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1.
Proc Biol Sci ; 288(1944): 20202770, 2021 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-33563118

RESUMEN

Studies increasingly show that social connectedness plays a key role in determining survival, in addition to natural and anthropogenic environmental factors. Few studies, however, integrated social, non-social and demographic data to elucidate what components of an animal's socio-ecological environment are most important to their survival. Female giraffes (Giraffa camelopardalis) form structured societies with highly dynamic group membership but stable long-term associations. We examined the relative contributions of sociability (relationship strength, gregariousness and betweenness), together with those of the natural (food sources and vegetation types) and anthropogenic environment (distance from human settlements), to adult female giraffe survival. We tested predictions about the influence of sociability and natural and human factors at two social levels: the individual and the social community. Survival was primarily driven by individual- rather than community-level social factors. Gregariousness (the number of other females each individual was observed with on average) was most important in explaining variation in female adult survival, more than other social traits and any natural or anthropogenic environmental factors. For adult female giraffes, grouping with more other females, even as group membership frequently changes, is correlated with better survival, and this sociability appears to be more important than several attributes of their non-social environment.


Asunto(s)
Jirafas , Animales , Ambiente , Femenino , Alimentos , Factores Sociológicos
2.
J Synchrotron Radiat ; 27(Pt 1): 60-66, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31868737

RESUMEN

A new Rococo 2 X-ray fluorescence detector was implemented into the cryogenic sample environment at the Hard X-ray Micro/Nano-Probe beamline P06 at PETRA III, DESY, Hamburg, Germany. A four sensor-field cloverleaf design is optimized for the investigation of planar samples and operates in a backscattering geometry resulting in a large solid angle of up to 1.1 steradian. The detector, coupled with the Xspress 3 pulse processor, enables measurements at high count rates of up to 106 counts per second per sensor. The measured energy resolution of ∼129 eV (Mn Kα at 10000 counts s-1) is only minimally impaired at the highest count rates. The resulting high detection sensitivity allows for an accurate determination of trace element distributions such as in thin frozen hydrated biological specimens. First proof-of-principle measurements using continuous-movement 2D scans of frozen hydrated HeLa cells as a model system are reported to demonstrate the potential of the new detection system.


Asunto(s)
Espectrometría por Rayos X/instrumentación , Sincrotrones , Calcio/análisis , Cloruros/análisis , Criopreservación , Electrodos , Diseño de Equipo , Células HeLa/química , Humanos , Fósforo/análisis , Potasio/análisis , Compuestos de Silicona , Espectrometría por Rayos X/métodos , Azufre/análisis , Rayos X
3.
Mediators Inflamm ; 2020: 9501617, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32508528

RESUMEN

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are immunologically mediated processes caused by hypersensitivity reaction accompanied by similar features including lymphocytic alveolitis and granuloma formation. Recent studies describe the role of TREM receptors in T cell activation, differentiation, and granuloma formation. Alveolar macrophages activation via TREM receptors may be the key factor mediating subsequent immune response. The aim of the study was to analyse TREM-1 and TREM-2 expression to identify further molecular mechanisms participating in the immunopathogenesis of sarcoidosis and HP. METHODS: Flow cytometry was performed to analyse TREM-1 and TREM-2 expression on CD14+ cells in bronchoalveolar lavage fluid from patients having sarcoidosis or HP and a control group. RESULTS: The study proved increased TREM-1 expression on alveolar macrophages in pulmonary sarcoidosis and diminished TREM-1 expression in HP-Sarcoidosis: median: 76.7; HP: median: 29.9; control: median: 53.3, (sarcoidosis versus HP: p < 0.001; sarcoidosis versus control: p < 0.05). TREM-2 expression was increased in both, sarcoidosis and HP-sarcoidosis: median: 34.79; HP: median: 36.00; control: median: 12.98, (sarcoidosis versus control: p < 0.05; HP versus control: p < 0.05). Correlation analysis showed negative correlation between TREM-1 and total number of CD8+ cytotoxic T cells. In sarcoidosis TREM-1 expression decreased with changes of HRCT image, decrease in CD4/CD8 ratio and decrease in DLCO. CONCLUSIONS: Differences in TREM receptor expression in sarcoidosis (increase in TREM-1 and TREM-2) and HP (increase in TREM-2) and correlation analysis suggests that activation via TREM may participate in typical immunological characteristics of sarcoidosis and HP.


