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1.
J Wound Care ; 33(Sup4a): cxxx-cxxxix, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38588059

RESUMO

OBJECTIVE: To determine whether person-centred music (PCMusic) contributes to reducing pain during painful leg ulcer dressing change procedures indicated by: decreased levels of indicators related to stress; decreased pain scores; and a more favourable treatment climate during the dressing change procedure. METHOD: A case study of a 51-year-old female patient with chronic inherited disease weakening her connective tissues. Quantitative data entailed temporal measurements of stress indicators including: heart pulse rate; oxygen saturation (SpO2); saliva cortisol; and a visual analogue scale (VAS). Qualitative data comprised phenomenological treatment descriptions and patient/licensed practical nurse (LPN) questionnaires. RESULTS: The patient's body temperature remained steady throughout all treatments. Blood pressure was excluded due to missing data. No significant pulse rate differences in relation to music/no music could be observed during treatment. Comparing PCMusic to the patient's own other music (POOM), the pulse rate was greater in both magnitude and variation when the patient listened to POOM. Oxygen saturation showed no significant difference between PCMusic and music/no music. No significant difference was observed pre-/post-debridement with music. Similarly, no significant difference was observed pre-/post-debridement with no music. Treatment with no music showed the highest VAS score; PCMusic treatments had the lowest scores. Qualitative data showed that both patient and LPNs found that PCMusic decreased pain during dressing change. CONCLUSION: The results of this case study indicate that PCMusic is a suitable complementary treatment to decrease patient pain. Patients' general health status is important when using quantitative stress/pain marker measurements. For cohort selection in future studies, we suggest healthy patients undergoing slightly painful or unpleasant treatments, patients in postoperative care and obstetric care.


Assuntos
Úlcera da Perna , Música , Feminino , Humanos , Pessoa de Meia-Idade , Bandagens , Doença Crônica , Dor
2.
J Wound Care ; 30(7): 534-542, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34256595

RESUMO

Objective: The prevalence and economic burden of wounds are growing. Any wound has the potential to become hard-to-heal and require frequent care. Clinicians need to find ways to absorb demand on services without compromising outcomes. Drivers of wound care efficiency-time-to-heal, frequency of dressing change and the incidence of complications-can be evaluated to shape future wound management. A survey of wound care was conducted by clinicians from five centres in Sweden over a one-week period, during which clinicians documented every wound once. At the time of surveying, 49% of wounds were considered to be improving, infection incidence was 11.7% and dressings were changed a mean of 2.2 times per week, with highly exuding wounds changed 6.9 times per week. The data highlighted the importance of diagnosing patient and wound characteristics in selecting treatments and organising care. Recognised gaps in diagnoses potentially identify opportunities to influence healing, complication incidence and intensity of nursing, thus reducing demand on resources. In conclusion, this survey highlights opportunities to reduce the burdens these drivers present. Through improved diagnosis and alignment to recognised care pathways, there is potential to improve patient outcomes and alleviate the strains placed upon wound care providers.


Assuntos
Bandagens , Cicatrização , Humanos , Infecção da Ferida Cirúrgica , Suécia/epidemiologia
3.
Methods Mol Biol ; 2262: 233-250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977480

RESUMO

On the plasma membrane, Ras is organized into laterally segregated proteo-lipid complexes called nanoclusters. The extent of Ras nanoclustering correlates with its signaling output, positioning nanocluster as dynamic signaling gain modulators. Recent evidence suggests that stacked dimers of Ras and Raf are elemental units at least of one type of Ras nanocluster. However, it is still incompletely understood, in which physiological contexts nanoclustering is regulated and which constituents are parts of nanocluster. Nonetheless, disruption of nanoclustering faithfully diminishes Ras activity in cells, suggesting Ras nanocluster as potential drug targets.While there are several methods available to study Ras nanocluster , fluorescence or Förster resonance energy transfer (FRET ) between fluorescently labeled, nanoclustered Ras proteins is a relatively simple readout. FRET measurements using fluorescence lifetime imaging microscopy (FLIM ) have proven to be robust and sensitive to determine Ras nanoclustering changes. Loss of FRET that emerges due to nanoclustering reports on all processes upstream of Ras nanoclustering, i.e., also on proper trafficking or lipid modification of Ras. Here we report our standard FLIM-FRET protocol to measure nanoclustering-dependent FRET of Ras in mammalian cells. Importantly, nanoclustering-dependent FRET is one of the few methods that can detect differences between the Ras isoforms.


