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1.
Pharmacy (Basel) ; 8(4)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187105

RESUMO

(1) Background: Sepsis is the leading cause of maternal death in 11-15% of women worldwide. This emphasises the importance of administrating timely and appropriate antibiotic therapy to women with sepsis. We aimed to evaluate the appropriateness of antimicrobial prescribing in women diagnosed with peripartum sepsis. (2) Method: A prospective observational cohort study in a single Scottish health region with 12,233 annual live births. Data were collected on women diagnosed with sepsis in the peripartum period using physical and electronic medical records, drug Kardex® (medication administration) and ward handover records. (3) Results: A sepsis diagnosis was concluded in 89 of the 2690 pregnancy cases reviewed, with a median hospital stay of four days. Good overall adherence to the local guidelines for the empiric antimicrobial treatment of sepsis was observed. Group B Streptococcus was associated with 20.8% of maternal sepsis cases, whilst in 60% of clinical specimens tested no causative pathogen was isolated. (4) Conclusion: The lack of specific and sensitive clinical markers for sepsis, coupled with their inconsistent clinical application to inform diagnosis, hindered effective antimicrobial stewardship. This was further exacerbated by the lack of positive culture isolates from clinical specimens, which meant that patients were often continued on broader-spectrum empiric treatment.

2.
Exp Parasitol ; 220: 108033, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166530

RESUMO

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

3.
Saudi Pharm J ; 28(11): 1492-1498, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33250656

RESUMO

Background: Antimicrobial resistance (AMR) is presently considered an emergent major global public health concern and excessive and/or inappropriate use of broad-spectrum antimicrobials contribute to the development of AMR. Objective: To evaluate the appropriateness of carbapenems and piperacillin-tazobactam use in a tertiary care hospital. Methods: A retrospective, observational, cross-sectional, drug-utilization study was conducted. The study included all adult hospitalized patients who had received at least one dose of the antimicrobials during their admission for the period between 1 January 2016 and 31 December 2017. The appropriateness of antimicrobial therapy was evaluated according to the Infectious Diseases Society of America (IDSA) guidelines with the consideration of the institutional antibiogram. Results: Overall, 2731 patients received 5005 courses with one of the antimicrobials, for a total of 5045.9 defined daily doses (DDD) of imipenem-cilastatin, 6492.3 of meropenem and 15,595 of piperacillin-tazobactam (4.93, 6.34 and 15.24 DDD/100 bed days, respectively). The mean age of the patients who received either antimicrobial was 55.5 ± 20.3 years, with a 14-day average length of hospital stay. About half (52%) of the prescriptions were written for patients treated in the medical ward. Pneumonia (26.6%) and sepsis (24.9%) were the most common indication for the initiation of antimicrobial therapy. Of the assessed prescriptions, only 2787 (56.5%) were prescribed appropriately, with 2142 (43.5%) deemed inappropriate. The three most common reasons for inappropriate prescription were: the spectrum of activity was too broad (44.6%), followed by antimicrobial use without culture request (32.4%), and failure of suitable antimicrobial de-escalation (19.9%). Conclusions: The study indicates that the overall rate of inappropriateness was high, emphasizing the need to develop initiatives to effectively improve broad-spectrum antimicrobial prescribing.

4.
Healthcare (Basel) ; 8(4)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019491

RESUMO

Background: In 2014, the Sepsis Six Care Bundle (SSCB) was introduced into a Scottish health region to improve patient outcomes. Poor compliance was demonstrated with the SSCB across different specialities. This study explored determinants of non-compliance with the SSCB in maternity wards. Methods: In-depth interviews were conducted with midwives in a single Scottish health region. Convenience sampling was used to recruit interviewees. The interviews were digitally recorded, transcribed verbatim, entered into NVivo software, and analysed using thematic analysis. Results: Thirteen face-to-face interviews were completed and lasted an average of 33 min. Three main barriers were identified to SSCB implementation; the difficulty of diagnosing sepsis, the suitability of the SSCB in a maternity setting as part of the pre-conditions phase, and the lack of staff training as part of the pre-implementation phase. Conclusion: The findings emphasize the importance of adapting improvement initiatives with sufficient preparation of staff in the rationale use to the context of care bundles.

5.
Cancers (Basel) ; 11(10)2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635032

RESUMO

Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The 'omics' technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based metabolomics is a promising method to investigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this study, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to investigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing surgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma samples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were highly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline, Hexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for eight weight-losing samples (≥5% weight loss) and nine weight-stable samples (<5%weight loss) between predicted and actual weight change (r = 0.976, p = 0.0014). Overall, 40 metabolites were associated with ≥5% weight loss. This study provides biological validation of the consensus definition of cancer cachexia (Fearon et al.) and provides feasible candidate markers for further investigation in early diagnosis and the assessment of therapeutic intervention.

