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BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children. OBJECTIVES: This study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception. MATERIALS AND METHODS: All live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups. RESULTS: There was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram. DISCUSSION AND CONCLUSION: Although the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.

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BACKGROUND: Elderly patients with inflammatory bowel disease [IBD] are fragile in many respects. Therefore, in these patients, we studied postoperative complications [new abdominal surgery and serious infections after the first IBD surgery]. METHODS: This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis [UC] and Crohn's disease [CD]. The exposed cohort [elderly] constituted those at an age of ≥60 years at first IBD surgery, and the unexposed [adults] those with surgery at the age of 18-59 years. We estimated adjusted hazard ratios [aHRs] of: a] new abdominal surgery within 2 years; and b] serious [hospital-diagnosed] infections within 6 and 12 months. We adjusted for several confounders including type of index surgery [laparoscopic or open]. RESULTS: The aHR for a new surgery among elderly with UC and CD were 0.69 [95% CI 0.58-0.83] and 0.98 [95% CI 0.83-1.15], respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 [95% CI 0.81-1.40] and 0.85 [95% CI 0.67-1.08], respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 [95% CI 1.12-1.88] and 1.26 [95% CI 1.00-1.59], respectively. CONCLUSION: The elderly with IBD did not have an increased risk of new abdominal surgery within 2 years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery.

Asunto(s)

Colitis Ulcerosa , Enfermedad de Crohn , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Dinamarca/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/complicaciones , Estudios de Cohortes , Adolescente , Sistema de Registros , Adulto Joven , Enfermedades Inflamatorias del Intestino/cirugía , Enfermedades Inflamatorias del Intestino/complicaciones , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Factores de Riesgo , Modelos de Riesgos Proporcionales , Factores de Edad

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INTRODUCTION: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. METHODS: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. RESULTS: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. CONCLUSION: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients' 5-year adherence to VIT was higher than patients' 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI.

Asunto(s)

Anafilaxia , Mordeduras y Picaduras de Insectos , Mastocitosis , Hipersensibilidad al Veneno , Masculino , Femenino , Humanos , Epinefrina/uso terapéutico , Estudios Retrospectivos , Medicina Estatal , Anafilaxia/epidemiología , Anafilaxia/etiología , Desensibilización Inmunológica/efectos adversos , Alérgenos , Inmunoterapia

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We developed four algorithms for the automatic capture of C-reactive protein (CRP) peaks in 296 adult patients with acute myeloid leukemia who had bloodstream infection (BSI) episodes, negative blood cultures (BCs) or possible infections where no BCs were performed. The algorithms detected CRP peaks for 418-446 of the 586 documented BSI episodes (71.3-76.1%) and 2714-3118 of the 4382 negative BCs (61.9-71.2%). The four algorithms captured 382-789 CRP peaks in which there were neither BSI episodes nor negative BCs. We conclude that automatic capture of CRP peaks is a tool for the monitoring of BSI episodes and possibly other infections in patients with acute myeloid leukemia.

Asunto(s)

Bacteriemia , Leucemia Mieloide Aguda , Sepsis , Adulto , Humanos , Proteína C-Reactiva/metabolismo , Biomarcadores , Sepsis/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Estudios Retrospectivos

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BACKGROUND AND AIM: Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). METHODS: We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. RESULTS: We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. CONCLUSIONS: Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

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BACKGROUND: It is mandatory to label food products with the 14 main allergens in the EU. Reasonable allergen labeling requires knowledge of population-based thresholds derived from food challenges. The aim of this study was to evaluate the threshold-distribution in clinically verified food allergic patients for allergens mandatory for labeling. METHODS: All positive open oral food challenges and double-blind placebo-controlled food challenges (DBPCFC) performed at the Allergy Center, Odense University Hospital, Denmark (2000-2022) were included. For each included challenge, the cumulative threshold (LOAEL) was obtained and NOAEL estimated. Data were modelled as an interval censored log-normal distribution. RESULTS: Overall, 38 of all 2612 challenges (1.5%) in 1229 patients (717 male, 986 children) reacted to <5 mg protein. The majority of the most sensitive patients reacted with a Sampson severity score of 2-3. Using interval censored log-normal models only five groups (hens´ egg, fish, peanut, milk, tree-nuts) elicited reactions after ingestion of 0.5 mg protein and in low frequencies of the population. Hen's egg was the most potent allergen, with reactivity to <0.5 mg protein in 0.24% [0.13-0.44%] of egg allergic patients while the estimated fraction of allergic patients reacting to a eliciting dose on 0.5 mg protein for most other allergens were below 0.04%. CONCLUSION: Our data demonstrates that the majority of food allergic patients as expected tolerating traces of allergenic foods without developing severe allergic symptoms and signs. Hen's egg appears to be the food most likely to elicit reactions in the most sensitive individuals at very low doses.