Assuntos
Membrana Celular/metabolismo , Transferência Ressonante de Energia de Fluorescência/métodos , Processamento de Imagem Assistida por Computador/métodos , Lipídeos de Membrana/metabolismo , Microscopia de Fluorescência/métodos , Nanopartículas/química , Proteínas ras/metabolismo , Membrana Celular/ultraestrutura , Humanos , Transdução de Sinais
4.
Cancers (Basel) ; 13(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672199

RESUMO

The ATP-competitive inhibitors of Hsp90 have been tested predominantly in kinase addicted cancers; however, they have had limited success. A mechanistic connection between Hsp90 and oncogenic K-Ras is not known. Here, we show that K-Ras selectivity is enabled by the loss of the K-Ras membrane nanocluster modulator galectin-3 downstream of the Hsp90 client HIF-1α. This mechanism suggests a higher drug sensitivity in the context of KRAS mutant, HIF-1α-high and/or Gal3-high cancer cells, such as those found, in particular, in pancreatic adenocarcinoma. The low toxicity of conglobatin further indicates a beneficial on-target toxicity profile for Hsp90/Cdc37 interface inhibitors. We therefore computationally screened >7 M compounds, and identified four novel small molecules with activities of 4 µM-44 µM in vitro. All of the compounds were K-Ras selective, and potently decreased the Hsp90 client protein levels without inducing the heat shock response. Moreover, they all inhibited the 2D proliferation of breast, pancreatic, and lung cancer cell lines. The most active compounds from each scaffold, furthermore, significantly blocked 3D spheroids and the growth of K-Ras-dependent microtumors. We foresee new opportunities for improved Hsp90/Cdc37 interface inhibitors in cancer and other aging-associated diseases.

5.
Sci Rep ; 7(1): 8944, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28827765

RESUMO

As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator. We show that modulation of the SREBP1 levels downstream of S6K1 has opposite effects on oncogenic H-ras and K-ras nanoscale membrane organisation, ensuing signalling output and promotion of mammospheres expressing these oncogenes. Our data suggest that modulation of phosphatidic acid, a major target of SREBP1 controlled lipid metabolism, is sufficient to affect H-ras and K-ras oppositely in the membrane. Thus mTORC1 activation increases H-ras-, but decreases K-ras-signalling output in cells transformed with the respective oncogene. Given the different impact of these two Ras isoforms on stemness, our results could have implications for stem cell biology and inhibition of cancer stem cells.


Assuntos
Retroalimentação Fisiológica , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Linhagem Celular Tumoral , Células HEK293 , Humanos , Metabolismo dos Lipídeos , Células-Tronco Neoplásicas/metabolismo , Ácidos Fosfatídicos/metabolismo , Transdução de Sinais
6.
Oncotarget ; 8(27): 44550-44566, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28562352

RESUMO

Currently several combination treatments of mTor- and Ras-pathway inhibitors are being tested in cancer therapy. While multiple feedback loops render these central signaling pathways robust, they complicate drug targeting.Here, we describe a novel H-ras specific feedback, which leads to an inadvertent rapalog induced activation of tumorigenicity in Ras transformed cells. We find that rapalogs specifically increase nanoscale clustering (nanoclustering) of oncogenic H-ras but not K-ras on the plasma membrane. This increases H-ras signaling output, promotes mammosphere numbers in a H-ras-dependent manner and tumor growth in ovo. Surprisingly, also other FKBP12 binders, but not mTor-inhibitors, robustly decrease FKBP12 levels after prolonged (>2 days) exposure. This leads to an upregulation of the nanocluster scaffold galectin-1 (Gal-1), which is responsible for the rapamycin-induced increase in H-ras nanoclustering and signaling output. We provide evidence that Gal-1 promotes stemness features in tumorigenic cells. Therefore, it may be necessary to block inadvertent induction of stemness traits in H-ras transformed cells by specific Gal-1 inhibitors that abrogate its effect on H-ras nanocluster. On a more general level, our findings may add an important mechanistic explanation to the pleiotropic physiological effects that are observed with rapalogs.


