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1.
Neurol Sci ; 36(6): 861-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25555995

RESUMEN

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3'UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10(-4)) and trait anger scores (p = 7.66 × 10(-4)). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Receptores de Dopamina D4/genética , Adulto , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Receptores Dopaminérgicos/genética
2.
Knee Surg Sports Traumatol Arthrosc ; 22(10): 2372-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24985525

RESUMEN

PURPOSE: For deepening trochleoplasty, a procedure used worldwide to correct trochlear dysplasia, only few surgical steps are described precisely. Important surgical landmarks, such as optimal cartilaginous trochlear depth and percentages of the new lateral and medial facet, remain unanswered. METHODS: A cross-sectional study (January 2011-August 2012) was carried out in adult patients (16-35 years) without trochlear dysplasia, who underwent magnetic resonance imaging (MRI). The main outcome was trochlear depth. The secondary outcome was the lateral/medial facet ratio. Measurements were made on the first axial cut from proximal with complete cartilage coverage of the trochlea. Differences between men and women were assessed. RESULTS: Fifty-three patients (70% men) were included. Mean age was 24.6 years (SD±5.5). Overall mean trochlear depth was found to be as 4.0 mm (95% CI 3.6-4.3). Values differed significantly by gender (p=0.0271) with a mean of 3.4 mm (95% CI 3.0-3.8) for women and a mean of 4.2 mm (95% CI 3.8-4.7) for men. The mean ratio between the lateral and medial facet was 1.71 (95% CI 1.62-1.80), the lateral facet contributing 62.6% (95% CI 61.3-63.8) and the medial facet contributing 37.4% (95% CI 36.2-38.7) to the total cartilage length. For the facet ratio, there was no statistically significant gender difference (n.s.). CONCLUSIONS: This study provides data on important landmarks for deepening trochleoplasty based on average MRI measurements in the general population. The difference between the MRI measurement and actual cartilage surface measurement is likely to be minimal, but is yet to be evaluated. Further evaluation of these landmarks by prospectively performing deepening trochleoplasty will determine the value of the clinical implication. LEVEL OF EVIDENCE: II.


Asunto(s)
Cartílago Articular/anatomía & histología , Fémur/anatomía & histología , Articulación de la Rodilla/anatomía & histología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Valores de Referencia , Adulto Joven
3.
Neurosci Biobehav Rev ; 136: 104606, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35289272

RESUMEN

Accumulating scientific and clinical evidence highlighted pathological hyperinflammation as a cardinal feature of SARS-CoV-2 infection and acute COVID-19 disease. With the emergence of long COVID-19 syndrome, several chronic health consequences, including neuropsychiatric sequelae, have gained attention from the public and medical communities. Since inflammatory mediators have also been accredited as putative biomarkers of suicidal ideations and behaviors, hyper- and neuroinflammation might share some colliding points, overlapping and being interconnected in the context of COVID-19. This review aims to provide a summary of current knowledge on the molecular and cellular mechanisms of COVID-19-associated hyper/neuroinflammation with focus on their relevance to the inflammatory hypothesis of suicide development. Subsequently, strategies to alleviate COVID-19 hyper/neuroinflammation by immunomodulatory agents (many of which at experimental stages) as well as psychopharmacologic/psychotherapeutic approaches are also mentioned. While suicide risk in COVID-19 survivors - until now little known - needs further analysis through longitudinal studies, current observations and mechanistic postulates warrant additional attention to this possibly emerging mental health concern.


Asunto(s)
COVID-19 , Suicidio , COVID-19/complicaciones , Humanos , Enfermedades Neuroinflamatorias , SARS-CoV-2 , Ideación Suicida , Síndrome Post Agudo de COVID-19
4.
Eur Respir J ; 38(5): 1127-35, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21540310

