain migration were assessed at postoperative days 7 and 14, and all animals were euthanized at day 28 with gross assessment of treatment efficacy including the presence of residual seroma and tissue apposition. Results: The bilateral model created relatively uniform defects of ~120 cm2 following excision of ~30 to 50 g of EAO muscle. Median seroma area of ENIVO-treated defects was statistically smaller than standard of care (SoC)-treated defects at days 7 and 14. Median seroma volume at 14 days was significantly reduced in ENIVO-treated defects relative to SoC-treated defects [1.3 (IQR 0.0-79.5) mL and 188.5 (IQR 27.6-342.9) mL, respectively]. At postoperative day 28, 40% (n = 4/10) of SoC defects showed a residual seroma, whereas in contrast, none of the ENIVO-treated defects showed signs of a residual seroma. Median tissue apposition scoring was higher in the ENIVO treatment group [3 (IQR 3-3)] compared with the SoC group [3 (IQR 0-3)]. Conclusions: The ENIVO system represents a new approach to dead space management and seroma prevention and was shown to outperform a SoC surgical drain in a challenging large defect model of surgical dead space management and seroma prevention.

18.
Int J Mol Sci ; 12(10): 6566-96, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22072905

RESUMEN

Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/química , Desinfectantes/química , Péptidos Catiónicos Antimicrobianos/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Bacterias/metabolismo , Membrana Celular/metabolismo , Pared Celular/metabolismo , Desinfectantes/metabolismo , Desinfectantes/farmacología , Diseño de Fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Hemólisis/efectos de los fármacos , Lipopéptidos/química , Lipopéptidos/farmacología
19.
Int J Antimicrob Agents ; 58(1): 106360, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33992750

RESUMEN

BACKGROUND: Bacterial spores are an important consideration in healthcare decontamination, with cross-contamination highlighted as a major route of transmission due to their persistent nature. Their containment is extremely difficult due to the toxicity and cost of first-line sporicides. METHODS: Susceptibility of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli to phenothiazinium photosensitizers and cationic surfactants under white- or red-light irradiation was assessed by determination of minimum inhibitory concentrations, minimum bactericidal concentrations and time-kill assays. B. subtilis spore eradication was assessed via time-kill assays, with and without nutrient and non-nutrient germinant supplementation of photosensitizer, surfactant and photosensitizer-surfactant solutions in the presence and absence of light. RESULTS: Under red-light irradiation, >5-log10 colony-forming units/mL reduction of vegetative bacteria was achieved within 10 min with toluidine blue O (TBO) and methylene blue (MB). Cationic surfactant addition did not significantly enhance spore eradication by photosensitizers (P>0.05). However, addition of a nutrient germinant mixture to TBO achieved a 6-log10 reduction after 20 min of irradiation, while providing 1-2 log10 improvement in spore eradication for MB and pyronin Y. CONCLUSIONS: Light-activated photosensitizer solutions in the presence of surfactants and germination-promoting agents provide a highly effective method to eradicate dormant and vegetative bacteria. These solutions could provide a useful alternative to traditional chemical agents used for high-level decontamination and infection control within health care.


Asunto(s)
Bacterias/efectos de los fármacos , Desinfectantes/farmacología , Equipos y Suministros/microbiología , Fármacos Fotosensibilizantes/farmacología , Esporas Bacterianas/efectos de los fármacos , Esterilización/métodos , Tensoactivos/farmacología , Bacillus subtilis/efectos de los fármacos , Infecciones Bacterianas/prevención & control , Infección Hospitalaria/prevención & control , Escherichia coli/efectos de los fármacos , Humanos , Luz , Azul de Metileno/farmacología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pironina/farmacología , Staphylococcus aureus/efectos de los fármacos , Cloruro de Tolonio/farmacología
20.
Int J Clin Pharm ; 43(3): 748-752, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33515356

RESUMEN

Background Hospital pharmacy audit and feedback of 'do not use' medication abbreviations improves patient safety. For audit and feedback systems to be effective, the data captured must be of high quality such that end-users trust the information to guide practice change. The quality of data captured during monthly standardized pharmacy 'do not use' abbreviation audits is currently unknown. Objective We aimed to assess pharmacy 'do not use' abbreviation audit data quality. Method Primary audit data quality was assessed by examining a random sample of handwritten medication prescriptions for the presence and type of 'do not use' abbreviations. This data was compared with the pharmacy monthly audit data to determine data capture agreement and consistency over time. Results There were 1132 prescriptions from July, October, and December 2019 included. Data capture agreement between the pharmacy audit and the secondary assessment using Cohen's Kappa ranged from 0.53 to 0.63. The primary audit under-reported 'do not use' abbreviation rates, however this did not vary over time (χ2 = 1.215, p = 0.545). Conclusion Pharmacy staff audits under-reported 'do not use' abbreviation rates, however this was consistent over time. The quality of pharmacy audits should be assessed and disseminated to end-users prior to implementing feedback.


Asunto(s)
Prescripciones de Medicamentos , Servicios Farmacéuticos , Retroalimentación , Hospitales , Humanos , Auditoría Médica , Seguridad del Paciente
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