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1.
Scand J Occup Ther ; 30(5): 616-627, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34846249

RESUMEN

BACKGROUND: Support from significant others is important for participation in everyday life for persons with rheumatoid arthritis (RA). Meanwhile, significant others also experience limitations. AIMS: To explore how support is expressed by persons with RA and significant others, and how support relates to participation in everyday life of persons with RA. MATERIAL AND METHODS: Sixteen persons with RA and their significant others participated in individual semi-structured interviews. The material was analyzed using dyadic analysis. RESULTS: Persons with RA and significant others reported that RA and support had become natural parts of everyday life, especially emotional support. The reciprocal dynamics of support were also expressed as imperative. Also, support from people outside of the dyads and well-functioning communication facilitated everyday life. CONCLUSIONS: Significant others and the support they give are prominent factors and facilitators in everyday life of persons with RA. Concurrently, the support persons with RA provide is important, along with support from outside of the dyads. SIGNIFICANCE: The results indicate that the interaction between persons with RA and the social environment is central to gain insight into how support should be provided for optimal participation in everyday life. Significant others can preferably be more involved in the rehabilitation process.


Asunto(s)
Actividades Cotidianas , Artritis Reumatoide , Apoyo Social , Artritis Reumatoide/psicología , Artritis Reumatoide/rehabilitación , Humanos , Emociones , Medio Social , Investigación Cualitativa , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Participación del Paciente/psicología , Calidad de Vida
2.
Int J Food Sci Nutr ; 73(8): 1080-1090, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35930435

RESUMEN

It has not been clarified whether the anti-atherosclerotic effect of lingonberry can be ascribed to its content of flavonoids or dietary fibre or both. The aim of this study was to evaluate the metabolic effects of whole lingonberries compared with isolated flavonoid and fibre fractions on atherosclerotic plaques, plasma lipid profiles, gut microbiota and microbiota-dependent metabolites in an Apoe-/- mouse model. Mice fed whole lingonberries showed the lowest amount of atherosclerotic plaques, while mice fed the fibre fraction had the highest formation of caecal butyric acid. Flavonoids, rather than dietary fibre, were suggested to be the components that favour proliferation of Akkermansia, as judged by the lowest abundance of this bacterium in mice fed the fibre fraction. All groups fed lingonberry diets had both, lower Firmicutes/Bacteroidetes ratios and creatinine concentrations, compared with the control. To conclude, different components in lingonberries are associated with different physiological effects in Apoe-/- mice.


Asunto(s)
Microbioma Gastrointestinal , Placa Aterosclerótica , Vaccinium vitis-Idaea , Ratones , Animales , Vaccinium vitis-Idaea/metabolismo , Flavonoides/farmacología , Fibras de la Dieta/metabolismo , Apolipoproteínas E/genética
3.
Nutrients ; 14(5)2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35267913

RESUMEN

The health benefits of bean consumption are widely recognized and are largely attributed to the dietary fiber content. This study investigated and compared the effects of whole brown beans and an isolated bean dietary fiber fraction on the plasma lipid profile, atherosclerotic plaque amount, gut microbiota, and microbiota-dependent metabolites (cecal short-chain fatty acids (SCFAs) and plasma methylamines) in Apoe-/- mice fed high fat diets for 10.5 weeks. The results showed that both whole bean and the isolated fiber fraction had a tendency to lower atherosclerotic plaque amount, but not plasma lipid concentration. The whole bean diet led to a significantly higher diversity of gut microbiota compared with the high fat diet. Both bean diets resulted in a lower Firmicutes/Bacteroidetes ratio, higher relative abundance of unclassified S24-7, Prevotella, Bifidobacterium, and unclassified Clostridiales, and lower abundance of Lactobacillus. Both bean diets resulted in higher formation of all cecal SCFAs (higher proportion of propionic acid and lower proportion of acetic acid) and higher plasma trimethylamine N-oxide concentrations compared with the high fat diet. Whole beans and the isolated fiber fraction exerted similar positive effects on atherosclerotic plaque amount, gut microbiota, and cecal SCFAs in Apoe-/- mice compared with the control diets.