RESUMEN

Sarcoidosis is a complex systemic inflammatory disease of unknown aetiology that is influenced by a variety of genetic and environmental factors. To identify further susceptibility loci for sarcoidosis, a genome-wide association study (GWAS) was conducted in 381 patients and 392 control individuals based on Affymetrix 100k GeneChip data. The top 25 single-nucleotide polymorphisms (SNPs) were selected for validation in an independent study panel (1,582 patients versus 1,783 controls). Variant rs10484410 on chromosome 6p12.1 was significantly associated, with a Bonferroni-corrected p-value of 2.90 × 10⁻² in the validation sample and a nominal p-value of 2.64 × 10⁻4 in the GWAS. Extensive fine mapping of the novel locus narrowed down the signal to a region comprising the genes BAG2, C6orf65, KIAA1586, ZNF451 and RAB23. Verification of the sarcoidosis-associated nonsynonymous SNP rs1040461 in a further independent case-control sample and quantitative mRNA expression studies point to the RAB23 gene as the most likely risk factor. RAB23 is proposed to be involved in antibacterial defence processes and regulation of the sonic hedgehog signalling pathway. The identified association of the 6p12.1 locus with sarcoidosis implicates this locus as a further susceptibility factor and RAB23 as a potential signalling component that may open up new perspectives in the pathophysiology of sarcoidosis.


Asunto(s)
Cromosomas Humanos Par 6/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Sarcoidosis/genética , Mapeo Cromosómico , Predisposición Genética a la Enfermedad/genética , Humanos , Desequilibrio de Ligamiento , Proteínas de Unión al GTP rab/genética
5.
Unfallchirurg ; 114(1): 35-40, 2011 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-21161154

RESUMEN

The 2008 European Football Championship 2008 (Euro 08) is the largest sporting event ever organized in Switzerland. One million visitors came to the city of Berne during the event and the local airport in Bern/Belp registered 261 extra flights. For each football game there were 33,000 fans in the stadium and 100,000 fans in the public viewing zones.The ambulance corps and the Department of Emergency Medicine (ED) at Inselspital, University Hospital Berne, were responsible for basic medical care and emergency medical management. Injuries and illnesses were analyzed by a standardized score (NACA score). The preparation strategy as well as costs and patient numbers are presented in detail.A total of 30 additional ambulance vehicles were used, 4,723 additional working days (one-third medical professionals) were accumulated, 662 ambulance calls were registered and 240 persons needed medical care (62% Swiss, 28% Dutch and 10% other nationalities). Among those needing treatment 51 were treated in 1 of the 4 city hospitals. No injuries with NACA grades VI and VII occurred (NACA I: 4, NACA II: 17, NACA III: 16, NACA IV: 10 and NACA V: 4 patients). The city of Berne compensated the Inselspital Bern with a total of 112,603 Euros for extra medical care costs. The largest amount was spent on security measures (50,300 Euros) and medical staff (medical doctors 22,600 Euros, nurses 29,000 Euros). Because of the poor weather and the exemplary behavior of the fans, the course of events was rather peaceful.


Asunto(s)
Medicina de Desastres/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Fútbol Americano/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Heridas y Lesiones/terapia , Aniversarios y Eventos Especiales , Medicina de Desastres/economía , Servicios Médicos de Urgencia/economía , Europa (Continente) , Humanos , Suiza/epidemiología , Heridas y Lesiones/economía
6.
New Phytol ; 187(3): 819-30, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20497351

RESUMEN

*Continuous stem radius changes (DR) include growth and water-related processes on the individual tree level. DR is assumed to provide carbon turnover information complementary to net ecosystem productivity (NEP) which integrates fluxes over the entire forest ecosystem. Here, we investigated the unexpectedly close relationship between NEP and DR and asked for causalities. *NEP (positive values indicate carbon sink) measured by eddy covariance over 11 yr was analysed at three time scales alongside automated point dendrometer DR data from a Swiss subalpine Norway spruce forest. *On annual and monthly scales, the remarkably close relationship between NEP and DR was positive, whereas on a half-hourly scale the relationship was negative. Gross primary production (GPP) had a similar explanatory power at shorter time scales, but was significantly less correlated with DR on an annual scale. *The causal explanation for the NEP-DR relationship is still fragmentary; however, it is partially attributable to the following: radial stem growth with a strong effect on monthly and annual increases in NEP and DR; frost-induced bark tissue dehydration with a parallel decrease in both measures on a monthly scale; and transpiration-induced DR shrinkage which is negatively correlated with assimilation and thus with NEP on a half-hourly scale.


