RESUMEN
OBJECTIVE: To investigate the associations between complement C3d and inflammatory and structural changes by magnetic resonance imaging (MRI) at the sacroiliac joints (SIJ) suggestive of axial spondyloarthritis, according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, in patients with low back pain. METHOD: This was a cross-sectional study of patients referred to the Spine Centre of Southern Denmark owing to unspecified low back pain (Spines of Southern Denmark cohort). The patients were divided into three groups: group 1: patients fulfilling the ASAS criteria for axial spondyloarthritis (axSpA, n = 96); group 2: patients with either a positive MRI of the SIJ and no spondyloarthritis features, or a negative MRI of the SIJ but positive human leucocyte antigen-B27 and one spondyloarthritis feature (non-axSpA, n = 38); group 3: patients with unspecified low back pain for > 3 months (control group, n = 82). Complement C3d was measured with double-decker rocket immunoelectrophoresis and evaluated in relation to the group division and baseline findings by SIJ MRI. RESULTS: In total, 184 C3d analyses were performed. The mean ± sd level of C3d was 33.8 ± 8.1 AU/mL. There were no differences in C3d levels between the three patient groups, mean values being: axSpA = 34.3 ± 7.9 AU/mL, non-axSpA = 33.5 ± 6.9 AU/mL, and controls = 33.4 ± 9.2 AU/mL. The level of C3d was not related to MRI findings. CONCLUSIONS: In these patients, complement C3d was not associated with active or structural SIJ changes on MRI suggestive of axial spondyloarthritis.
Asunto(s)
Espondiloartritis Axial , Dolor de la Región Lumbar , Espondiloartritis , Complemento C3d , Estudios Transversales , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Imagen por Resonancia Magnética/métodos , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/patología , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico por imagenRESUMEN
OBJECTIVES: During the past two decades, magnetic resonance imaging (MRI) has increasingly been used diagnostically in axial spondyloarthritis (axSpA), and in 2009 MRI was introduced in the Assessment of SpondyloArthritis Society (ASAS) classification criteria. In clinical practice, there is a risk of overdiagnosis if MRI findings are not related to clinical and biochemical findings. The aim of this study was to provide an estimate of the prevalence of axSpA in a cohort of clinical patients with low back pain and findings suggestive of axSpA according to ASAS through consensus diagnosis at a multi-disciplinary team (MDT) conference, and to describe the performance of the features included in the ASAS criteria. METHOD: Consensus diagnoses of axSpA at MDT conferences were retrospectively established at 3.5 years' follow-up in a cohort of 84 patients, initially referred with disease features according to the ASAS criteria. Patients were examined clinically regarding spondyloarthritis features, and biochemical tests and MRI of the sacroiliac joints and entire spine were performed at baseline and after a mean of 3.5 years. RESULTS: According to the MDT consensus, 25 patients (30%) of the total cohort had axSpA at follow-up; 40% of individuals who fulfilled the ASAS criteria at baseline had axSpA, and 37% at follow-up; 96% of axSpA patients according to the MDT consensus met the ASAS criteria at baseline and 92% at follow-up. CONCLUSION: Approximately one-third of the included patients had axSpA when evaluated at the MDT conference. The ASAS criteria had low predictive value, but high sensitivity at both baseline and follow-up.
Asunto(s)
Espondiloartritis Axial , Espondiloartritis , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Estudios Retrospectivos , Articulación Sacroiliaca/diagnóstico por imagen , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/epidemiologíaRESUMEN
AIMS: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9â10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. RESULTS: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. CONCLUSIONS: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Adulto , Glucemia , Automonitorización de la Glucosa Sanguínea , Estudios Cruzados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Insulina de Acción Prolongada , Persona de Mediana Edad , Factores de RiesgoRESUMEN
STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving â¼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
Asunto(s)
Aborto Espontáneo/epidemiología , COVID-19/complicaciones , Desarrollo Fetal , Medida de Translucencia Nucal/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/virología , Aborto Espontáneo/virología , Adulto , Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Prueba Serológica para COVID-19/estadística & datos numéricos , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/diagnóstico , Primer Trimestre del Embarazo , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Clouds are prevalent and alter PM2.5 mass and chemical composition. Cloud-affected satellite retrievals are often removed from data products, hindering estimates of tropospheric chemical composition during cloudy times. We examine surface fine particulate matter (PM2.5) chemical constituent concentrations in the Interagency Monitoring of PROtected Visual Environments network during Cloudy and Clear Sky times defined using Moderate Resolution Imaging Spectroradiometer (MODIS) cloud flags from 2010-2014 with a focus on differences in particle hygroscopicity and aerosol liquid water (ALW). Cloudy and Clear Sky periods exhibit significant differences in PM2.5 and chemical composition that vary regionally and seasonally. In the eastern US, relative humidity alone cannot explain differences in ALW, suggesting emissions and in situ chemistry exert determining impacts. An implicit clear sky bias may hinder efforts to quantitatively to understand and improve model representation of aerosol-cloud interactions.