Asunto(s)
Aterosclerosis , Microbioma Gastrointestinal , Microbiota , Phaseolus , Animales , Apolipoproteínas E/genética , Aterosclerosis/microbiología , Dieta Alta en Grasa , Fibras de la Dieta/farmacología , Ratones
4.
Anal Bioanal Chem ; 413(21): 5349-5360, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34258650

RESUMEN

Trimethylamine-N-oxide (TMAO), a microbiome-derived metabolite from the metabolism of choline, betaine, and carnitines, is associated to adverse cardiovascular outcomes. A method suitable for routine quantification of TMAO and its precursors (trimethylamine (TMA), choline, betaine, creatinine, and propionyl-, acetyl-, and L-carnitine) in clinical and food samples has been developed based on LC-MS. TMA was successfully derivatized using iodoacetonitrile, and no cross-reactions with TMAO or the other methylamines were detected. Extraction from clinical samples (plasma and urine) was performed after protein precipitation using acetonitrile:methanol. For food samples (meatballs and eggs), water extraction was shown to be sufficient, but acid hydrolysis was required to release bound choline before extraction. Baseline separation of the methylamines was achieved using a neutral HILIC column and a mobile phase consisting of 25 mmol/L ammonium formate in water:ACN (30:70). Quantification was performed by MS using external calibration and isotopic labelled internal standards. The assay proved suitable for both clinical and food samples and was linear from ≈ 0.1 up to 200 µmol/L for all methylamines except for TMA and TMAO, which were linear up to 100 µmol/L. Recoveries were 91-107% in clinical samples and 76-98% in food samples. The interday (n=8, four duplicate analysis) CVs were below 9% for all metabolites in clinical and food samples. The method was applied successfully to determine the methylamine concentrations in plasma and urine from the subjects participating in an intervention trial (n=10) to determine the effect of animal food ingestion on methylamine concentrations.


Asunto(s)
Betaína/análisis , Carnitina/análisis , Colina/análisis , Creatinina/análisis , Metilaminas/análisis , Betaína/sangre , Betaína/orina , Carnitina/análogos & derivados , Carnitina/sangre , Carnitina/orina , Colina/sangre , Colina/orina , Cromatografía Liquida/métodos , Creatinina/sangre , Creatinina/orina , Femenino , Análisis de los Alimentos/métodos , Humanos , Límite de Detección , Masculino , Metilaminas/sangre , Metilaminas/orina , Persona de Mediana Edad , Espectrometría de Masas en Tándem/métodos
5.
Surg Endosc ; 35(12): 7183-7190, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33258032

RESUMEN

BACKGROUND: Perforated peptic ulcer is a life-threatening condition. Traditional treatment is surgery. Esophageal perforations and anastomotic leakages can be treated with endoscopically placed covered stents and drainage. We have treated selected patients with a perforated duodenal ulcer with a partially covered stent. The aim of this study was to compare surgery with stent treatment for perforated duodenal ulcers in a multicenter randomized controlled trial. METHODS: All patients presenting at the ER with abdominal pain, clinical signs of an upper G-I perforation, and free air on CT were approached for inclusion and randomized between surgical closure and stent treatment. Age, ASA score, operation time, complications, and hospital stay were recorded. Laparoscopy was performed in all patients to establish diagnosis. Surgical closure was performed using open or laparoscopic techniques. For stent treatment, a per-operative gastroscopy was performed and a partially covered stent was placed through the scope. Abdominal lavage was performed in all patients, and a drain was placed. All patients received antibiotics and intravenous PPI. Stents were endoscopically removed after 2-3 weeks. Complications were recorded and classified according to Clavien-Dindo (C-D). RESULTS: 43 patients were included, 28 had a verified perforated duodenal ulcer, 15 were randomized to surgery, and 13 to stent. Median age was 77.5 years (23-91) with no difference between groups. ASA score was unevenly distributed between the groups (p = 0.069). Operation time was significantly shorter in the stent group, 68 min (48-107) versus 92 min (68-154) (p = 0.001). Stents were removed after a median of 21 days (11-37 days) without complications. Six patients in the surgical group had a complication and seven patients in the stent group (C-D 2-5) (n.s.). CONCLUSIONS: Stent treatment together with laparoscopic lavage and drainage offers a safe alternative to traditional surgical closure in perforated duodenal ulcer. A larger sample size would be necessary to show non-inferiority regarding stent treatment.