Asunto(s)
Líquido del Lavado Bronquioalveolar , Receptores de Lipopolisacáridos/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Sarcoidosis Pulmonar/metabolismo , Linfocitos T/inmunología , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Adulto , Anciano , Neoplasias Encefálicas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Glioma/metabolismo , Humanos , Sistema Inmunológico , Inflamación , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Modelos de Riesgos Proporcionales
4.
Org Biomol Chem ; 17(9): 2467-2478, 2019 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-30747188

RESUMEN

The neuropeptide Y (NPY) Y4 receptor is a G protein coupled receptor, which is targeted by pancreatic polypeptide, a homologue of NPY. Selective Y4R agonists were suggested as potential therapeutics for the treatment of obesity. Highly potent dimeric peptidic Y4R agonists, constituting two pentapeptide moieties connected through an aliphatic linker, represent an interesting class of Y4R ligands. Based on this compound class, photoresponsive Y4R ligands, containing an azobenzene, azopyrazole, diethienylethene or a fulgimide chromophore were prepared to explore structural requirements of such Y4R agonists on Y4R binding. The synthesized Y4R ligands, containing a non-aliphatic rigid photochromic linker, switch reversibly in aqueous buffer and exhibited high Y4R affinity throughout. This demonstrated that the replacement of the highly flexible aliphatic linker by a considerably less flexible photochromic linker was well tolerated with respect to Y4R binding. Differences in Y4R affinity and activity between the individual photoisomers (varying in spatial orientation and flexibility) were marginal suggesting that the linking element in the dimeric ligands is less critical for the adaptation of high-affinity binding modes at the receptor.


Asunto(s)
Compuestos Cromogénicos/química , Compuestos Cromogénicos/farmacología , Oligopéptidos/química , Oligopéptidos/farmacología , Receptores de Neuropéptido Y/metabolismo , Animales , Compuestos Azo/química , Compuestos Azo/farmacología , Células CHO , Cricetulus , Humanos , Ligandos , Unión Proteica , Receptores de Neuropéptido Y/agonistas , Relación Estructura-Actividad
5.
Br J Dermatol ; 179(6): 1358-1367, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30192389

RESUMEN

BACKGROUND: To prevent infections that arise from the skin surface it is necessary to decolonize human skin prior to any proposed treatment or surgical intervention. Photodynamic inactivation of bacteria (PIB) uses cationic photosensitizers that attach to the surface of bacteria, generate reactive oxygen species on light irradiation and thereby kill bacteria via oxidative mechanisms. OBJECTIVES: To evaluate the potential and the safety of PIB for decolonization of bacteria from skin. METHODS: PIB with the new photosensitizer SAPYR [2-((4-pyridinyl)methyl)-1H-phenalen-1-one chloride] was initially tested against different bacterial species in vitro. Then, ex vivo porcine skin samples were used as a model for decolonization of different bacteria species. The numbers of viable bacteria were quantified and the mitochondrial activity of skin cells was histologically analysed (using nitroblue tetrazolium chloride, NBTC). The same procedure was performed for human skin and meticillin-resistant Staphylococcus aureus (MRSA). RESULTS: The in vitro studies showed a 5 log10 reduction of all tested bacterial species. On ex vivo porcine skin samples, PIB reduced the viability of all tested bacterial species by at least 3 log10 steps. On human skin samples ex vivo, PIB reduced the number of viable MRSA by maximal 4·4 log10 steps (1000 µmol L-1 SAPYR, incubation time 10 min, 60 J cm-2 ). NBTC staining showed normal mitochondrial activity in skin cells after all PIB modalities. CONCLUSIONS: The results of this study show that PIB can effectively and safely kill bacteria like MRSA on the skin surface and might have the potential of skin decolonization in vivo.