Assuntos
Autorrenovação Celular/genética , Galectina 1/genética , Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas ras/genética , Animais , Carcinogênese , Linhagem Celular Tumoral , Galectina 1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Neoplasias/metabolismo , Neoplasias/patologia , Ligação Proteica , Esferoides Celulares , Proteína 1A de Ligação a Tacrolimo/genética , Proteína 1A de Ligação a Tacrolimo/metabolismo , Células Tumorais Cultivadas , Proteínas ras/metabolismo
7.
PLoS One ; 11(7): e0159677, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27437940

RESUMO

Ras-induced senescence mediated through ASPP2 represents a barrier to tumour formation. It is initiated by ASPP2's interaction with Ras at the plasma membrane, which stimulates the Raf/MEK/ERK signaling cascade. Ras to Raf signalling requires Ras to be organized in nanoscale signalling complexes, called nanocluster. We therefore wanted to investigate whether ASPP2 affects Ras nanoclustering. Here we show that ASPP2 increases the nanoscale clustering of all oncogenic Ras isoforms, H-ras, K-ras and N-ras. Structure-function analysis with ASPP2 truncation mutants suggests that the nanocluster scaffolding activity of ASPP2 converges on its α-helical domain. While ASPP2 increased effector recruitment and stimulated ERK and AKT phosphorylation, it did not increase colony formation of RasG12V transformed NIH/3T3 cells. By contrast, ASPP2 was able to suppress the transformation enhancing ability of the nanocluster scaffold Gal-1, by competing with the specific effect of Gal-1 on H-rasG12V- and K-rasG12V-nanoclustering, thus imposing ASPP2's ERK and AKT signalling signature. Similarly, ASPP2 robustly induced senescence and strongly abrogated mammosphere formation irrespective of whether it was expressed alone or together with Gal-1, which by itself showed the opposite effect in Ras wt or H-ras mutant breast cancer cells. Our results suggest that Gal-1 and ASPP2 functionally compete in nanocluster for active Ras on the plasma membrane. ASPP2 dominates the biological outcome, thus switching from a Gal-1 supported growth-promoting setting to a senescence inducing and stemness suppressive program in cancer cells. Our results support Ras nanocluster as major integrators of tumour fate decision events.


Assuntos
Neoplasias/genética , Proteína Oncogênica v-akt/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Supressoras de Tumor/genética , Proteínas ras/genética , Animais , Apoptose/genética , Carcinogênese/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Transformação Celular Neoplásica/genética , Senescência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases/genética , Células MCF-7 , Camundongos , Células NIH 3T3 , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Tecidos Suporte , Proteínas Supressoras de Tumor/biossíntese , Quinases raf/genética , Quinases raf/metabolismo , Proteínas ras/metabolismo
8.
Int Wound J ; 13 Suppl 2: 5-15, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27460943

RESUMO

Treatment of wounds of different aetiologies constitutes a major part of the total health care budget. It is estimated that 1·5-2 million people in Europe suffer from acute or chronic wounds. These wounds are managed both in hospitals and in community care. The patients suffering from these wounds report physical, mental and social consequences of their wounds and the care of them. It is often believed that the use of wound dressings per se is the major cost driver in wound management, whereas in fact, nursing time and hospital costs are together responsible for around 80-85% of the total cost. Healing time, frequency of dressing change and complications are three important cost drivers. However, with the use of modern, advanced technology for more rapid wound healing, all these cost drivers can be substantially reduced. A basic understanding of the terminology and principles of Health Economics in relation to wound management might therefore be of interest.