Asunto(s)
Úlcera Duodenal , Laparoscopía , Úlcera Péptica Perforada , Anciano , Úlcera Duodenal/complicaciones , Úlcera Duodenal/cirugía , Humanos , Úlcera Péptica Perforada/cirugía , Estudios Prospectivos , Stents , Resultado del Tratamiento
6.
JGH Open ; 4(3): 405-409, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32514445

RESUMEN

BACKGROUND AND AIM: Microbial contamination of the abdominal cavity is a serious concern during transgastric endoscopic interventions and perforations, particularly in patients who have inhibited gastric acid secretion due to treatment with proton pump inhibitors (PPIs).The aim of this study was to investigate the gastric and duodenal bacterial flora in patients with and without PPI treatment. METHODS: Patients referred for gastroscopy, without recent antibiotic treatment, were eligible for inclusion. Use of PPIs was recorded. Samples for bacterial culturing were obtained from the antrum of the stomach and from the duodenal bulb through a gastroscope. Positive cultures were examined for bacterial types and subtypes. Biopsies were taken in the antrum for urease test to detect Helicobacter pylori. RESULTS: Bacterial cultures from the stomach were obtained from 103 patients, and duodenal samples were also cultured from 49 of them, for a total of 53 patients with PPI use and 50 patients without. Positive gastric cultures were found in 42 of 53 patients with PPI use and in 13 of 50 without (P < 0.0001). Duodenal cultures were positive in 20 of 24 with PPI and 8 of 25 without (P < 0.0001). The most commonly identified bacterial species were oral strains of Streptococcus, followed by Neisseria and Haemophilus influenzae. Of 103 patients, 10 had a positive urease test, indicating H. pylori infection, 1 with PPI and 9 without. CONCLUSIONS: Bacterial growth in the stomach and duodenum is more common in patients with PPI treatment. The dominating bacterial species found in the stomach and duodenum originates from the oropharynx. Clinical trials registry: Trial registration number 98041 in Researchweb (FoU in Sweden).

7.
Chemistry ; 26(44): 10024-10034, 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32449563

RESUMEN

Ligand-based NMR techniques to study protein-ligand interactions are potent tools in drug design. Saturation transfer difference (STD) NMR spectroscopy stands out as one of the most versatile techniques, allowing screening of fragments libraries and providing structural information on binding modes. Recently, it has been shown that a multi-frequency STD NMR approach, differential epitope mapping (DEEP)-STD NMR, can provide additional information on the orientation of small ligands within the binding pocket. Here, the approach is extended to a so-called DEEP-STD NMR fingerprinting technique to explore the binding subsites of cholera toxin subunit B (CTB). To that aim, the synthesis of a set of new ligands is presented, which have been subject to a thorough study of their interactions with CTB by weak affinity chromatography (WAC) and NMR spectroscopy. Remarkably, the combination of DEEP-STD NMR fingerprinting and Hamiltonian replica exchange molecular dynamics has proved to be an excellent approach to explore the geometry, flexibility, and ligand occupancy of multi-subsite binding pockets. In the particular case of CTB, it allowed the existence of a hitherto unknown binding subsite adjacent to the GM1 binding pocket to be revealed, paving the way to the design of novel leads for inhibition of this relevant toxin.