Asunto(s)
Ecosistema , Picea/anatomía & histología , Tallos de la Planta/anatomía & histología , Árboles/anatomía & histología , Microclima , Noruega , Lluvia , Análisis de Regresión , Comunicaciones por Satélite , Estaciones del Año , Suiza , Temperatura , Factores de Tiempo
7.
Lipids Health Dis ; 8: 35, 2009 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-19689798

RESUMEN

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)gamma is a key regulator in adipose tissue. The rare variant Pro12Ala of PPARgamma2 is associated with a decreased risk of insulin resistance. Being dietary PPARgamma ligands, conjugated linoleic acids (CLAs) received considerable attention because of their effects on body composition, cancer, atherosclerosis, diabetes, obesity and inflammation, although some effects were only demonstrated in animal trials and the results in human studies were not always consistent. In the present study effects of CLA supplementation on genome wide gene expression in adipose tissue biopsies from 11 Ala12Ala and 23 Pro12Pro men were investigated. Subjects underwent four intervention periods (4 wk) in a randomized double blind cross-over design receiving 4.25 g/d of either cis-9, trans-11 CLA, trans-10,cis-12 CLA, 1:1 mixture of both isomers or a reference linoleic acid oil preparation. After each intervention biopsies were taken, whole genome expression microarrays were applied, and genes of interest were verified by realtime PCR. RESULTS: The following genes of lipid metabolism were regulated by CLA: LDLR, FASN, SCD, FADS1 and UCP2 were induced, while ABCA1, CD36 and CA3 were repressed. Transcription factors PPARgamma, NFAT5, CREB5 and EBF1, the adipokine NAMPT, members of the insulin signaling cascade SORBS1 and IGF1 and IL6ST were repressed, while the adipokine THBS1 and GLUT4 involved in insulin signaling were induced. Compared to trans-10,cis-12 CLA and the CLA mixture the cis-9, trans-11 CLA isomer exerted weaker effects. Only CD36 (-1.2 fold) and THBS1 (1.5 fold) were regulated. The CLA effect on expression of PPARgamma and leptin genes depends on the PPARgamma2 genotype. CONCLUSION: The data suggest that the isomer specific influence of CLA on glucose and lipid metabolism is genotype dependent and at least in part mediated by PPARgamma. TRIAL REGISTRATION: http://www.controlled-trials.com: ISRCTN91188075.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ácidos Linoleicos Conjugados/farmacología , PPAR gamma/genética , Polimorfismo Genético/genética , Anciano , delta-5 Desaturasa de Ácido Graso , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
Br J Sports Med ; 43(13): 1020-5, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19846420

RESUMEN

OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled multicentre survey of injured and non-injured alpine skiers. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND METHODS: All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. RESULTS: Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.


Asunto(s)
Esquí/lesiones , Adulto , Traumatismos en Atletas/etiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equipos de Seguridad/estadística & datos numéricos , Factores de Riesgo , Suiza , Tiempo (Meteorología) , Adulto Joven
9.
Genes Immun ; 9(2): 103-14, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18216864

RESUMEN

Immunosenescence is characterized by a quantitative decline of adequate immune responses, which renders the elderly individual particularly susceptible to bacterial, viral and fungal pathogens. Whereas changes of the aging adaptive immune system (for example, reduced immunoglobulin secretion) have been extensively characterized, alterations of the innate immune system are still poorly understood. The aim of the present study was to systematically examine mRNA expression levels of innate immune genes and proinflammatory cytokines in peripheral and intestinal leukocytes of subjects of different ages. In both, whole blood samples and in colonic biopsies most of the Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain-like receptors (NLRs) transcript levels were significantly downregulated in elderly subjects (90-99 years). Older individuals, when compared to the younger, exhibited an increased expression and/or secretion of proinflammatory cytokines by peripheral and intestinal leukocytes as well as an increased level of nuclear factor-kappaB activation in colonic biopsies. The observed downregulation of TLRs and NLRs during the aging process may contribute to the lack of effective recognition of invading pathogens or the commensal flora. This effect results in aberrant secondary immune cell activation and could significantly contribute to morbidity and mortality at advanced age.