Assuntos
Úlcera Cutânea/terapia , Ferimentos e Lesões/terapia , Bandagens , Análise Custo-Benefício , Custos de Cuidados de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Avaliação de Resultados em Cuidados de Saúde , Úlcera Cutânea/economia , Úlcera Cutânea/epidemiologia , Cicatrização , Ferimentos e Lesões/economia , Ferimentos e Lesões/epidemiologia
9.
Curr Microbiol ; 73(4): 463-73, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27324340

RESUMO

In the global perspective of antibiotic resistance, it is urgent to find potent topical antibiotics for the use in human and animal infection. Healing of equine wounds, particularly in the limbs, is difficult due to hydrostatic factors and exposure to environmental contaminants, which can lead to heavy bio-burden/biofilm formation and sometimes to infection. Therefore, antibiotics are often prescribed. Recent studies have shown that honeybee-specific lactic acid bacteria (LAB), involved in honey production, and inhibit human wound pathogens. The aim of this pilot study was to investigate the effects on the healing of hard-to-heal equine wounds after treatment with these LAB symbionts viable in a heather honey formulation. For this, we included ten horses with wound duration of >1 year, investigated the wound microbiota, and treated wounds with the novel honeybee LAB formulation. We identified the microbiota using MALDI-TOF mass spectrometry and DNA sequencing. In addition, the antimicrobial properties of the honeybee LAB formulation were tested against all wound isolates in vitro. Our results indicate a diverse wound microbiota including fifty-three bacterial species that showed 90 % colonization by at least one species of Staphylococcus. Treatment with the formulation promoted wound healing in all cases already after the first application and the wounds were either completely healed (n = 3) in less than 20 days or healing was in progress. Furthermore, the honeybee LAB formulation inhibited all pathogens when tested in vitro. Consequently, this new treatment option presents as a powerful candidate for the topical treatment of hard-to-heal wounds in horses.


Assuntos
Abelhas/microbiologia , Terapia Biológica , Mel/microbiologia , Doenças dos Cavalos/terapia , Infecções Estafilocócicas/veterinária , Staphylococcus/efeitos dos fármacos , Ferimentos e Lesões/veterinária , Animais , Bifidobacterium/metabolismo , Mel/análise , Mel/estatística & dados numéricos , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/fisiopatologia , Cavalos , Ácido Láctico/metabolismo , Lactobacillus/metabolismo , Projetos Piloto , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/fisiopatologia , Infecções Estafilocócicas/terapia , Staphylococcus/genética , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/isolamento & purificação , Cicatrização , Ferimentos e Lesões/microbiologia , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
10.
Nurse Educ Pract ; 17: 102-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26776502

RESUMO

The World Health Organization and the International Council of Nurses recognises the importance of nurses' involvement in disaster preparedness and response. The aim of this study was to describe and compare self-reported disaster nursing competence (DNC) among nursing students (NSs) and among registered nurses (RNs) with professional experience. Further to investigate possible associations between self-reported DNC and background factors. A cross-sectional study was conducted of 569 NSs and 227 RNs. All respondents completed the 88-item Nurse Professional Competence Scale, including three items assessing DNC. Significant differences were found among the NSs depending on which University/University College they had attended. RNs reported significantly higher overall DNC and better ability to handle situations involving violence, and to apply principles of disaster medicine during serious events. RNs working in emergency care reported significantly better DNC ability, compared with RNs working in other areas of healthcare. Multiple linear regression analysis showed that working night shift and working in emergency care were positively associated with high self-reported overall DNC. The results indicate that workplace experience of serious events increase the readiness of registered nurses to handle violence, to act in accordance with safety regulations, and to apply principles of disaster medicine during serious events.