6.
J Liposome Res ; 29(3): 229-238, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30296860

RESUMO

RNA interference is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics.


Assuntos
Técnicas de Silenciamento de Genes/métodos , Lipossomos/química , Nanocápsulas/química , RNA Interferente Pequeno/administração & dosagem , Tensoativos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Inativação Gênica , Técnicas de Transferência de Genes , Luciferases/genética , Luciferases/metabolismo , Melanoma Experimental , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estudo de Prova de Conceito , RNA Interferente Pequeno/metabolismo
7.
J Antimicrob Chemother ; 73(8): 2223-2230, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800290

RESUMO

Background: Concern about increasing carbapenem and piperacillin/tazobactam use led the Scottish Antimicrobial Prescribing Group (SAPG) to develop national guidance on optimal use of these agents, and to implement a quality improvement programme to assess the impact of guidance on practice. Objectives: To evaluate how SAPG guidance had been implemented by health boards, assess how this translated into clinical practice, and investigate clinicians' views and behaviours about prescribing carbapenems and alternative agents. Methods: Local implementation of SAPG guidance was assessed using an online survey. A bespoke point prevalence survey was used to evaluate prescribing. Clinicians' experience of using carbapenems and alternatives was examined through semi-structured interviews. National prescribing data were analysed to assess the impact of the programme. Results: There were greater local restrictions for carbapenems than for piperacillin/tazobactam. Laboratory result suppression was inconsistent between boards and carbapenem-sparing antibiotics were not widely available. Compliance with local guidelines was good for meropenem but lower for piperacillin/tazobactam. Indication for use was well documented but review/stop dates were poorly documented for both antibiotics. Decisions to prescribe a carbapenem were influenced by local guidelines and specialist advice. Many clinicians lacked confidence to de-escalate treatment. Use of both antibiotics decreased during the course of the programme. Conclusions: A multifaceted quality improvement programme was used to gather intelligence, promote behaviour change, and focus interventions on the use of carbapenems and piperacillin/tazobactam. Use of these antimicrobials decreased during the programme-a trend not seen elsewhere in Europe. The programme could be generalized to other antimicrobials.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Uso de Medicamentos/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Política de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Escócia , Inquéritos e Questionários , Adulto Jovem
8.
Metabolites ; 8(1)2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29438325

RESUMO

Metabolomic profiling of nine trained ultramarathon runners completing an 80.5 km self-paced treadmill-based time trial was carried out. Plasma samples were obtained from venous whole blood, collected at rest and on completion of the distance (post-80.5 km). The samples were analyzed by using high-resolution mass spectrometry in combination with both hydrophilic interaction (HILIC) and reversed phase (RP) chromatography. The extracted putatively identified features were modeled using Simca P 14.1 software (Umetrics, Umea, Sweden). A large number of amino acids decreased post-80.5 km and fatty acid metabolism was affected with an increase in the formation of medium-chain unsaturated and partially oxidized fatty acids and conjugates of fatty acids with carnitines. A possible explanation for the complex pattern of medium-chain and oxidized fatty acids formed is that the prolonged exercise provoked the proliferation of peroxisomes. The peroxisomes may provide a readily utilizable form of energy through formation of acetyl carnitine and other acyl carnitines for export to mitochondria in the muscles; and secondly may serve to regulate the levels of oxidized metabolites of long-chain fatty acids. This is the first study to provide evidence of the metabolic profile in response to prolonged ultramarathon running using an untargeted approach. The findings provide an insight to the effects of ultramarathon running on the metabolic specificities and alterations that may demonstrate cardio-protective effects.

9.
J Mater Sci ; 53(5): 3198-3209, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31997831

RESUMO

Polydopamine has been found to be a biocompatible polymer capable of supporting cell growth and attachment, and to have antibacterial and antifouling properties. Together with its ease of manufacture and application, it ought to make an ideal biomaterial and function well as a coating for implants. In this paper, atomic force microscope was used to measure the adhesive forces between polymer-, protein- or polydopamine-coated surfaces and a silicon nitride or polydopamine-functionalised probes. Surfaces were further characterised by contact angle goniometry, and solutions by circular dichroism. Polydopamine was further characterised with infrared spectroscopy and Raman spectroscopy. It was found that polydopamine functionalisation of the atomic force microscope probe significantly reduced adhesion to all tested surfaces. For example, adhesion to mica fell from 0.27 ± 0.7 to 0.05 ± 0.01 nN nm-1. The results suggest that polydopamine coatings are suitable to be used for a variety of biomedical applications.