RESUMEN
BACKGROUND: The effect of nature-based interventions on self-reported mental well-being in patients with physical disease is gaining increasing attention. However, there is a lack of randomized controlled trials investigating this area. Due to the massive costs in health care systems, there is a need for new strategies to address these issues and an urgent need for attention to this field. Nature-based interventions are low cost, easy to implement, and should get attention within the health care field. Therefore, the objective was to find the impact of nature interventions on mental well-being in humans with a physical disease. METHODS: In four major databases (PubMed, Cinahl, PsycINFO, and Cochrane Library), a systematic review of quantitative studies of nature's impact on self-reported mental health in patients with physical disease was performed. A total of 1909 articles were retrieved but only five met the inclusion criteria and were summarized. RESULTS: All five studies were quantitative, with a control group and a nature-based intervention. A source of heterogeneity was identified: the patients in one of the five studies were psychosomatic. In the four studies with somatic patients, significant benefit of nature on self-reported mental health outcomes was found; the only study that failed to show a significant benefit was the one with psychosomatic patients. CONCLUSION: A significant effect of nature on mental well-being of patients with somatic disease was found. The result in patients with psychosomatic disease is inconclusive, and more studies in this category are needed. Further research on the effect of nature on mental health is merited, with special attention to standardizing intervention type and dose as well as outcome measures within each medical discipline.
Asunto(s)
Salud Mental/estadística & datos numéricos , Naturaleza , Trastornos Psicofisiológicos/psicología , Calidad de Vida/psicología , Adulto , HumanosAsunto(s)
Artritis Reumatoide , Terapia Biológica/psicología , Semántica , Espondilitis Anquilosante , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Barreras de Comunicación , Información de Salud al Consumidor/ética , Información de Salud al Consumidor/métodos , Humanos , Percepción Social , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/psicología , Encuestas y CuestionariosAsunto(s)
Proteínas de Filamentos Intermediarios/genética , Trastornos por Fotosensibilidad/etiología , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Vesícula/etiología , Vesícula/patología , Recuento de Células , Separación Celular , Citocinas/metabolismo , Femenino , Proteínas Filagrina , Citometría de Flujo , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Células de Langerhans/efectos de la radiación , Mutación con Pérdida de Función , Masculino , Monocitos/efectos de la radiación , Trastornos por Fotosensibilidad/patología , Piel/metabolismo , Piel/patología , Pruebas Cutáneas/métodos , Succión/efectos adversosRESUMEN
OBJECTIVES: To investigate whether antibody response patterns against Klebsiella pneumoniae capsular serotypes can discriminate patients with axial spondyloarthritis (axSpA) from patients with non-specific low back pain (LBP). METHOD: Immunoglobulin (Ig)G and IgA antibodies against K. pneumoniae capsular serotypes K2, K26, K36, and K50 were measured, and antibody seropositivity compared between groups and analysed for patient correlation in five different groups: (a) 96 patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA; (b) 38 patients with either a positive magnetic resonance imaging (MRI) scan as defined by ASAS or a positive human leucocyte antigen (HLA)-B27 status plus one clinical SpA feature, characterized as 'non-axSpA'; (c) 82 non-specific LBP patients; (d) 40 healthy blood donors and (e) 43 patients with diagnosed ankylosing spondylitis (AS) served as the negative and positive control groups. RESULTS: There was no difference in IgG and IgA seropositivity against all serotypes between the axSpA, non-axSpA, and LBP groups. No significant correlations were found between anti-Klebsiella antibodies and age, gender, HLA-B27, or high-sensitivity C-reactive protein (hsCRP). IgG seropositivity against K50 was more frequent in AS (25.6%) than in axSpA (13.5%, p < 0.05). axSpA patients with radiographic sacroiliitis and AS controls concordantly had the highest frequency of seropositivity for ≥ 2 serotypes (21%). CONCLUSIONS: The antibody patterns against K. pneumoniae serotypes K2, K26, K36, and K50 did not discriminate between early axSpA and non-specific LBP.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Klebsiella pneumoniae/inmunología , Dolor de la Región Lumbar/inmunología , Sacroileítis/inmunología , Espondiloartropatías/inmunología , Adolescente , Adulto , Cápsulas Bacterianas/inmunología , Proteína C-Reactiva/inmunología , Estudios de Casos y Controles , Dinamarca , Femenino , Antígeno HLA-B27/genética , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Imagen por Resonancia Magnética , Masculino , Sacroileítis/diagnóstico por imagen , Sacroileítis/genética , Serogrupo , Espondiloartropatías/diagnóstico por imagen , Espondiloartropatías/genética , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/inmunología , Adulto JovenRESUMEN