Asunto(s)
Desinfección/métodos , Staphylococcus aureus Resistente a Meticilina/efectos de la radiación , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Piel/microbiología , Administración Cutánea , Animales , Recuento de Colonia Microbiana , Humanos , Resistencia a la Meticilina/efectos de los fármacos , Resistencia a la Meticilina/efectos de la radiación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación , Fotoquimioterapia/efectos adversos , Fármacos Fotosensibilizantes/efectos adversos , Piel/citología , Piel/efectos de la radiación , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Porcinos
6.
Photochem Photobiol Sci ; 17(8): 1056-1067, 2018 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-29915828

RESUMEN

We report the synthesis and the spectroscopic and electrochemical properties of six mononuclear iridium(iii) and ruthenium(ii) complexes bearing S,S'-extended phenanthroline ligands. Starting from 5,6-dibromide-1,10-phenanthroline, the dithiine derivatives N,N'-1,10-phenanthrolinedithiino[2,3-b]quinoxaline and N,N'-1,10-phenanthrolinedithiino[2,3-b]benzene were prepared by primary N,N'-complexation of the dibromo derivative and subsequent nucleophilic substitution at the complex. The photoluminescence of the phenanthroline-dithiine containing complexes shows distinctively increased lifetimes for all Ir(iii) and Ru(ii) complexes. The activity of the series of Ir(iii) and Ru(ii) complexes as photosensitizers in visible-light photocatalytic water reduction is demonstrated by dihydrogen evolution with a [Fe3(CO)12] catalyst and triethylamine as a sacrificial donor.

7.
Epidemiol Infect ; 147: e58, 2018 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-30501684

RESUMEN

Although the impact of diarrhoeal disease on paediatric health in Nigeria has decreased in recent years, it remains an important cause of morbidity and mortality in children under 5 years. Rotavirus is recognised as an important aetiological agent, but information on the contribution of intestinal protozoa to watery diarrhoea in this age group in Nigeria is scarce. In this cross-sectional study, faecal samples from children admitted to healthcare centres in Abakaliki, Nigeria with acute watery diarrhoea (N = 199) and faecal samples from age-matched controls (N = 37) were examined for Cryptosporidium and Giardia using immunofluorescent antibody testing and molecular methods. Cryptosporidium was identified in 13 case samples (6.5%) and no control samples. For three samples, molecular characterisation indicated C. hominis, GP60 subtypes IaA30R3, IaA14R3 and IdA11. Giardia was not detected in any samples. This contrast in prevalence between the two intestinal protozoa may reflect their variable epidemiologies and probably differing routes of infection. Given that these two parasitic infections are often bracketed together, it is key to realise that they not only have differing clinical spectra but also that the importance of each parasite is not the same in different age groups and/or settings.

8.
J Viral Hepat ; 24(10): 840-849, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28342229

RESUMEN

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.


Asunto(s)
Anilidas/administración & dosificación , Carbamatos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Compuestos Macrocíclicos/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Uracilo/análogos & derivados , 2-Naftilamina , Adulto , Anciano , Anilidas/efectos adversos , Carbamatos/efectos adversos , Estudios de Cohortes , Ciclopropanos , Quimioterapia Combinada , Femenino , Genotipo , Alemania , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Humanos , Lactamas Macrocíclicas , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , Prolina/análogos & derivados , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversos , Valina , Carga Viral
9.
Eur J Clin Microbiol Infect Dis ; 36(10): 1955-1964, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28560472