Assuntos
Planejamento em Desastres/organização & administração , Enfermeiras e Enfermeiros , Competência Profissional , Autorrelato , Estudantes de Enfermagem , Violência , Atitude do Pessoal de Saúde , Estudos Transversais , Serviços Médicos de Emergência , Humanos , Suécia
11.
Nurse Educ Today ; 37: 178-83, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26703792

RESUMO

BACKGROUND: Nursing competence is of significant importance for patient care. Newly graduated nursing students rate their competence as high. However, the impact of different designs of nursing curricula on nursing students' self-reported nursing competence areas is seldom reported. OBJECTIVES: To compare newly graduated nursing students' self-reported professional competence before and after the implementation of a new nursing curriculum. The study had a descriptive comparative design. Nursing students, who graduated in 2011, having studied according to an older curriculum, were compared with those who graduated in 2014, after a new nursing curriculum with more focus on person-centered nursing had been implemented. SETTING: A higher education nursing program at a Swedish university. PARTICIPANTS: In total, 119 (2011 n=69, 2014 n=50) nursing students responded. METHODS: Nursing students' self-reported professional competencies were assessed with the Nurse Professional Competence (NPC) scale. RESULTS: There were no significant differences between the two groups of nursing students, who graduated in 2011 and 2014, respectively, with regard to age, sex, education, or work experience. Both groups rated their competencies as very high. Competence in value-based nursing was perceived to be significantly higher after the change in curriculum. The lowest competence, both in 2011 and 2014, was reported in education and supervision of staff and students. CONCLUSIONS: Our findings indicate that newly graduated nursing students - both those following the old curriculum and the first batch of students following the new one - perceive that their professional competence is high. Competence in value-based nursing, measured with the NPC scale, was reported higher after the implementation of a new curriculum, reflecting curriculum changes with more focus on person-centered nursing.


Assuntos
Competência Clínica , Currículo , Necessidades e Demandas de Serviços de Saúde , Autorrelato , Estudantes de Enfermagem , Adulto , Bacharelado em Enfermagem , Feminino , Humanos , Masculino , Suécia
12.
J Lab Autom ; 21(2): 238-45, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26384400

RESUMO

Fluorescence resonance energy transfer (FRET) is widely used to study conformational changes of macromolecules and protein-protein, protein-nucleic acid, and protein-small molecule interactions. FRET biosensors can serve as valuable secondary assays in drug discovery and for target validation in mammalian cells. Fluorescence lifetime imaging microscopy (FLIM) allows precise quantification of the FRET efficiency in intact cells, as FLIM is independent of fluorophore concentration, detection efficiency, and fluorescence intensity. We have developed an automated FLIM system using a commercial frequency domain FLIM attachment (Lambert Instruments) for wide-field imaging. Our automated FLIM system is capable of imaging and analyzing up to 50 different positions of a slide in less than 4 min, or the inner 60 wells of a 96-well plate in less than 20 min. Automation is achieved using a motorized stage and controller (Prior Scientific) coupled with a Zeiss Axio Observer body and full integration into the Lambert Instruments FLIM acquisition software. As an application example, we analyze the interaction of the oncoprotein Ras and its effector Raf after drug treatment. In conclusion, our automated FLIM imaging system requires only commercial components and may therefore allow for a broader use of this technique in chemogenomics projects.


Assuntos
Automação Laboratorial/métodos , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Mapeamento de Interação de Proteínas/métodos , Transferência Ressonante de Energia de Fluorescência , Ensaios de Triagem em Larga Escala , Quinases raf/metabolismo , Proteínas ras/metabolismo
13.
Nat Prod Res ; 30(5): 622-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25898918

RESUMO

The wound-healing properties of Plantago major L. (plantain) were evaluated using an ex-vivo porcine wound-healing model. Ethanol- and water-based extracts were prepared from greenhouse-grown and freeze-dried leaves of P. major. Both types of extracts stimulated wound healing in porcine skin, but the ethanol-based extracts had a somewhat stronger effect. A concentration of 1.0 mg/mL (on dry weight basis) produced the best results for both types of extracts.