Asunto(s)
Senescencia Celular/genética , Senescencia Celular/inmunología , Colon/inmunología , Perfilación de la Expresión Génica , Inmunidad Innata/genética , Leucocitos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Colon/citología , Colon/metabolismo , Citocinas/biosíntesis , Citocinas/sangre , Citocinas/genética , Femenino , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/inmunología , Humanos , Inmunidad Celular/genética , Leucocitos/citología , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Receptores Toll-Like/biosíntesis , Receptores Toll-Like/sangre , Receptores Toll-Like/genética
10.
Genes Immun ; 9(3): 240-8, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18340362

RESUMEN

Crohn's disease (CD) and ulcerative colitis (UC) are subforms of inflammatory bowel diseases (IBD). Genetic and environmental factors influencing the onset and course of the diseases have been recently identified. This study uses a two-step approach to detect genes involved in the pathogenesis of IBD by microarray analysis and real-time PCR (RT-PCR). In a first step, microarray expression screening was used to obtain tumour necrosis factor-alpha (TNF-alpha) induction profiles of two human cell lines to represent the tissue cell types involved in IBD. In a second step, a subset of differentially expressed genes was examined by real-time PCR in intestinal biopsy samples of normal controls (NC) compared with UC and CD patients, as well as to a cohort of patients suffering from intestinal diseases other than IBD. Data were obtained from 88 CD, 88 UC, 53 non-IBD patients (inflammatory control), DC and 45 NC individuals. The experimental design enabled the identification of disease-specific expressed genes. DnaJ (Hsp40) homologue, subfamily B, member 5 (DNAJB5) was downregulated in intestinal biopsy samples of the UC cohort compared with NC. A difference in JUNB expression levels was observed by comparing biopsy samples from inflamed and non-inflamed areas of UC patients. Transcript expression differences between IBD and control cohorts were found by examining histamine N-methyltransferase (HNMT), interleukin-1A (IL-1A) and proplatelet basic protein (PPBP) expression. The experimental procedure represents an approach to identify disease-relevant genes, which is applicable to any disease where appropriate model systems are available.


Asunto(s)
Cromosomas Humanos Par 4/genética , Regulación de la Expresión Génica , Enfermedades Inflamatorias del Intestino/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Cartilla de ADN/genética , Femenino , Proteínas del Choque Térmico HSP40/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Interleucina-1alfa/metabolismo , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , beta-Tromboglobulina/metabolismo
11.
Br J Sports Med ; 42(1): 55-8, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17562746

RESUMEN

OBJECTIVE: To analyse the epidemiological data, injury pattern, clinical features and mechanisms of severe spinal injuries related to alpine skiing and snowboarding. STUDY DESIGN: A six-year review of all adult patients with severe spinal injuries sustained from alpine skiing or snowboarding. SETTING: Tertiary trauma centre in Bern, Switzerland. PATIENTS AND METHODS: All adult patients (over 16 years of age) admitted to a tertiary trauma centre from 1 July 2000, through 30 June 2006, were reviewed using a computerised database. From these records, a total of 728 patients injured from snow sports were identified. Severe spinal injuries (defined as spinal fractures, subluxations, dislocations or concomitant spinal cord injuries) were found in 73 patients (17 female, 56 male). The clinical features of these patients were reviewed with respect to epidemiological factors, mechanism of injury, fracture pattern, and neurological status. RESULTS: The majority of severe spinal injuries (n = 63) were related to skiing. Fatal central-nervous injuries and transient or persistent neurological symptoms occurred in 28 patients (23 skiers, 5 snowboarders). None of the snowboarders suffered from persistent neurological sequelae. Snowboarders with severe spinal injuries (n = 10) were all male (p<0.05), and were significantly younger than skiers (p<0.001). The most commonly affected site was the lumbar spine. However, 39 patients (53.4%) suffered from injury pattern at two or more levels. CONCLUSIONS: With advances in technology and slope maintenance, skiers and snowboarders progress to higher skill levels and faster speeds more rapidly than ever before. Great efforts have been focused on reducing extremity injuries in snow sports, but until recently very little attention has been given to spinal injury prevention on the slopes. Suggestions for injury prevention include the use of spine protectors, participation on appropriate runs for ability level, proper fit and adjustment of equipment, and taking lessons with the goal of increasing ability and learning hill etiquette.