Asunto(s)
Toxina del Cólera/química , Toxina del Cólera/metabolismo , Gangliósido G(M1)/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Simulación de Dinámica Molecular , Sitios de Unión , Ligandos , Unión Proteica
8.
PLoS One ; 15(1): e0228200, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31990946

RESUMEN

Earlier studies have implied a change in dietary habits of the Swedish population towards a low carbohydrate, high fat diet. Questions have been raised about the development in recent years and potential health effects. We have investigated the dietary intake of Swedish female students enrolled in a university nutrition course between 2002 and 2017. The students carried out self-reporting of all food and drink intake over one weekday and one weekend day. Intake of macronutrients (E%) and micronutrients were calculated for the whole period while statistical analysis was performed for changes between 2009 and 2017 (729 women). Results showed significant changes in carbohydrate intake (from 47.0 to 41.4 E%) and fat intake (from 31.7 to 37.5 E%). Carbohydrate intake was significantly lower than the Nordic Nutrition Recommendations (45-60 E%). However, daily fiber intake remains high (3.0 g/MJ) in a national context, and intake of vitamin D and folate appears to increase during the period. The results suggest that the observed national transition from carbohydrate to fat intake persists, and that it might be especially evident among individuals interested in food and nutrition. Considering the fiber and micronutrient intake, the change is not necessarily unfavorable for this particular group.


Asunto(s)
Carbohidratos de la Dieta/análisis , Grasas de la Dieta/análisis , Ingestión de Alimentos , Ciencias de la Nutrición , Estudiantes/estadística & datos numéricos , Proteínas en la Dieta/análisis , Metabolismo Energético , Conducta Alimentaria , Femenino , Humanos , Masculino , Suecia , Adulto Joven
9.
Disabil Rehabil ; 42(3): 385-393, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30634863

RESUMEN

Purpose: To describe the meaning of significant others in relation to participation in everyday life of persons with early diagnosed rheumatoid arthritis (RA).Materials and methods: Fifty-nine persons participated in this interview study. Inclusion criteria were three years' experience of diagnosis and being of working age. Semi-structured interviews were conducted using critical incident technique (CIT), and the material was analysed using content analysis.Results: Four categories were revealed: (1) My early RA causes activity adaptations for us all, referring to the person and significant others modifying activities. (2) Making the significant others balance between shortfalls and participation, where the participants distinguished between needing help and feeling involved in activities. (3) Physical interactions with significant others, referring to both the problematic and manageable impact RA could have on body contact. (4) Emotions in relation to activities with others, where participants described feelings of failing others, and anxiety about future activities.Conclusions: For persons with early diagnosed RA, significant others can be both hindering and facilitating for participation in everyday life. As a clinical implication, it is valuable to identify how significant others can be involved in the rehabilitation process, to enhance participation in everyday life early in the disease process.Implications for rehabilitationSignificant others of persons with rheumatoid arthritis can facilitate as well as hinder participation in everyday life, even early in the disease process.It is important to include the significant others in the rehabilitation process of persons with early diagnosed rheumatoid arthritis.It is of great importance to identify when and how significant others can be facilitators of participation in everyday life for persons with early rheumatoid arthritis.To make it easier for significant others to facilitate participation, there is a need for the healthcare system to explore ways to support significant others with easily accessible information about early rheumatoid arthritis.


Asunto(s)
Actividades Cotidianas/psicología , Artritis Reumatoide , Personas con Discapacidad , Participación del Paciente/psicología , Calidad de Vida , Edad de Inicio , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/psicología , Artritis Reumatoide/rehabilitación , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Medio Social , Suecia
10.
Scand J Gastroenterol ; 54(10): 1269-1273, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31553628

RESUMEN

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016-2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.


Asunto(s)
Cólico/virología , Cálculos Biliares/virología , Genotipo , Virus de la Hepatitis E/genética , Hepatitis E/diagnóstico , Pancreatitis/virología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cólico/diagnóstico , Femenino , Estudios de Seguimiento , Cálculos Biliares/diagnóstico , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Hepatitis E/virología , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Prevalencia , Estudios Prospectivos , ARN Viral/análisis , Suecia , Adulto Joven
11.
Neurogastroenterol Motil ; 30(12): e13445, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30109904