BACKGROUND: Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. PATIENTS AND METHODS: A retrospective single-centre study of 529 patients with stages II-III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after adjusting for PS and comorbidity. RESULTS: Elderly patients (>70â years) had significantly more comorbidity (p<0.001) and poorer PS (p=0.001) than younger patients. Elderly were more frequently treated with single-agent therapy (p=0.001) and at lower initial dose (p<0.001). There was no age-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3-5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality. Elderly patients receiving <50% of planned cycles had shorter DFS (HR=1.78, p=0.020) and higher CRC mortality (HR=2.17, p=0.027) than elderly receiving all cycles. Poor PS in younger and elderly patients was related to shorter DFS (HR=1.95, p=0.002; HR=1.6, p=0.035, respectively) and overall survival (OS; HR=2.28, p<0.001; HR=2.03, p=0.002). Comorbidity in younger patients was significantly related to shorter DFS (HR 2.72, p<0.001), OS (HR 3.16, p<0.001) and higher CRC mortality (HR 2.70, p=0.001). CONCLUSIONS: Choice of regimen, primary dose reduction and given dose intensity in patients treated with adjuvant chemotherapy for CRC were highly dependent on age. However, age had no impact on DFS and CRC mortality. Comorbidity in younger patients and PS in all patients were associated with shorter DFS and higher CRC mortality.
RESUMEN
AIMS: To investigate the long-term efficacy and safety of empagliflozin as add-on to metformin in people with Type 2 diabetes. METHODS: Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double-blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA1c , weight and blood pressure at week 76. RESULTS: Compared with placebo, adjusted mean changes from baseline in HbA1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were -7 mmol/mol [(-0.6%) 95% CI -8, -5 mmol/mol (-0.8, -0.5%); P < 0.001] and -8 mmol/mol [(-0.7%) 95% CI -10, -6 mmol/mol (-0.9, -0.6%); P < 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were -1.9 kg (95% CI -2.5, -1.3; P < 0.001) and -2.2 kg (95% CI -2.8, -1.6; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≤ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. CONCLUSIONS: In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add-on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA1c , weight and systolic blood pressure.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Moduladores del Transporte de Membrana/uso terapéutico , Metformina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Anciano , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/efectos adversos , Índice de Masa Corporal , Terapia Combinada/efectos adversos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Dieta para Diabéticos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Resistencia a Medicamentos , Quimioterapia Combinada/efectos adversos , Ejercicio Físico , Femenino , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Humanos , Hipertensión/complicaciones , Hipertensión/prevención & control , Hipertensión/terapia , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Moduladores del Transporte de Membrana/administración & dosificación , Moduladores del Transporte de Membrana/efectos adversos , Metformina/efectos adversos , Persona de Mediana Edad , Sobrepeso/complicaciones , Sobrepeso/prevención & control , Sobrepeso/terapiaRESUMEN
Hedgehog (Hh) signaling is important for development and homeostasis in vertebrates and invertebrates. Ligand-independent, deregulated Hh signaling caused by loss of negative regulators such as Patched causes excessive cell proliferation, leading to overgrowth in Drosophila and tumors in humans, including basal-cell carcinoma and medulloblastoma. We show that in Drosophila deregulated Hh signaling also promotes cell survival by increasing the resistance to apoptosis. Surprisingly, cells with deregulated Hh activity do not protect themselves from apoptosis; instead, they promote cell survival of neighboring wild-type cells. This non-cell autonomous effect is mediated by Hh-induced Notch signaling, which elevates the protein levels of Drosophila inhibitor of apoptosis protein-1 (Diap-1), conferring resistance to apoptosis. In summary, we demonstrate that deregulated Hh signaling not only promotes proliferation but also cell survival of neighboring cells. This non-cell autonomous control of apoptosis highlights an underappreciated function of deregulated Hh signaling, which may help to generate a supportive micro-environment for tumor development.