RESUMEN

Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late-onset sepsis in neonates. The question is whether neonates acquire endemic hospital-adapted clones or incidentally occurring CoNS strains after birth during their hospital stay. Therefore, a prospective study was performed on the prevalence of CoNS in the stool of babies (born vaginally or by cesarean section) during their first days of life. Their clonal relatedness and potential to induce invasive disease were characterized. CoNS were analyzed from the stool samples of newborns with a load of CoNS above 103 colony-forming units (CFU)/mL. The identification of CoNS was performed phenotypically and genotypically. For typing, repetitive polymerase chain reaction (PCR), pulsed-field gel electrophoresis, and multilocus sequence typing were used. Resistance profiles, biofilm production, the presence of icaAD and of IS256 were determined as well. From a total of 207 stool samples (56 newborns), CoNS were detected in 41% of the newborns, mostly on day 3 for the first time (62.5%). Staphylococcus epidermidis was isolated in 85.7% of cases, harbored no IS256 element, and mostly expressed no biofilm. The isolates were separated into four main clusters by repetitive sequence-based PCR. 24% of the strains showed no antimicrobial resistance. 20% were resistant against four antibiotics of two different antibiotic classes. The remaining strains were resistant only against one antimicrobial substance class. Thus, it can be concluded that newborns do not acquire hospital-adapted endemic, multidrug-resistant S. epidermidis isolates during their first days of life. Yet, the results support the thesis that, during hospital stay, environmental parameters may convert sensible/noninvasive S. epidermidis strains into multidrug-resistant strains with characteristics of invasiveness.


Asunto(s)
Genotipo , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/aislamiento & purificación , Factores de Virulencia/análisis , Carga Bacteriana , Técnicas de Tipificación Bacteriana , Heces/microbiología , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Tipificación Molecular , Prevalencia , Estudios Prospectivos , Staphylococcus epidermidis/patogenicidad
10.
Acta Psychiatr Scand ; 136(6): 571-582, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28722128

RESUMEN

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.


Asunto(s)
Trastorno Bipolar/epidemiología , Radiación Electromagnética , Internacionalidad , Estaciones del Año , Adolescente , Adulto , África/epidemiología , Edad de Inicio , Asia/epidemiología , Australia/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Sistema Solar , América del Sur/epidemiología , Luz Solar , Adulto Joven
11.
Org Biomol Chem ; 15(22): 4882-4896, 2017 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-28537315

RESUMEN

Histone deacetylases (HDACs) play a crucial role in numerous biological processes and therefore are targeted in anticancer research and in the field of epigenetics. Dithienylethenes (DTEs) and fulgimides were functionalized with hydroxamic acids, which is a known moiety binding to zinc dependent HDACs, to gain photoswitchable HDAC inhibitors. The new DTE based inhibitors showed moderate photochromic properties in polar solvents and the inhibitory activity changes up to a factor of four. The photochromic performance of the prepared fulgimide inhibitors was very good, even in aqueous buffer. They achieved a maximum three-fold difference in inhibitory activity. Docking experiments using the crystal structures of the tested enzymes gave a rationale for the observed moderate differences in the activities of the inhibitors.


Asunto(s)
Etilenos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Indoles/farmacología , Succinimidas/farmacología , Tiofenos/farmacología , Relación Dosis-Respuesta a Droga , Etilenos/síntesis química , Etilenos/química , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Indoles/síntesis química , Indoles/química , Estructura Molecular , Procesos Fotoquímicos , Relación Estructura-Actividad , Succinimidas/síntesis química , Succinimidas/química , Tiofenos/síntesis química , Tiofenos/química
12.
J Evol Biol ; 28(1): 54-64, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25494878

RESUMEN

The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that--for the first time--allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes.


Asunto(s)
Fertilización/fisiología , Haplotipos , Preferencia en el Apareamiento Animal/fisiología , Ratones , Animales , Femenino , Fertilización/genética , Tamaño de la Camada , Masculino
13.
Org Biomol Chem ; 13(40): 10198-204, 2015 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-26303394

RESUMEN

Flavin derivatives with an extended π-conjugation were synthesized in moderate to good yields from aryl bromides via a Buchwald-Hartwig palladium catalyzed amination protocol, followed by condensation of the corresponding aromatic amines with violuric acid. The electronic properties of the new compounds were investigated by absorption and emission spectroscopy, cyclic voltammetry, density functional theory (DFT) and time dependent density functional theory (TDDFT). The compounds absorb up to 550 nm and show strong luminescence. The photoluminescence quantum yields ϕPL measured in dichloromethane reach 80% and in PMMA (poly(methyl methacrylate)) 77%, respectively, at ambient temperature. The electrochemical redox behaviour of π-extended flavins follows the mechanism previously described for the parent flavin.