RESUMEN

BACKGROUND: Perforated duodenal ulcers can be treated with a covered stent. Stent migration is a severe complication, sometimes requiring surgery. Pyloric physiology during stent treatment has not been studied and mechanisms for migration are unknown. The aim of this study was to investigate the pyloric response to distention, mimicking stent treatment, using the EndoFLIP. METHODS: A nonsurvival study in five pigs was carried out, followed by a pilot study in one volunteer. Animals were gastroscoped during anaesthesia and the EndoFLIP was placed straddling the pylorus. Baseline distensibility readings were performed at stepwise balloon distentions to 20, 30, 40, and 50 mL, measuring pyloric cross-sectional area and pressure. Measurements were repeated after administration of a prokinetic drug and after a liquid meal. In the human study, readings were performed in conscious sedation at baseline and after stimulation with metoclopramide. KEY RESULTS: During baseline readings, the pylorus was shown to open more with increasing distention together with higher amplitude motility waves. Reaching maximum distention-volume (50 mL), pyloric pressure increased significantly (P = 0.016), and motility waves disappeared. After prokinetic stimulation, the pressure decreased and the motility waves increased in frequency and amplitude. After food stimulation, the pressure stayed low and the motility showed increase in amplitude. During both tests, the pylorus showed higher pressure and lack of motility waves at maximum probe distention. CONCLUSIONS AND INFERENCES: The pylorus seems to act as a sphincter at low distention but when further dilated starts acting as a pump. Fully distended the pyloric motility disappears and the pressure remains high, suggesting that a stent with high-radial force might show less migration.


Asunto(s)
Migración de Cuerpo Extraño/fisiopatología , Píloro/fisiología , Stents/efectos adversos , Animales , Úlcera Duodenal/cirugía , Motilidad Gastrointestinal/fisiología , Humanos , Proyectos Piloto , Porcinos
12.
Ann Transl Med ; 5(9): 199, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28567379

RESUMEN

Video capsule endoscopy (VCE) has become the method of choice for visualizing the small bowel mucosa and is generally considered to be a safe method. Although uncommon, the most feared complication of VCE is capsule retention that can potentially lead to life-threatening bowel obstruction. Herein, we present for the first time a case of capsule retention in a colonic stent. The patient had known Crohn's disease with colonic involvement and underwent an uneventful but incomplete small bowel VCE for assessment of disease activity and extension for optimizing medical treatment. Five months later, the patient presented with intestinal obstruction due to a Crohn's-stricture in the sigmoid colon, which was successfully decompressed with a self-expandable metal stent. Nonetheless, two days later the patient showed signs of bowel obstruction again and abdominal X-ray showed that the capsule was trapped in the metal stent in the sigmoid colon. Subsequently, emergency surgery was performed and the patient fully recovered. Intestinal capsule retention necessitating interventional removal is rare. This report describes a unique case of capsule retention in a colonic metal stent and highlights the potential risk of performing capsule endoscopy examinations in patients with gastrointestinal stents.

13.
Scand J Occup Ther ; 24(6): 468-476, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28052711

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with disability. Despite new treatments, pain and activity limitations are still present. OBJECTIVES: To describe how persons with RA experience and manage pain in their daily life. METHODS: Seven semi-structured focus groups (FGs) were conducted and analyzed using content analysis. RESULTS: The analysis revealed four categories: 1) Pain expresses itself in different ways referred to pain as overwhelming, aching or as a feeling of stiffness. 2) Mitigating pain referred to the use of heat, cold, medications and activities as distractions from the pain. 3) Adapting to pain referred to strategies employed as coping mechanisms for the pain, e.g. planning and adjustment of daily activities, and use of assistive devices. 4) Pain in a social context referred to the participants' social environment as being both supportive and uncomprehending, the latter causing patients to hide their pain. CONCLUSIONS: Pain in RA is experienced in different ways. This emphasizes the multi-professional team to address this spectrum of experiences and to find pain management directed to the individual experience that also include the person's social environment.


Asunto(s)
Adaptación Psicológica , Artritis Reumatoide/rehabilitación , Manejo del Dolor/métodos , Dolor/psicología , Actividades Cotidianas , Personas con Discapacidad/psicología , Grupos Focales , Humanos , Terapia Ocupacional , Manejo del Dolor/psicología , Investigación Cualitativa , Dispositivos de Autoayuda
14.
J Laparoendosc Adv Surg Tech A ; 26(7): 511-6, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27163486

RESUMEN

BACKGROUND: Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α). METHODS: Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed. RESULTS: CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections. CONCLUSIONS: This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.