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Aims: The aim of this study was to evaluate whether patients with a non-specific back pain disorder are more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder (such as a herniated disc or inflammatory back disorder). Methods: This was a retrospective cohort study using Danish registries. Results: Our study population included 24,518 patients younger than 61 years and 12,274 patients older than 61 years. In both subpopulations, 60% had a non-specific back pain diagnosis (BPD). In the younger subpopulation, 2.1% of the patients with a non-specific BPD and 1.3% of the patients with a specific BPD had a psychiatric diagnosis within one year of their BPD. In the older subpopulation, 0.6% of patients had a psychiatric diagnosis in both BPD groups. The most frequent psychiatric diagnoses were stress-related disorders. In the younger subpopulation, patients with non-specific back pain had a higher risk of being diagnosed with a psychiatric disorder than patients with specific back pain (adjusted odds ratio 1.56, 95% confidence interval 1.25-1.94). The type of BPD had no effect on the risk of having a psychiatric diagnosis among older patients. Conclusions: Patients with a non-specific back pain disorder younger than 61 years were more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder. We recommend that spine specialists pay special attention to patients younger than 61 years with a back pain disorder to prevent them from developing a psychiatric disorder.

Asunto(s)

Trastornos Mentales , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Dolor de Espalda/diagnóstico , Dolor de Espalda/epidemiología , Trastornos Somatomorfos

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BACKGROUND: Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce. AIM: To examine the risk of childhood infections associated with fathers' use of anti-inflammatory/immunosuppressive medications taken before conception. METHODS: This is a nationwide cohort study based on Danish health registries, comprising all live-born singleton children born between January 1997 and February 2019 who were fathered by men with IBD. Exposed cohorts included children fathered by men treated with 5-aminosalicylates (5-ASAs), thiopurines, corticosteroids or anti-tumour necrosis factor-α (anti-TNF-α) agents within 3 months before conception. The unexposed cohort included children not exposed to paternal IBD medications. Outcomes were the first infection, diagnosed in the hospital setting in the first year of life, and from the age of 1 to 3 years. RESULTS: In all, 2178 children were fathered by men exposed to 5-ASAs, 843 to thiopurines, 417 to systemic corticosteroids and 436 to anti-TNF-α agents; 6799 children were unexposed. The adjusted hazard ratio (aHR) for infections within the first year of life for 5-ASAs was 0.78 (95% CI, 0.66-0.91), thiopurines 0.89 (95% CI, 0.73-1.09), systemic corticosteroids 0.95 (95% CI, 0.70-1.29), and anti-TNF-α agents 1.17 (95% CI, 0.94-1.46). The aHR for infections from 1 to 3 years for 5-ASAs was 0.97 (95% CI, 0.83-1.13), thiopurines 0.87 (95% CI, 0.71-1.07), systemic corticosteroids 1.25 (95% CI, 0.94-1.65), and anti-TNF-α agents 0.79 (95% CI, 0.60-1.03). CONCLUSION: Fathers' use of anti-inflammatory/immunosuppressive medications before conception was not significantly associated with childhood infections. These results fill an important research gap regarding paternal medication safety.

Asunto(s)

Enfermedades Inflamatorias del Intestino , Inhibidores del Factor de Necrosis Tumoral , Corticoesteroides/uso terapéutico , Antiinflamatorios/uso terapéutico , Preescolar , Estudios de Cohortes , Padre , Hospitales , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/efectos adversos , Lactante , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Factor de Necrosis Tumoral alfa/uso terapéutico