Asunto(s)
Flavinas/química , Flavinas/síntesis química , Electrones , Estructura Molecular , Oxidación-Reducción , Teoría Cuántica
14.
Psychol Med ; 44(3): 507-17, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23721695

RESUMEN

BACKGROUND: Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD). METHOD: To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts. RESULTS: The non-Li group had smaller hippocampal volumes than the controls or the Li group (F 2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t(51) = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t(43) = 2.62, corrected p = 0.02). CONCLUSIONS: Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.


Asunto(s)
Antimaníacos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Compuestos de Litio/farmacología , Fármacos Neuroprotectores/farmacología , Adulto , Análisis de Varianza , Antimaníacos/uso terapéutico , Trastorno Bipolar/patología , Estudios de Casos y Controles , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Hipocampo/patología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Entrevista Psicológica , Compuestos de Litio/uso terapéutico , Imagen por Resonancia Magnética/métodos , Masculino , Fármacos Neuroprotectores/uso terapéutico , Estudios Prospectivos , Recurrencia , Factores de Tiempo , Resultado del Tratamiento
15.
Org Biomol Chem ; 12(20): 3175-80, 2014 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-24722623

RESUMEN

Catalytic hydrolysis of peptides, proteins, phosphates or carboxylate esters in nature is catalysed by enzymes, which are efficient, fast and selective. Most of the hydrolytic chemical catalysts published so far mimic the active site of enzymes and contain metal complexes and amino acid residues. Their synthesis can be laborious, while the hydrolytic activity is still limited compared to enzymes. We present an approach that uses fluid membranes of vesicles and micelles as a support for amphiphilic additives, which cooperatively cleave aryl ester bonds. The membrane anchored bis-Zn(II)-complex 1 is hydrolytically active and hydrolyses fluorescein diacetate (FDA) with a second order rate constant (k2) of 0.9 M(-1) s(-1). The hydrolytic activity is modulated by co-embedded membrane additives, bearing common amino acid side chain functional groups. With this approach, the hydrolytic activity of the system is enhanced up to 16 fold in comparison with cyclen 1 (k2 = 14.7 M(-1) s(-1)). DOPC and DSPC lipids form at room temperature fluid or gel phase membranes, respectively. Omitting the lipid, micellar solutions were obtained with hydrolytic activity reaching k2 = 13.4 M(-1) s(-1). It is shown that cooperative hydrolysis is favoured in fluid membranes and micelles, allowing the active moieties to arrange freely. The embedding and dynamic self-assembly of membrane active components in fluid membranes and micelles provide facile access to hydrolytically active soft interfaces.


Asunto(s)
Ésteres/química , Membranas Artificiales , Micelas , Fluoresceína/química , Transferencia Resonante de Energía de Fluorescencia , Hidrólisis , Cinética , Fosfatidilcolinas/química , Fosfolípidos/química , Rodaminas/química , Soluciones , Propiedades de Superficie , Tensoactivos/química
16.
Unfallchirurg ; 116(11): 1006-14, 2013 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-23949195