Assuntos
Medicina Tradicional , Extratos Vegetais/farmacologia , Plantago/química , Cicatrização/efeitos dos fármacos , Animais , Etanol , Liofilização , Folhas de Planta/química , Polifenóis/química , Polifenóis/farmacologia , Pele/patologia , Solventes , Suínos , Água
14.
Nurse Educ Today ; 36: 165-71, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26586256

RESUMO

BACKGROUND: International organisations, e.g. WHO, stress the importance of competent registered nurses (RN) for the safety and quality of healthcare systems. Low competence among RNs has been shown to increase the morbidity and mortality of inpatients. OBJECTIVES: To investigate self-reported competence among nursing students on the point of graduation (NSPGs), using the Nurse Professional Competence (NPC) Scale, and to relate the findings to background factors. METHODS AND PARTICIPANTS: The NPC Scale consists of 88 items within eight competence areas (CAs) and two overarching themes. Questions about socio-economic background and perceived overall quality of the degree programme were added. In total, 1086 NSPGs (mean age, 28.1 [20-56]years, 87.3% women) from 11 universities/university colleges participated. RESULTS: NSPGs reported significantly higher scores for Theme I "Patient-Related Nursing" than for Theme II "Organisation and Development of Nursing Care". Younger NSPGs (20-27years) reported significantly higher scores for the CAs "Medical and Technical Care" and "Documentation and Information Technology". Female NSPGs scored significantly higher for "Value-Based Nursing". Those who had taken the nursing care programme at upper secondary school before the Bachelor of Science in Nursing (BSN) programme scored significantly higher on "Nursing Care", "Medical and Technical Care", "Teaching/Learning and Support", "Legislation in Nursing and Safety Planning" and on Theme I. Working extra paid hours in healthcare alongside the BSN programme contributed to significantly higher self-reported scores for four CAs and both themes. Clinical courses within the BSN programme contributed to perceived competence to a significantly higher degree than theoretical courses (93.2% vs 87.5% of NSPGs). SUMMARY AND CONCLUSION: Mean scores reported by NSPGs were highest for the four CAs connected with patient-related nursing and lowest for CAs relating to organisation and development of nursing care. We conclude that the NPC Scale can be used to identify and measure aspects of self-reported competence among NSPGs.


Assuntos
Competência Profissional , Estudantes de Enfermagem/psicologia , Adulto , Educação em Enfermagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Int Wound J ; 13(5): 668-79, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25195876

RESUMO

Could honeybees' most valuable contribution to mankind besides pollination services be alternative tools against infections? Today, due to the emerging antibiotic-resistant pathogens, we are facing a new era of searching for alternative tools against infections. Natural products such as honey have been applied against human's infections for millennia without sufficient scientific evidence. A unique lactic acid bacterial (LAB) microbiota was discovered by us, which is in symbiosis with honeybees and present in large amounts in fresh honey across the world. This work investigates if the LAB symbionts are the source to the unknown factors contributing to honey's properties. Hence, we tested the LAB against severe wound pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and vancomycin-resistant Enterococcus (VRE) among others. We demonstrate a strong antimicrobial activity from each symbiont and a synergistic effect, which counteracted all the tested pathogens. The mechanisms of action are partly shown by elucidating the production of active compounds such as proteins, fatty acids, anaesthetics, organic acids, volatiles and hydrogen peroxide. We show that the symbionts produce a myriad of active compounds that remain in variable amounts in mature honey. Further studies are now required to investigate if these symbionts have a potential in clinical applications as alternative tools against topical human and animal infections.