RESUMEN

BACKGROUND: Patients with back pain are often in contact with 2-4 hospital departments when receiving a back pain diagnosis and treatment. This complicates the entire clinical course description. There is, currently, no model that describes the course across departments for patients with back pain. This study aims to construct an interdisciplinary clinical course using the central register's information. METHODS: All patients with back pain referred for diagnosis and treatment at the Spine Center of Southern Denmark from 1 January 2011 until 31 December 2017 were included. By means of information available in central registers, we described the interdisciplinary clinical course for the individual patient, including information on all contacts at different departments, and proposed three different models to define the index and final date. The index date was defined as the first visit without a previous contact to the Spine Center for 6 months for model I, 1 year for model II, and 2 years for model III. The final date was defined as the last visit without following contacts for 6 months, 1 year, and 2 years, respectively, for models I, II, and III. RESULTS: A total of 69,564 patients (male: n = 30,976) with back pain diagnosis were identified. The three models all leave the information on the entire course at the hospital. In model I (64,757 clinical back pain courses), the time span to a possible previous clinical course is too short to secure the start of a new course (14% had two or more). With at least 1 year between a possible previous contact, model II (60,914 courses) fits the everyday clinical practice (9% had two or more clinical back pain courses). In model III (60,173 courses) it seems that two independent courses might be connected in the same course as only 5% had two or more clinical back pain courses. CONCLUSIONS: Despite contact with different departments, the clinical course for back pain patients can be described by information from the central registers. A one-year time interval fits best the clinicians' everyday observations.

Asunto(s)

Dolor de la Región Lumbar , Dolor de Espalda/diagnóstico , Dolor de Espalda/epidemiología , Dolor de Espalda/terapia , Dinamarca/epidemiología , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/epidemiología , Dolor de la Región Lumbar/terapia , Masculino , Derivación y Consulta , Sistema de Registros

RESUMEN

OBJECTIVES: Many factors contribute to the plasma albumin (PA) level. We aimed to quantify different factors' relative contribution to the PA level when diagnosing hematological malignancy (HM). METHODS: The study was a population-based registry study including patients with HM in a Danish region. We applied multivariate linear regression analyses with C-reactive protein (CRP), WHO performance score (WHO-PS), age, sex, comorbidity, and HM type as exposures and the PA level on the day of the HM diagnosis (DX) as the outcome. The relative contribution of each exposure was determined as a percentage of the models' coefficient of determination (R2). RESULTS: In total, 2528 patients with HM had PA measured on DX. In the model comprising all exposures, CRP contributed with 65.8% to the R2 of 0.389 whereas 3 variables (CRP, WHO-PS, HM type) together contributed with 96.1%. When CRP was excluded from the model, R2 declined to 0.215 and the WHO-PS contributed with 96%. Other models, including separate analyses for each HM type, corroborated these results, except in myeloma patients where WHO-PS contributed with 61.1% to the R2 of 0.234. CONCLUSION: The inflammation biomarker CRP was the main predictor of the PA level on DX. The WHO-PS also contributed to the PA level on DX whereas the remaining factors (HM type, age, sex, and comorbidity) were of much less importance.

Asunto(s)

Neoplasias Hematológicas/sangre , Albúmina Sérica/análisis , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Comorbilidad , Dinamarca/epidemiología , Femenino , Neoplasias Hematológicas/clasificación , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores Sexuales , Adulto Joven

RESUMEN

OBJECTIVES: We assessed C-reactive protein (CRP) and plasma albumin (PA) kinetics to evaluate community-acquired bloodstream infection (CA-BSI) patients' 1-year outcomes. METHODS: Population-based study, with CRP and PA measurements on day 1 (D1) and D4. Relative CRP variations in relation to D1 CRP value were evaluated (CRP-ratio). Patients were classified as fast response, slow response, non-response, and biphasic response. RESULTS: A total of 935 patients were included. At D4, the CRP-ratio was lower in survivors on D365 in comparison with D4-D30 non-survivors and D30-D365 non-survivors (p<0.001). In comparison with fast response patients, non-response and biphasic response patients had 2.74 and 5.29 increased risk, respectively, of death in D4-D30 and 2.77 and 3.16 increased risk, respectively, of death in D31-D365. PA levels remained roughly unchanged from D1-D4, but lower D1 PA predicted higher short and long-term mortality (p<0.001). The discriminative performance of the CRP-ratio and D1 PA to identify patients with poor short and long-term mortality after adjustments was acceptable (AUROC=0.79). CONCLUSIONS: Serial CRP measurements at D1 and D4 after CA-BSI is clinically useful to identify patients with poor outcome. Individual patterns of CRP-ratio response with PA at D1 further refine our ability of predicting short or long-term mortality.