Asunto(s)
Cirugía Endoscópica por Orificios Naturales , Gastropatías/cirugía , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Femenino , Laparoscopía , Complicaciones Posoperatorias , Distribución Aleatoria , Gastropatías/sangre , Porcinos , Factor de Necrosis Tumoral alfa/sangre
15.
Analyst ; 141(3): 981-8, 2016 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-26673836

RESUMEN

Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures.


Asunto(s)
Cromatografía de Afinidad/métodos , Evaluación Preclínica de Medicamentos/métodos , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Acuaporina 1/química , Acuaporina 1/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Porosidad , Dióxido de Silicio/química
16.
Lakartidningen ; 1122015 Sep 29.
Artículo en Sueco | MEDLINE | ID: mdl-26418934

RESUMEN

Despite modern treatment of ulcer disease perforations still occur and constitute a life threatening complication. Standard treatment is surgical closure. We have introduced stent treatment as a minimal invasive alternative, mainly in elderly and co-morbid patients. During a 4-year period (2009-2012) ten patients with perforated duodenal ulcer were treated with a covered duodenal stent at South Älvsborg Hospital. These patients were retrospectively compared with all patients (n = 19) treated with surgical closure at the same hospital during the same time period. Stent treatment shows good clinical results indicating fewer complications than surgical treatment even if the patients had a slightly higher ASA score. In this series stent treatment is shown to be a safe and effective alternative for treating perforated duodenal ulcers, even in old and co-morbid patients.


Asunto(s)
Úlcera Duodenal/complicaciones , Úlcera Péptica Perforada/cirugía , Stents , Anciano , Anciano de 80 o más Años , Comorbilidad , Drenaje , Femenino , Gastroscopía , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
17.
Anal Biochem ; 461: 57-9, 2014 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-24915639

RESUMEN

In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-µM) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (KD) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R(2)=0.995, P<0.0001).


Asunto(s)
Cromatografía de Afinidad/métodos , Bibliotecas de Moléculas Pequeñas/metabolismo , Resonancia por Plasmón de Superficie/métodos , Trombina/metabolismo , Humanos , Cinética , Unión Proteica
18.
PLoS One ; 9(3): e92321, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24647540

RESUMEN

The complete nucleotide sequence of plasmids pMCBF1 and pMCBF6 was determined and analyzed. pMCBF1 and pMCBF6 form a novel clade within the IncP-1 plasmid family designated IncP-1 ς. The plasmids were exogenously isolated earlier from a marine biofilm. pMCBF1 (62 689 base pairs; bp) and pMCBF6 (66 729 bp) have identical backbones, but differ in their mercury resistance transposons. pMCBF1 carries Tn5053 and pMCBF6 carries Tn5058. Both are flanked by 5 bp direct repeats, typical of replicative transposition. Both insertions are in the vicinity of a resolvase gene in the backbone, supporting the idea that both transposons are "res-site hunters" that preferably insert close to and use external resolvase functions. The similarity of the backbones indicates recent insertion of the two transposons and the ongoing dynamics of plasmid evolution in marine biofilms. Both plasmids also carry the insertion sequence ISPst1, albeit without flanking repeats. ISPs1is located in an unusual site within the control region of the plasmid. In contrast to most known IncP-1 plasmids the pMCBF1/pMCBF6 backbone has no insert between the replication initiation gene (trfA) and the vegetative replication origin (oriV). One pMCBF1/pMCBF6 block of about 2.5 kilo bases (kb) has no similarity with known sequences in the databases. Furthermore, insertion of three genes with similarity to the multidrug efflux pump operon mexEF and a gene from the NodT family of the tripartite multi-drug resistance-nodulation-division (RND) system in Pseudomonas aeruginosa was found. They do not seem to confer antibiotic resistance to the hosts of pMCBF1/pMCBF6, but the presence of RND on promiscuous plasmids may have serious implications for the spread of antibiotic multi-resistance.