RESUMEN

BACKGROUND: The basis for the classification of acetabular fractures depends on accurate radiological diagnostics. The use of conventional X-rays alone implicates a low intrapersonal reproducibility and interpersonal reliability. By applying computed tomography (CT) at an early stage in the emergency room, the typical diagonal X-rays of ala and obturator, on which the classification is based, are no longer recommended. The aim of this study was to develop a new reliable classification system based on standardized CT slices according to the system of Judet and Letournel without using diagonal X-rays. MATERIALS AND METHODS: In this study 12 select cases with acetabular fractures were peer reviewed. In each case eight characteristic CT slices (five axial, two coronal and one sagittal) were selected as well as the conventional anteroposterior X-ray of the pelvis. All cases were peer reviewed by 14 members of the "AG Becken" (working group pelvis). The classification of the acetabular fractures was based on Judet and Letournel and the results were compared with the reference classification. The results were scaled according to differences to the original classification and the relevance to the approach as well as the medical qualification of the member. RESULTS: A total of 167 out of 168 possible classifications were conducted, 90 cases (54 %) were in accordance with the reference classification. In 69 cases (41 %) the outcome was different, which would have had no influence on the choice of the surgical approach. A wrong classification was present eight times (5 %). According to the medical qualification status the senior physicians were right in 54%, the residents in 53 %. Within the group of senior physicians 7.5 % of the classifications were completely wrong and 93 % of the participating members would have preferred to have more CT slices. CONCLUSION: The CT-based classification developed represents an adaption to the current standard of diagnostics of acetabular fractures and represents a step towards simplification of the classification. It is suitable to estimate the correct surgical approach and the behavior of the fracture. For an accurate classification and the association to one of the fracture types in the system of Judet and Letournel more slices and 3D reconstructions (MPR) are necessary.


Asunto(s)
Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Algoritmos , Puntos Anatómicos de Referencia/diagnóstico por imagen , Fracturas Óseas/clasificación , Fracturas Óseas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Índices de Gravedad del Trauma , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
17.
Unfallchirurg ; 116(4): 351-64; quiz 365-6, 2013 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-23515647

RESUMEN

The demographic changes in society automatically lead to an increase in specific diseases and injuries in the older generation. Therefore, the proportion of osteoporotic and fatigue fractures increases in total and also the absolute number of insufficiency fractures of the pelvic ring. In younger people pelvic ring fractures are mostly due high speed trauma. In the elderly this often occurs by low energy trauma or even with no trauma which is then designated as insufficiency fracture. The problematic of such fractures is insufficiently covered in the conventional classification. Conventional radiological diagnostics must often be supplemented by slice imaging procedures. The therapy forms must be more closely adapted to the general condition and physical health of the patient than by classical fractures and the substantially reduced sustainability of osteosynthesis in altered bones must be taken into consideration.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/cirugía , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/cirugía , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Fijación Interna de Fracturas/instrumentación , Humanos , Huesos Pélvicos/diagnóstico por imagen , Radiografía
18.
Clin Exp Allergy ; 42(1): 76-84, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22092824

RESUMEN

BACKGROUND: Recently, it has been established that pollen grains contain Th2-enhancing activities besides allergens. OBJECTIVE: The aim of this study was to analyse whether pollen carry additional adjuvant factors like microbes and what immunological effects they may exert. METHODS: Timothy pollen grains were collected and disseminated on agar plates, and the growing microorganisms were cultivated and defined. Furthermore, the immunologic effects of microbial products on DC and T cell responses were analysed. RESULTS: A complex mixture of bacteria and moulds was detected on grass pollen. Besides Gram-negative bacteria that are known to favour Th1-directed immune responses, moulds were identified as being sources of allergens themselves. Herein, we focused on Gram-positive bacteria that were found in high numbers, e.g. Bacillus cereus and Bacillus subtilis. Contact of immature dendritic cells (DC) from grass pollen allergic donors with supernatants of homogenized Gram-positive bacteria induced maturation of DC as measured by up-regulation of CD80, CD83 and CD86 and by enhanced production of IL-6, IL-12p40 and TNF-α, which was less pronounced compared with effects induced by lipopolysaccharide (LPS). Consequently, stimulation of autologous CD4(+) T cells with supernatants of homogenized Gram-positive bacteria plus grass pollen allergen-pulsed DC led to an enhanced proliferation and production of IL-4, IL-13, IL-10, IL-17, IL-22 and IFN-γ production compared with T cells that were stimulated with allergen-pulsed immature DC alone, whereas production of the transcription factor for regulatory T cells FoxP3 was not significantly affected. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that grass pollen is colonized by several microorganisms that influence the immune response differently. Similar to LPS, supernatants of homogenized Gram-positive bacteria may serve as adjuvants by augmenting DC maturation and inflammatory Th1, Th2 and Th17 responses helping to initiate allergic immune responses.