Asunto(s)
Esquí/lesiones , Traumatismos Vertebrales/epidemiología , Prevención de Accidentes/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Equipos de Seguridad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Traumatismos Vertebrales/prevención & control , Suiza/epidemiología
12.
Chirurg ; 79(6): 555-9, 2008 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-18458798

RESUMEN

The skin plays an important role in the human immune system, working as a barrier to pathologic influences. A chronic wound breaks that barrier and eliminates that function. Affected patients can suffer from significant reductions in quality of life and become socially isolated. The inability to work may have serious economic consequences for the individual and the community. Treating these wounds with novel, evidence-based techniques can accelerate wound healing while reducing the length of in- and outpatient treatment and thereby the overall costs. This article discusses current and future treatment options in wound conditioning, therapy, and regeneration.


Asunto(s)
Heridas y Lesiones/terapia , Enfermedad Crónica , Predicción , Humanos , Ciencia del Laboratorio Clínico/tendencias , Terapia de Presión Negativa para Heridas/instrumentación , Investigación/tendencias , Cicatrización de Heridas/fisiología , Infección de Heridas/etiología , Infección de Heridas/terapia , Heridas y Lesiones/etiología
13.
Oncogene ; 25(28): 3973-81, 2006 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-16474845

RESUMEN

Pancreatic cancer exhibits profound chemoresistance resulting either from pre-existing (intrinsic) mechanisms, or from anticancer drug treatment itself (acquired chemoresistance). To identify molecular alterations leading to acquired chemoresistance, the chemosensitive pancreatic carcinoma cell line PT45-P1 was exposed to low-dose treatment with etoposide for 6 weeks. Afterwards, these cells (PT45-P1res) were much more resistant to high-dose treatment with anticancer drugs than parental cells. Among several differentially expressed genes in PT45-P1res cells, IL-1beta was most significantly upregulated, a finding in line with our previous observation that IL-1beta accounts for intrinsic chemoresistance of pancreatic carcinoma cells. Elevated IL-1beta expression in PT45-P1res cells was confirmed by real-time PCR and ELISA, and treatment with the IL-1 receptor antagonist restored drug-induced apoptosis. The increased IL-1beta secretion was accompanied by an elevated formation of nitric oxide (NO) and a NO-dependent inhibition of the etoposide-induced caspase-3/-7/-8/-9 activity. Caspase activation was restored either by the iNOS inhibitor 1400W, the reducing agent dithiothreitol or the IL-1 receptor antagonist, resulting in greater sensitivity towards anticancer drug treatment. Conversely, IL-1beta or the NO-donor SNAP decreased caspase activation and apoptosis in etoposide-treated PT45-P1 cells. These data confirm IL-1beta and NO as determinants of chemoresistance in pancreatic cancer, and indicate that the intrinsic and acquired chemoresistance rely to some extent on common molecular targets beneficial for improved therapeutical strategies.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Caspasas , Resistencia a Antineoplásicos , Interleucina-1/metabolismo , Óxido Nítrico/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Western Blotting , Caspasas/metabolismo , Activación Enzimática , Ensayo de Inmunoadsorción Enzimática , Humanos , FN-kappa B/biosíntesis , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa
14.
Psychiatry Res Neuroimaging ; 269: 54-61, 2017 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-28938222

RESUMEN

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD.


Asunto(s)
Ira/fisiología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/genética , Cerebro/diagnóstico por imagen , Cerebro/fisiología , Proteínas del Tejido Nervioso/genética , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Corteza Prefrontal/diagnóstico por imagen
15.
Oecologia ; 54(1): 14-22, 1982 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28310986

RESUMEN

Potted Pinus montana seedlings, age 4 years, transplanted on adjacent east and north facing slopes 25 m apart at alpine timberline (2,020 m a.s.l.) were measured for net photosynthesis and transpiration under ambient conditions using climatised Koch-Siemens cuvettes. Concurrent recordings were made of air temperature, atmospheric water vapour pressure deficit and illuminance at each site.On a typical summers day the northern aspect averaged 9% less light, 1.8°C cooler air temperatures and 25% lower v.p.d. levels than the eastern aspect. The order of these differences was found to increase in the autumn. Net photosynthetic rates of seedlings on the northern aspect were on average 28% lower than the rates of seedlings on the warmer eastern aspect. Differences in transpiration rates were even greater with north slope seedlings averaging rates 42% lower than east slope seedlings.Maximum CO2 uptake rate per hour of east slope seedlings was 3.2 mg CO2 g-1 d.w.h-1 but average rates when light was not limiting were around 2.0 mg CO2 g-1 d.w.h-1. Corresponding values for the north slope seedlings were 3.0 mg CO2 and 1.8 mg CO2 g-1 d.w.h.-1 respectively.Light intensities below 10 klx, when photosynthesis was strongly limited by light, totalled 48% of available daylight hours on the east slope and more than 50% on the north slope.Net photosynthesis was largely unaffected by air temperature between 10°C and the recorded maximum at either site (24°C east, 20°C north) and there was no apparent response to v.p.d. at levels up to 10 mbar. However the consistently higher net photosynthesis of east slope seedlings under all combinations of weather conditions indicated a possible acclimatisation of seedlings at each site.