Asunto(s)
Secuencia de Bases/genética , Biopelículas/crecimiento & desarrollo , Plásmidos/genética , Agua de Mar/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Filogenia , Resolvasas de Transposones/genética
19.
Surg Endosc ; 28(8): 2421-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24619329

RESUMEN

BACKGROUND: NOTES is believed to induce less surgical trauma than open and laparoscopic surgery. The degree of surgical trauma can be assessed by measuring serum levels of acute-phase proteins such as CRP and TNF-α. We conducted a prospective randomized survival trial in which the inflammatory responses after laparoscopic, open, and NOTES transgastric uterine horn resection were compared. The aim of this study was to investigate whether NOTES procedures induce less inflammatory response. METHODS: Thirty pigs were randomized into three groups to undergo open, laparoscopic, or transgastric uterine horn resection. Weight, body temperature, and postoperative recovery were recorded and venous blood samples were taken for analysis of CRP and TNF-α at different time points. Analyses of CRP and TNF-α were performed using pig-specific ELISA assays. RESULTS: Procedure time was significantly longer for NOTES [median = 121 min (range = 94-155)] compared with that for open surgery [median = 22 min (14-27)] and laparoscopy [median = 37 min (20-45)] (p < 0.0001). There was a nonsignificant tendency for shorter recovery time for the NOTES animals. Twenty-seven animals survived for 4 weeks. One animal in each group was euthanized prior to 4 weeks. All animals gained weight during the 4-week period with no significant differences. Only animals in the NOTES group showed a significant weight gain during the first postoperative week (p = 0.007). On postoperative day (POD) 1, CRP was significantly lower in the NOTES group compared with the open and laparoscopic groups (mean = 0.72 ± 0.22, 0.98 ± 0.26, and 0.97 ± 0.20, respectively; p = 0.048). The CRP levels were normalized on day 14. Throughout the study there were no significant changes in TNF-α levels in the laparoscopic and NOTES groups. At POD 3 the open surgery group showed significantly higher TNF-α levels than the other groups (p = 0.036). CONCLUSIONS: Despite the longer operating time, the transgastric NOTES approach seems to be less traumatic than open or laparoscopic uterine horn resection in this porcine model.


Asunto(s)
Proteína C-Reactiva/análisis , Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Factor de Necrosis Tumoral alfa/sangre , Útero/cirugía , Periodo de Recuperación de la Anestesia , Animales , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Tempo Operativo , Estudios Prospectivos , Distribución Aleatoria , Porcinos , Aumento de Peso
20.
Int J Surg ; 11(9): 977-82, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23796443

RESUMEN

BACKGROUND: Peritoneal adhesions are a clinical problem. A key to the understanding of peritoneal adhesions is to study the healing of mesothelial cells within the peritoneal cavity following surgery. Transforming growth factor beta (TGF-ßs) affects this healing process. The aim of this study was to investigate the effects of different concentrations of TGF-ß1 on the healing rate and healing properties of mesothelial cells. MATERIALS AND METHODS: Human mesothelial cells from peritoneal fluid were collected, cultured and a mechanical wound was created. The restoration of the mesothelial surface with and without increasing concentrations of TGF-ß1 was monitored. RESULTS: The denuded area was restored within 24 h. The healing rate was most extensive between the first and second hour after the damage (61.9 ± 22.8 µm/h). No significant difference in healing rate were observed when increasing levels of TGF-ß1 were used. However, higher concentrations of TGF-ß1 increased cell size and the cells presented more fibroblast specific properties. Lower TGF-ß1 concentrations increased the number of proliferating cells. CONCLUSIONS: This study indicates the importance of high levels TGF-ß1 in mesothelial cell healing, mainly by changing the actual healing properties of the cells. Elevated levels of TGF-ß1 might promote mesothelial cell transition towards a more fibroblast-like appearance.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Mesodermo/citología , Peritoneo/citología , Factor de Crecimiento Transformador beta1/farmacología , Cicatrización de Heridas/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Mesodermo/efectos de los fármacos , Modelos Biológicos , Peritoneo/efectos de los fármacos , Peritoneo/lesiones , Fenotipo , Adherencias Tisulares/metabolismo , Adherencias Tisulares/prevención & control
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