Asunto(s)
Bacterias Grampositivas/inmunología , Inflamación/inmunología , Activación de Linfocitos/inmunología , Phleum/microbiología , Polen/microbiología , Rinitis Alérgica Estacional/inmunología , Adyuvantes Inmunológicos , Bacillus cereus/inmunología , Bacillus cereus/aislamiento & purificación , Bacillus subtilis/inmunología , Bacillus subtilis/aislamiento & purificación , Diferenciación Celular , Medios de Cultivo , Células Dendríticas/citología , Células Dendríticas/inmunología , Citometría de Flujo , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Phleum/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/fisiopatología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología
19.
Br Poult Sci ; 53(4): 431-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23130577

RESUMEN

1. The effects of n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acids (CLA) on genes involved in carnitine homeostasis were compared in laying hens. Three groups of laying hens were fed on a control diet or a diet with either 3% of fish oil or CLA for 4 weeks. 2. Feed intake and egg production rate did not differ between the three groups. Diets with fish oil or CLA had only a weak effect on mRNA levels of PPARα target genes (ACO, CPT-I) in the liver and did not influence mRNA concentrations of the most important carnitine transporter OCTN2, enzymes of involved in carnitine synthesis (TMLD, TMABA-DH, BBD) or concentrations of carnitine in plasma, liver and total egg contents. 3. Hens fed the CLA diet had lower concentrations of free and total carnitine in egg yolk but higher concentrations of carnitine in albumen than control hens (P < 0·05), whereas the amount of free and total carnitine in whole egg did not differ. 4. In conclusion, the study showed that feeding fish oil or CLA causes only a weak activation of PPARα in tissues of laying hens that probably explained the lack of effect on carnitine homeostasis. The results contrast with those in humans and mice that show a significant effect of synthetic PPARα agonists on carnitine homeostasis in humans and mice.


Asunto(s)
Carnitina/metabolismo , Pollos/fisiología , Suplementos Dietéticos/análisis , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Ácidos Linoleicos Conjugados/administración & dosificación , PPAR alfa/metabolismo , Alimentación Animal/análisis , Animales , Transporte Biológico , Carnitina/biosíntesis , Pollos/genética , Dieta/veterinaria , Femenino , Hígado/enzimología , Especificidad de Órganos , PPAR alfa/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Espectrometría de Masas en Tándem/veterinaria , Regulación hacia Arriba
20.
J Eur Acad Dermatol Venereol ; 25(11): 1340-5, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21349116

RESUMEN

BACKGROUND: Tattooing entails the injection of high amounts of colourants into skin. Excepting black inks, red azo pigments are the most frequent colourant used. Part of the pigment is transported away via lymphatic system. Another part can be decomposed in skin, which might be responsible for many known adverse skin reactions. OBJECTIVE: The aim of this study was to estimate the extent of decomposition and transportation by measuring the decrease of pigment concentration in human skin under in vivo conditions. METHODS: Red pigments were extracted from nine tattooed skin specimen and attempted quantification by using HPLC technology. To optimize quantification, we synthesized five common red azo pigments with purity at 98% and used them as HPLC reference substances. RESULTS: In five of the nine skin specimens, we were able to identify and subsequently to quantify the red tattoo pigments such as Pigment Red 22 or Pigment Red 112. The mean pigment concentration in skin was 0.077 ± 0.046 mg/cm². As the pigment concentration in skin ranges from 0.60 to 9.42 mg/cm² (mean: 2.53) directly after tattooing, we estimate a decrease of 87 to 99% of pigment concentration in skin after tattooing. CONCLUSION: Millions of people have many and large tattoos, whereas a single tattoo frequently covers a skin area of more than 300 cm². Thus, the major part of more than 760 mg of azo pigments either decomposes in skin or migrates in the body. That may pose a health risk on tattooed individuals, in particular may cause severe skin reactions.


Asunto(s)
Color , Tatuaje , Cromatografía Líquida de Alta Presión , Humanos
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