10.
Mol Pharm ; 14(7): 2450-2458, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28570823

RESUMO

Small interfering RNAs (siRNA) have a broad potential as therapeutic agents to reversibly silence any target gene of interest. The clinical application of siRNA requires the use of safe and effective delivery systems. In this study, we investigated the use of nonionic surfactant vesicles (NISV) for the delivery of siRNA. Different types of NISV formulations were synthesized by microfluidic mixing and then evaluated for their physiochemical properties and cytotoxicity. The ability of the NISV to carry and transfect siRNA targeting green fluorescent protein (GFP) into A549 that stably express GFP (copGFP-A549) was evaluated. Flow cytometry and Western blotting were used to study the GFP expression knockdown, and significant knockdown was observed as a result of siRNA delivery to the cells by NISV. This occurred in particular when using Tween 85, which was able to achieve more than 70% GFP knockdown. NISV were thus demonstrated to provide a promising and effective platform for therapeutic delivery of siRNA.


Assuntos
Microfluídica/métodos , RNA Interferente Pequeno/administração & dosagem , Tensoativos/química , Células A549 , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interferência de RNA
11.
Int J Pharm ; 521(1-2): 54-60, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28163227

RESUMO

Non-ionic surfactant vesicles (NISV) are synthetic membrane vesicles formed by self-assembly of a non-ionic surfactant, often in a mixture with cholesterol and a charged chemical species. Different methods can be used to manufacture NISV, with the majority of these requiring bulk mixing of two phases. This mixing process is time-consuming and leads to the preparation of large and highly dispersed vesicles, which affects the consistency of the final product and could hinder subsequent regulatory approval. In this study, we have compared the physical characteristics of NISV prepared using two conventional methods (thin-film hydration method and heating method) with a recently introduced microfluidic method. The resulting particles from these methods were assessed for their physical characteristics and in vitro cytotoxicity. Through microfluidics, nano-sized NISV were prepared in seconds, through rapid and controlled mixing of two miscible phases (lipids dissolved in alcohol and an aqueous medium) in a microchannel, without the need of a size reduction step, as required for the conventional methods. Stability studies over two months showed the particles were stable regardless of the method of preparation and there were no differences in terms of EC50 on A375 and A2780 cell lines. However, this work demonstrates the flexibility and ease of applying lab-on-chip microfluidics for the preparation of NISV that could be used to significantly improve formulation research and development, by enabling the rapid manufacture of a consistent end-product, under controlled conditions.


Assuntos
Química Farmacêutica/métodos , Lipossomos/síntese química , Tensoativos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Lipossomos/farmacologia , Tensoativos/farmacologia
12.
J Biomed Mater Res A ; 105(3): 737-745, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27774773

RESUMO

Using a combination of experimental and computational approaches, the interaction between anastellin, a recombinant fragment of fibronectin, and representative biomaterial surfaces has been examined. Anastellin and superfibronectin have been seen to exhibit antiangiogenic properties and other properties that may make it suitable for consideration for incorporation into biomaterials. The molecular interaction was directly quantified by atomic force microscope (AFM)-based force spectroscopy, complemented by adsorption measurements using quartz crystal microbalance (QCM). Using AFM, it was found that the anastellin molecule facilitates a stronger adhesion on polyurethane films (72.0 pN nm-1 ) than on poly (methyl methacrylate) films (68.6 pN nm-1 ). However, this is not consistent with the QCM adsorption measurements, which show no significant difference. Molecular dynamics simulations of the behavior of anastellin on polyurethane in aqueous solution were performed to rationalize the experimental data, and show that anastellin is capable of rapid adsorption to PU while its secondary structure is stable upon adsorption in water. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 737-745, 2017.


Assuntos
Fibronectinas/química , Membranas Artificiais , Fragmentos de Peptídeos/química , Polimetil Metacrilato/química , Poliuretanos/química , Humanos , Microscopia de Força Atômica , Técnicas de Microbalança de Cristal de Quartzo
13.
Int J Pharm ; 516(1-2): 52-60, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27836752

RESUMO

Non-ionic surfactant vesicles (NISV) are colloidal particles that provide a useful delivery system for drugs and vaccines. One of the methods that is used for NISV preparation is microfluidics in which the lipid components dissolved in organic phase are mixed with an aqueous medium to prepare the particles through self-assembly of the lipids. In this work, we examined the effect of using different types of aqueous media on the characteristics of the NISV prepared by microfluidics. Five aqueous media were tested: phosphate buffered saline, HEPES buffer, Tris buffer, normal saline and distilled water. The resulting particles were tested for their physical characteristics and cytotoxicity. The aqueous media were found to have significant effects on the physical characteristics of the particles, as well as their overall stability under different conditions and their cytotoxicity to different human cell lines. Careful consideration should be taken when choosing the aqueous media for preparing NISV through microfluidics. This is an important factor that will also have implications with respect to the entrapped material, but which in addition may help to design vesicles for different uses based on changing the preparation medium.