Asunto(s)
Apoptosis , Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Animales , Drosophila , Proteínas de Drosophila/genética , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Cinesinas/metabolismo , Ligandos , Neuropéptidos/genética , Neuropéptidos/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Transcripción Genética , Regulación hacia ArribaRESUMEN
To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs), we implanted poly lactic-co-glycolic acid (PLGA) membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye (Brilliant Blue). Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG revealed the white membranes to have a significantly higher P1-amplitude ratio than the blue (P = 0.027), and a correlation between brightness ratio and P1-amplitude ratio was found (r = 0.762). Based on our findings, we conclude that bright subretinal objects can produce normal mfERG amplitude ratios even when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care.
RESUMEN
Biodegradable scaffolds play an important adjunct role in transplantation of retinal progenitor cells (RPCs) to the subretinal space. Poly(ε-Caprolactone) (PCL) scaffolds with different modifications were subretinally implanted in 28 porcine eyes and evaluated by multifocal electroretinography (mfERG) and histology after 6 weeks of observation. PCL Short Nanowire, PCL Electrospun, and PCL Smooth scaffolds were well tolerated in the subretinal space in pigs and caused no inflammation and limited tissue disruption. PCL Short Nanowire had an average rate of preserved overlying outer retina 17% higher than PCL Electrospun and 25% higher than PCL Smooth. Furthermore, PCL Short Nanowire was found to have the most suitable degree of stiffness for surgical delivery to the subretinal space. The membrane-induced photoreceptor damage could be shown on mfERG, but the reductions in P1 amplitude were only significant for the PCL Smooth. We conclude that of the tested scaffolds, PCL Short Nanowire is the best candidate for subretinal implantation.
RESUMEN
An analytical method using HPLC coupled with a charged aerosol detector (CAD) and a mass selective detector (MSD) was developed to characterize the non-ionic surfactant polysorbate 80 (PS 80). The molecular structure and heterogeneous composition due to isomers and various lengths of PEG-chains make it difficult to develop sensitive and specific analytical methods. Hence, there is only limited knowledge about the stability and purity of this compound. Polysorbate 80 does not possess any chromophore, thus UV detection is not applicable. Therefore, CAD and MSD have been used for determination. The aim of this study was to characterize polysorbate 80 and to examine its stability at pH 1.0 and 37 degrees C simulating harsh gastric conditions. It was shown that this surfactant is liable to degradation under these conditions. Within 8 h monoesters of PS 80 were hydrolyzed to an extent of 9.5% (+/- 3.0%), whereas incubation in water did not result in any detectable degradation. Furthermore, we demonstrated that HPLC-MS is a suitable technique to investigate ethoxylated compounds like polysorbates.
Asunto(s)
Aerosoles/análisis , Polisorbatos/análisis , Tensoactivos/análisis , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Espectrometría de Masas , Peso Molecular , Polisorbatos/química , Espectrometría de Masa por Ionización de Electrospray , Tensoactivos/química , UltrasonidoRESUMEN
Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can mitigate many of the neurochemical alterations induced by chronic stress.