16.
Oecologia ; 64(2): 284-286, 1984 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28312352

RESUMEN

Clonal stock (grafts of 15-, 50-, and 100-year-old trees) of spruce (Picea abies (L.) Karst.) and fir (Abies alba Mill.) was exposed either to 150 ppb ozone (∼300 µgm-3) during 9 daylight hours or to carbon-filtered air on 35 days between 29 August and 21 October 1983. At the end of the fumigation the trees did not exhibit any visible signs of injury. Transpiration and leaf conductance in light and darkness, measured with a Licor porometer, revealed, however, stomatal sluggishness and - in spruce-increased transpiration.

17.
Tree Physiol ; 21(9): 561-9, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11390300

RESUMEN

Internal water reserves in bark and foliage of trees contribute to transpiration (T) and play an essential role in optimizing water transport by buffering extreme peaks of water consumption. We examined patterns of stem shrinkage and their relationship to tree water dynamics. We measured fluctuations in root radius and stem radius at different stem heights, T of twigs at the top of the crown and sap flow velocities in stem sections of mature subalpine Norway spruce (Picea abies (L.) Karst.) trees over 2 years. The output of each sensor was coupled by physical functions to a mechanistic flow and storage model of tree water relations. The data verified the model-predicted lag in water storage depletion in response to the onset of transpiration and the lag increased with increasing distance from the crown periphery. Between the crown and stem base, the delay ranged from a few minutes to several hours, depending on microclimatic conditions and tree water status. Stem volume changes were proportional to the amount of water exchanged between the elastic tissues of the bark and the rigid xylem, indicating that the "peristaltic" wave of stem contraction along the flow path represented depletion of water stored in bark. On a daily basis, stems lost between 0.2 and 0.5% of their volume as a result of bark dehydration, corresponding to about 2 to 5 l of water. This water contributed directly to T. According to the model based on hydraulic principles, there are three main components underlying the dynamics of water storage depletion: flow resistance, storage capacities of needles and bark, and T of each tree section. The resistances and capacities were proportional to the response delay, whereas T in the lower parts of the tree was inversely proportional. The pattern of T within the crown depended on water intercepted by the branches. Because of these weather-dependent factors, there was no time constant for the response delay along the flow path. Nevertheless, the upper crown and the root section tended to have longer response delays per meter of flow path than the stem. The diurnal course of stem radius fluctuations represents the sum of all external and internal conditions affecting tree water relations; stem radius fluctuations, therefore, provide a sensitive measure of tree water status.


Asunto(s)
Picea/fisiología , Tallos de la Planta/fisiología , Árboles/fisiología , Picea/anatomía & histología , Tallos de la Planta/anatomía & histología , Suiza , Árboles/anatomía & histología , Agua/fisiología
18.
Tree Physiol ; 21(12-13): 869-77, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11498334