Assuntos
Sistemas de Liberação de Medicamentos , Lipídeos/química , Microfluídica/métodos , Tensoativos/química , Linhagem Celular , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Humanos , Testes de Toxicidade
14.
Am J Pharm Educ ; 79(2): 17, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25861098

RESUMO

OBJECTIVE: To examine available data and actions surrounding current pharmacy workforce issues in the United States and United Kingdom. METHODS: Published pharmacy workforce data from the United States and United Kingdom were gathered from various sources, including PUBMED, Internet search engines, and pharmacy organization websites. Data was collated from additional sources including scientific literature, internal documents, news releases, and policy positions. RESULTS: The number of colleges and schools of pharmacy has expanded by approximately 50% in both the United States and United Kingdom over the previous decade. In the United States, continued demand for the pharmacy workforce has been forecasted, but this need is based on outdated supply figures and assumptions for economic recovery. In the United Kingdom, workforce modeling has predicted a significant future oversupply of pharmacists, and action within the profession has attempted to address the situation through educational planning and regulation. CONCLUSION: Workforce planning is an essential task for sustaining a healthy profession. Recent workforce planning mechanisms in the United Kingdom may provide guidance for renewed efforts within the profession in the United States.


Assuntos
Assistência à Saúde , Necessidades e Demandas de Serviços de Saúde , Determinação de Necessidades de Cuidados de Saúde , Assistência Farmacêutica , Farmacêuticos/provisão & distribução , Assistência à Saúde/tendências , Educação em Farmácia , Previsões , Necessidades e Demandas de Serviços de Saúde/tendências , Humanos , Determinação de Necessidades de Cuidados de Saúde/tendências , Assistência Farmacêutica/tendências , Farmacêuticos/tendências , Faculdades de Farmácia , Fatores de Tempo , Reino Unido , Estados Unidos , Recursos Humanos
15.
BMJ Open ; 5(12): e009180, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26719315

RESUMO

OBJECTIVE: This study explored National Health Service (NHS) pharmacists' perceptions and experiences of pharmacist-led research in the workplace. DESIGN: Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis. SETTING: Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority. RESULTS: The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity. CONCLUSIONS: Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pesquisa sobre Serviços de Saúde/normas , Farmacêuticos/psicologia , Papel Profissional , Feminino , Humanos , Entrevistas como Assunto , Masculino , Medicina Estatal , Reino Unido
16.
J Antimicrob Chemother ; 69(3): 835-41, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24176983

RESUMO

OBJECTIVE: To evaluate the association between socioeconomic deprivation and antibiotic prescribing in Scotland. PATIENTS AND METHODS: Data for dispensed antibiotic prescriptions written by general practitioners were obtained for all Scottish National Health Service boards from 2010 to 2012. Deprivation was assessed linking dispensing events to the Scottish Index of Multiple Deprivation (SIMD) score for the patient's datazone (neighbourhood area). The relationship between the deprivation area and antibiotic use (items per 1000 persons per day) was stratified according to the patient's age and sex and the antibiotic class dispensed. A multivariate Poisson regression model was used to formally test the associations. RESULTS: Approximately 12 million prescription items during 2010-2012 were assessed. Patients in the most deprived SIMD quintile had an overall prescription rate that was 36.5% higher than those in the least deprived quintile. The effect of deprivation upon prescription rates was most pronounced for women aged 40-59 years, and for penicillins and metronidazole. CONCLUSIONS: Deprivation was found to have a consistent association with increased rates of antibiotic prescribing in Scotland, which may have significant implications for antimicrobial stewardship and public health campaigns.