Asunto(s)
Encefalinas/biosíntesis , Glutamato Descarboxilasa/biosíntesis , Prosencéfalo/metabolismo , Precursores de Proteínas/biosíntesis , Recompensa , Estrés Psicológico/fisiopatología , Animales , Encefalinas/genética , Masculino , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Long-Evans , Núcleos Septales/metabolismoRESUMEN
A history of limited, intermittent intake of palatable food (sucrose drink) attenuates hypothalamic-pituitary-adrenal (HPA) axis stress responses and induces markers of neuronal plasticity in stress- and reward-regulatory brain regions. Synaptic plasticity could provide a mechanism for long-term changes in neuronal function, implying that sucrose stress-dampening may endure over long periods of time. The present study tests the persistence of HPA axis dampening and plasticity after cessation of palatable drinking. Adult, male Long-Evans rats (n=10-13) with free access to water and chow were given additional twice-daily access to 4ml sucrose (30%) or water for 14days. Rats were subsequently tested for HPA responsiveness to an acute (20min) restraint stress at 1, 6 and 21days after the cessation of sucrose. Brains were collected for immunohistochemical analysis of FosB/deltaFosB, a marker of long-term neuronal plasticity, in the basolateral amygdala (BLA) and nucleus accumbens (NuAc). Prior sucrose consumption significantly decreased the plasma corticosterone response to restraint at 1day after the last palatable drink presentation, and also increased FosB/deltaFosB-positive cells in the BLA and in the NuAc core. This HPA-dampening persisted through 21days after the termination of the palatable drink, as did the increased FosB/deltaFosB immunoreactivity in both the BLA and the NuAc core. These data suggest that chronic palatable food intake causes lasting changes in stress/reward-modulatory circuitry and that the suppressed hormonal response to stress that can persist well beyond periods of palatable drink exposure.
Asunto(s)
Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Estrés Psicológico/tratamiento farmacológico , Sacarosa/administración & dosificación , Edulcorantes/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Corticosterona/sangre , Modelos Animales de Enfermedad , Ingestión de Alimentos/efectos de los fármacos , Masculino , Núcleo Accumbens/metabolismo , Ratas , Ratas Long-Evans , Estrés Psicológico/metabolismo , Estrés Psicológico/patología , Factores de TiempoRESUMEN
Standard practices for indirectly assessing the pasteurization status of milk products are primarily based on the thermal inactivation kinetics of the endogenous milk enzyme, alkaline phosphatase (ALP). This assessment provides an invaluable, if not required, tool for both regulatory and in-house process control and validation. Endogenous milk ALP manifests a slightly higher heat resistance than the pathogenic microflora upon which pasteurization time and temperature requirements are based. Hence, ALP activity is recognized and accepted as the method of choice for the rapid validation of milk product pasteurization. However, ALP assays have notable limitations that must be understood if they are to be administered and interpreted correctly and the results are to be applied judiciously. Issues such as the reactivation of heat-denatured ALP and the presence of both heat-stable and -labile microbial ALP are addressed. A discussion of ALP in the milk of nonbovine species is presented based on the limited literature available. Some discussion of research involving alternative pasteurization indicators also is presented. This article is intended to summarize the pertinent details of the ALP assay for dairy products (noting the basis and limitations of various methods) and the processing, handling, and known compositional factors that influence the assay results.
Asunto(s)
Fosfatasa Alcalina/análisis , Manipulación de Alimentos/métodos , Leche/enzimología , Animales , Industria Lechera/métodos , Leche/normas , Reproducibilidad de los ResultadosRESUMEN
The use of performance- and image-enhancing drugs/substances (PIED) outside elite sports appears to be increasing, although the current knowledge of the nature of PIED use among recreational athletes is scarce. The present study analyzed enquiries that were submitted to the Danish Anti Doping Agency (ADD) over an 18-month period, to gain knowledge of PIED use among individuals who exercise recreationally in Denmark. One thousand three hundred ninety eight queries were examined with respect to the age and gender of the enquirer, affiliation to sport or exercise and substance in question. The key findings were that the ADD information service is generally used by males in their mid-20s who exercise in gyms and are not engaged in competitive sports. Approximately 15% of the enquirers were users of anabolic androgenic steroids (AAS) or other substances banned within elite sports by the World Anti Doping Agency, and an additional 15% considered using such substances. The present results suggest that there is a pronounced interest in the use of AAS and other PIEDs among Danish gym members.