Assuntos
Mel , Animais , Antibacterianos , Anti-Infecciosos , Abelhas , Ácido Láctico , Lactobacillales , Staphylococcus aureus Resistente à Meticilina
16.
Int Wound J ; 13(5): 729-37, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25196349

RESUMO

Treatment and management of chronic wounds is a large burden on the health sector and causes substantial suffering for the patients. We believe that 13 lactic acid bacteria (LAB) symbionts isolated from the honey crop of the honeybee are important players in the antimicrobial action of honey, by producing antimicrobial substances and can be used in combination with heather honey as an effective treatment in wound management. A total of 22 patients with chronic ulcers were included; culture-dependent and molecular-based (MALDI-MS and 16S rRNA gene sequencing) techniques were used to identify bacteria from chronic wounds. These clinical isolates were used for in vitro antimicrobial testing with standardised viable LAB and sterilised heather honey mixture. Twenty of the patients' wounds were polymicrobial and 42 different species were isolated. Patient isolates that were tested in vitro were inhibited by the LAB and honey combination with inhibitory zones comparable with different antibiotics. LAB and heather honey in combination presents a new topical option in chronic wound management because of the healing properties of honey, antimicrobial metabolite production from the LAB and their bactericidal effect on common chronic wound pathogens. This new treatment may be a stepping stone towards an alternative solution to antibiotics.


Assuntos
Antibiose , Bactérias , Abelhas/microbiologia , Terapia Biológica , Mel/microbiologia , Úlcera Varicosa/terapia , Ferimentos e Lesões/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Infecciosos/uso terapêutico , Doença Crônica/terapia , Feminino , Humanos , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Simbiose , Cicatrização/fisiologia , Ferimentos e Lesões/microbiologia
17.
BMC Public Health ; 14: 1247, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25476556

RESUMO

BACKGROUND: The incidence of disability pension (DP) is high in several European countries. However, knowledge on associations of cause-specific DP and premature death is limited. The aims were to: 1) investigate the association between cause-specific DP and all-cause and cause-specific mortality among women and men and 2) examine period effects of this association. METHODS: Three prospective population-based cohort studies were conducted, the first including all individuals aged 16-64 years who lived in Sweden all of 1995 and who were not on DP before 1995 (N = 5,006,523, 48.8% women). Those granted DP in 1995 were compared to those not granted DP regarding mortality during 1996-2009. Two other cohorts were created in a similar fashion, for 2000 and 2005, respectively, and in comparisons each of the three cohorts were followed up for four years with regard to all-cause mortality as well as death due to cancer, circulatory disorders, or suicide. All analyses were stratified by sex and we controlled for a number of socio-demographic factors and inpatient care. RESULTS: Individuals with granted DP had a higher mortality risk, women (HR 1.75; 95% CI 1.68-1.82) and men (HR 1.66; 95% CI 1.61-1.71) and highest for cancer. People on DP with some diagnoses had higher risk of premature death in other causes of death than their DP diagnoses. All-cause mortality risk varied with DP-diagnosis and was lowest for musculoskeletal diagnoses. The mortality HR decreased among women with DP between the cohort 1995, HR 2.07 (1.92-2.24) and the cohort 2005, 1.84 (1.71-1.99). Here, temporal decreases in mortality risk occurred particularly in DP due to mental diagnoses and cancer. CONCLUSIONS: All DP diagnoses were associated with a higher mortality risk. Even individuals granted DP due to diagnoses with low mortality risk displayed a higher risk for premature death. This warrants close monitoring of disability pensioners and further studies on consequences of being on disability pension.


Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Mortalidade Prematura , Mortalidade/tendências , Pensões/estatística & dados numéricos , Adulto , Idoso , Causas de Morte , Estudos de Coortes , Demografia , Feminino , Humanos , Incidência , Masculino , Transtornos Mentais/mortalidade , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/mortalidade , Estudos Prospectivos , Fatores de Risco , Suicídio/estatística & dados numéricos , Suécia/epidemiologia
18.
Eur J Med Chem ; 84: 77-89, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25016230

RESUMO

Phosphonocarboxylate (PC) analogs of the anti-osteoporotic drugs, bisphosphonates, represent the first class of selective inhibitors of Rab geranylgeranyl transferase (RabGGTase, RGGT), an enzyme implicated in several diseases including ovarian, breast and skin cancer. Here we present the synthesis and biological characterization of an extended set of this class of compounds, including lipophilic derivatives of the known RGGT inhibitors. From this new panel of PCs, we have identified an inhibitor of RGGT that is of similar potency as the most active published phosphonocarboxylate, but of higher selectivity towards this enzyme compared to prenyl pyrophosphate synthases. New insights into structural requirements are also presented, showing that only PC analogs of the most potent 3rd generation bisphosphonates inhibit RGGT. In addition, the first phosphonocarboxylate-derived GGPPS inhibitor is reported.


Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Organofosfonatos/farmacologia , Alquil e Aril Transferases/metabolismo , Animais , Bovinos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células HeLa , Humanos , Estrutura Molecular , Organofosfonatos/síntese química , Organofosfonatos/química , Relação Estrutura-Atividade
19.
BMC Public Health ; 14: 733, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-25037232

RESUMO

BACKGROUND: As the number of studies on the future situation of sickness absentees still is very limited, we aimed to investigate the association between number of sick-leave days and future all-cause and cause-specific mortality among women and men. METHODS: A cohort of 2 275 987 women and 2 393 248 men, aged 20-64 years in 1995 was followed 1996-2006 with regard to mortality. Data were obtained from linked authority-administered registers. The relative risks (RR) and 95% confidence intervals (CI) of mortality with and without a 2-year wash-out period were estimated by multivariate Poisson regression analyses. All analyses were stratified by sex, adjusting for socio demographics and inpatient care. RESULTS: A gradually higher all-cause mortality risk occurred with increasing number of sick-leave days in 1995, among both women (RR 1.11; CI 1.07-1.15 for those with 1-15 sick-leave days to RR 2.45; CI 2.36-2.53 among those with 166-365 days) and men (RR 1.20; CI 1.17-1.24 to RR 1.91; CI 1.85-1.97). Multivariate risk estimates were comparable for the different causes of death (circulatory disease, cancer, and suicide). The two-year washout period had only a minor effect on the risk estimates. CONCLUSION: Even a low number of sick-leave days was associated with a higher risk for premature death in the following 11 years, also when adjusting for morbidity. This was the case for both women and men and also for cause-specific mortality. More knowledge is warranted on the mechanisms leading to higher mortality risks among sickness absentees, as sickness certification is a common measure in health care, and most sick leave is due to diagnoses you do not die from.


Assuntos
Causas de Morte/tendências , Mortalidade , Licença Médica/estatística & dados numéricos , Absenteísmo , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Suécia/epidemiologia
20.
Int Wound J ; 11(4): 416-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23521782

RESUMO

Early detection of non blanching erythema (pressure ulcer category I) is necessary to prevent any further skin damage. An objective method to discriminate between blanching/non blanching erythema is presently not available. The purpose of this investigation was to explore if a non invasive objective method could differentiate between blanching/non blanching erythema in the sacral area of patients undergoing hip fracture surgery. Seventy-eight patients were included. The sacral area of all patients was assessed using (i) conventional finger-press test and (ii) digital reading of the erythema index assessed with reflectance spectrophotometry. The patients were examined at admission and during 5 days postsurgery. Reflectance spectrophotometry measurements proved able to discriminate between blanching/non blanching erythema. The reliability, quantified by the intra-class correlation coefficient, was excellent between repeated measurements over the measurement period, varying between 0·82 and 0·96, and a significant change was recorded in the areas from day 1 to day 5 (P < 0·0001). The value from the reference point did not show any significant changes over the same period (P = 0·32). An objective method proven to identify early pressure damage to tissue can be a valuable tool in clinical practice.


Assuntos
Eritema/diagnóstico , Lesão por Pressão/complicações , Pele/patologia , Espectrofotometria/métodos , Idoso , Diagnóstico Precoce , Eritema/etiologia , Feminino , Seguimentos , Humanos , Masculino , Lesão por Pressão/congênito , Lesão por Pressão/diagnóstico , Lesão por Pressão/prevenção & controle , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Sacro
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