Asunto(s)

Bacteriemia/mortalidad , Proteína C-Reactiva/análisis , Infecciones Comunitarias Adquiridas/mortalidad , Albúmina Sérica/análisis , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/sangre , Bacteriemia/tratamiento farmacológico , Biomarcadores/sangre , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

BACKGROUND: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML). METHODS: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days). RESULTS: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event. CONCLUSIONS: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Asunto(s)

Bacteriemia/metabolismo , Proteína C-Reactiva/análisis , Leucemia Mieloide Aguda/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Albúmina Sérica/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/mortalidad , Biomarcadores de Tumor/análisis , Dinamarca , Regulación hacia Abajo , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven

RESUMEN

Higher sterols are universally present in large amounts (20-30%) in the plasma membranes of all eukaryotes whereas they are universally absent in prokaryotes. It is remarkable that each kingdom of the eukaryotes has chosen, during the course of evolution, its preferred sterol: cholesterol in animals, ergosterol in fungi and yeast, phytosterols in higher plants, and e.g., fucosterol and desmosterol in algae. The question arises as to which specific properties do sterols impart to membranes and to which extent do these properties differ among the different sterols. Using a range of biophysical techniques, including calorimetry, fluorescence microscopy, vesicle-fluctuation analysis, and atomic force microscopy, we have found that fucosterol and desmosterol, found in red and brown macroalgae (seaweeds), similar to cholesterol support liquid-ordered membrane phases and induce coexistence between liquid-ordered and liquid-disordered domains in lipid bilayers. Fucosterol and desmosterol induce acyl-chain order in liquid membranes, but less effectively than cholesterol and ergosterol in the order: cholesterol>ergosterol>desmosterol>fucosterol, possibly reflecting the different molecular structure of the sterols at the hydrocarbon tail.

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Desmosterol/química , Membrana Dobles de Lípidos/química , Algas Marinas/química , Estigmasterol/análogos & derivados , Rastreo Diferencial de Calorimetría , Membrana Celular , Fenómenos Mecánicos , Microscopía de Fuerza Atómica , Microscopía Fluorescente , Estructura Molecular , Estigmasterol/química

RESUMEN

Cholesterol with BODIPY at carbon-24 of the side chain (BCh2) has recently been introduced as new cholesterol probe with superior fluorescence properties. We compare BCh2 with the intrinsically fluorescent dehydroergosterol (DHE), a well-established marker for cholesterol, by introducing simultaneous imaging of both sterols in model membranes and living cells. BCh2 had a lower affinity than DHE for the biologically relevant liquid-ordered phase in model membranes. Still, DHE and BCh2 trafficked from the plasma membrane to the endocytic recycling compartment (ERC) of BHK cells with identical kinetics. This transport pathway was strongly reduced after energy depletion of cells or expression of the dominant-negative clathrin heavy chain. The partitioning into lipid droplets of BHK and HeLa cells was higher for BCh2 than for DHE. Within droplets, the photodegradation of BCh2 was enhanced and followed a stretched exponential decay, while the fluorescence lifetime of BCh2 was comparable in various cellular regions. Our results indicate that BCh2 is suitable for analyzing sterol uptake pathways and inter-organelle sterol flux in living cells. The BODIPY-moiety affects lipid phase preference of the sterol probe and causes some differential targeting of BCh2 and DHE in cells with high fat content.

Asunto(s)

Compuestos de Boro/química , Colesterol/química , Ergosterol/análogos & derivados , Colorantes Fluorescentes/química , Compuestos de Boro/metabolismo , Células Cultivadas , Colesterol/metabolismo , Ergosterol/química , Ergosterol/metabolismo , Colorantes Fluorescentes/metabolismo , Células HeLa , Humanos , Estructura Molecular , Coloración y Etiquetado , Estereoisomerismo

RESUMEN

The fluorescent sterol dehydroergosterol (DHE) is often used as a marker for cholesterol in cellular studies. We show by vesicle fluctuation analysis that DHE has a lower ability than cholesterol to stiffen lipid bilayers suggesting less efficient packing with phospholipid acyl chains. Despite this difference, we found by fluorescence and atomic force microscopy, that DHE induces liquid-ordered/-disordered coexistent domains in giant unilamellar vesicles (GUVs) and supported bilayers made of dipalmitoylphosphatidylcholine (DPPC), dioleylphosphatidylcholine (DOPC) and DHE or cholesterol. DHE-induced phases have a height difference of 0.9-1 nm similar as known for cholesterol-containing domains. DHE not only promotes formation of liquid-liquid immiscibility but also shows strong partition preference for the liquid-ordered phase further supporting its suitability as cholesterol probe.

Asunto(s)

Ergosterol/análogos & derivados , Colorantes Fluorescentes/química , Membranas Artificiales , 1,2-Dipalmitoilfosfatidilcolina/química , Colesterol/química , Ergosterol/química , Membrana Dobles de Lípidos/química , Microscopía Fluorescente , Fosfatidilcolinas/química , Liposomas Unilamelares/química