Assuntos
Antibacterianos/uso terapêutico , Medicamentos sob Prescrição/uso terapêutico , Prescrições/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Escócia , Fatores Socioeconômicos , Adulto Jovem
17.
Nanomedicine ; 10(5): 971-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24374362

RESUMO

UNLABELLED: Vaccines administered parenterally have been developed against gonadotrophin-releasing hormone (GnRH) for anti-fertility and anti-cancer purposes. The aim of this study was to demonstrate whether mucosal delivery using GnRH immunogens entrapped in lipid nanoparticles (LNP) could induce anti-GnRH antibody titers. Immunogens consisting of KLH (keyhole limpet hemocyanin) conjugated to either GnRH-I or GnRH-III analogues were entrapped in LNP. Loaded non-ionic surfactant vesicles (NISVs) were administered subcutaneously, while nasal delivery was achieved using NISV in xanthan gum and oral delivery using NISV containing deoxycholate (bilosomes). NISV and bilosomes had similar properties: they were spherical, in the nanometre size range, with a slightly negative zeta potential and surface properties that changed with protein loading and inclusion of xanthan gum. Following immunization in female BALB/c mice, systemic antibody responses were similar for both GnRH-I and GnRH-III immunization. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies. FROM THE CLINICAL EDITOR: The main research question addressed in this study was whether mucosal delivery using gonadotrophin-releasing hormone immunogens entrapped in lipid nanoparticles could induce anti-GnRH antibody titers. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies with this approach.


Assuntos
Formação de Anticorpos/imunologia , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/imunologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Administração através da Mucosa , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/imunologia
18.
J Chromatogr A ; 1320: 80-5, 2013 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-24210891

RESUMO

A normal phase high performance liquid chromatography method with evaporative light scattering detection was developed for the simultaneous quantification of the lipid constituents of a non-ionic surfactant vesicle (NIV) delivery system consisting of tetra-ethylene glycol mono n-hexadecyl ether, cholesterol and dicetyl phosphate. An accelerated stability study performed at 25°C/60% relative humidity (RH) and 40°C/75% RH indicated that the NIV were chemically stable. Similar results were observed when stored at 4°C for 469 days. This chromatographic method developed is a sensitive, robust and high throughput analytical technique that offers the potential for rapid quantification of lipids in liposomal and vesicular systems. The results of the chromatographic studies were supported by parallel size and zeta potential measurements.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Sistemas de Liberação de Medicamentos , Luz , Espalhamento de Radiação
19.
Br J Gen Pract ; 63(609): e244-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23540480

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are one of the most common conditions seen in female patients within primary care. Community pharmacists are familiar with symptomatic UTI management and supplying trimethoprim under patient group direction (PGD) for moderate-to-severe uncomplicated UTIs could improve patient access to treatment. AIM: To compare the care pathway of patients with UTI symptoms attending GP services with those receiving management, including trimethoprim supply under PGD, via community pharmacies. DESIGN AND SETTING: Prospective, cross-sectional, mixed methods approach in 10 community pharmacies within NHS Greater Glasgow and Clyde. METHOD: Pharmacies invited a purposive sample of female patients to participate. Pharmacists had the option of supplying trimethoprim under PGD to patients with moderate-to-severe infection meeting the PGD inclusion criteria. Data from patient (questionnaires and semi-structured telephone interviews) and pharmacist (questionnaires and semi-structured, face-to-face interviews) were quantitatively and qualitatively analysed. RESULTS: Data were recorded on 153 patients, 97 presenting with GP prescriptions and 56 presenting directly in the pharmacy with symptoms suggestive of UTI, of whom 41 received trimethoprim via PGD and 15 received symptomatic management. Both GP adherence to local infection management guidelines and pharmacist application of PGD inclusion/exclusion criteria required improvement. There was demand and support, from patients and pharmacists, for access to antibiotic treatments for UTIs, without prescription, through community pharmacies. CONCLUSION: Operating within PGD controls, antibiotic treatments for UTIs could be provided via community pharmacy to improve patient access to treatment which may also maintain antibiotic stewardship and reduce GP workload.


Assuntos
Anti-Infecciosos Urinários/uso terapêutico , Serviços Comunitários de Farmácia , Medicina Geral , Trimetoprima/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Escócia/epidemiologia , Inquéritos e Questionários , Infecções Urinárias/epidemiologia
20.
Expert Rev Vaccines ; 11(9): 1139-55, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23151169

RESUMO

In general, there are only a few vaccines administered via mucosal routes, as the mucosal immune system presents numerous hurdles, including diversity in mucosal surface structure, complexity in immune cell interaction and limitations in experimental methodology. This therefore necessitates a range of strategies to be used for each target area. With reference to the three main routes of delivery and associated mucosal surfaces (oral/intestinal, nasal/respiratory and female genital tract), this review examines how coadministration of immune-stimulatory molecules, adjuvants, delivery systems and mucoadhesives are used to improve mucosal vaccine efficacy. Key considerations to the development of next-generation mucosal vaccines include improved efficacy and safety, technological advancements in medical devices to enable convenience and better administration, as well as reduced manufacturing costs.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Administração através da Mucosa , Vacinas/administração & dosagem , Vacinas/imunologia , Animais , Humanos , Imunidade nas Mucosas
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