RESUMEN

Internal water reserves are depleted and replenished daily, not only in succulent plants, but also in trees. The significance of these changes in tissue water storage for tree water relations was investigated by monitoring diurnal fluctuations in stem radius. In 6-year-old potted Norway spruce (Picea abies (L.) Karst.) trees, whole-tree transpiration rate (T), sap flow at the stem base and fluctuations in stem radius were measured at 10-min intervals over eight successive weeks. The dynamics of diurnal water storage in relation to the daily course of water movement was simulated and the contribution of stored water to T quantified. The finding that, in P. abies, the course of bark water content is linearly coupled to stem radius fluctuations provided the basis for linking stem radius changes to a functional flow and storage model for tree water relations. This model, which consists of physical functions only and is driven by a single input variable (T), accurately simulates the diurnal course of changes in stem radius and water storage of the tree crown and stem. It was concluded that fluctuations were mainly determined by the course of transpiration. The availability of soil water and the degree to which storage tissues were saturated were also factors affecting the diurnal course of stem radius changes. Internally stored water contributed to daily transpiration even in well-watered trees, indicating that stored water plays an important role not only during periods of drought, but whenever water transport occurs within the tree. Needle and bark water reserves were most heavily depleted during transpiration. Together they supplied approximately 10% of daily T on sunny days, and up to 65% on cloudy days. On a daily basis, the crown (mainly needles) contributed approximately eight times more water to T than the stem (mainly bark). The depletion of the two storage pools and the water movements observed in the trees always occurred in the same sequence. In the morning, T first caused a depletion of the water stored in the crown. It then caused depletion of bark storage tissues at ever increasing distances from the needles. Up to 75% of the transpired water could be withdrawn from storage tissues when the increase in T reached a maximum.


Asunto(s)
Ritmo Circadiano/fisiología , Tallos de la Planta/fisiología , Árboles/fisiología , Modelos Biológicos , Picea/fisiología , Transpiración de Plantas/fisiología , Agua/fisiología
19.
Tree Physiol ; 22(15-16): 1125-36, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12414372

RESUMEN

We used local microclimatic conditions and twig sap flow rates to interpret midday stomatal closure in the canopies of two 250-year-old Norway spruce (Picea abies (L.) Karst.) trees at a subalpine site in the Swiss Alps (1,650 m a.s.l.). Both trees showed midday stomatal closure on most clear summer days, despite the permanently wet soil. We used a modified Penman-Monteith formula to simulate potential transpiration of single twigs (ET(T)) based on high-resolution temporal and spatial microclimate data obtained both inside and outside the crowns. Comparison of calculated ET(T) values and measured twig sap flow rates enabled us to pinpoint the occurrence of midday stomatal closure and the microclimatic conditions present at that time. We found that vapor pressure deficit (and for upper-crown twigs, ET(T)) largely explained the timing of initial midday stomatal closure but gave no explanation for the different patterns of stomatal behavior after initial closure in upper- and lower-crown twigs. After the initial stomatal closure, upper-crown twigs maintained high transpiration rates by continuously regulating stomatal aperture, whereas stomatal aperture decreased rapidly in lower-crown twigs and did not increase later in the day. Midday stomatal closure in lower-crown twigs occurred on average 1 h later than in upper-crown twigs. However, the microclimate at the time of initial stomatal closure was similar at both crown locations except that lower-crown twigs received significantly less solar radiation than upper-crown twigs both at the time of initial stomatal closure and afterwards. High rates of sap flow in twigs did not always lead to stomatal closure and therefore could not explain the phenomenon. We conclude that stomatal conductance can be modeled accurately only when both local microclimatic conditions and tree water status are known. Further, we hypothesize that both the quantity and quality of light play an important role in the reopening of closed stomata during the day.


Asunto(s)
Picea/fisiología , Transpiración de Plantas/fisiología , Árboles/fisiología , Biomasa , Clima , Humedad , Hojas de la Planta/fisiología , Suiza , Temperatura , Factores de Tiempo
20.
Environ Pollut ; 109(3): 415-22, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15092874

RESUMEN

Ozone (O(3)) flux into Norway spruce (Picea abies) and cembran pine (Pinus cembra) needles was estimated under ambient conditions at six rural sites between 580 and 1950 m a.s.l. We also assessed age-related differences in O(3) flux by examining changes in leaf conductance across the life span of Norway spruce. At the leaf level O(3) flux into the needles was effectively controlled by stomatal conductance and, hence by factors such as temperature, irradiance and humidity, which control stomatal conductance. Seasonal variations in O(3) flux were mainly attributed to the course of the prevailing temperature. During the growing season, however, data have emphasised leaf-air vapour pressure difference as the environmental factor most likely to control stomatal conductance and O(3) flux into the needles. In the sun crown stomatal conductance averaged over the growing season decreased with increasing tree age from 42.0+/-3.5 mmol O(3) m(-2) s(-1) in 17-year-old trees to 7.1+/-1.0 mmol O(3) m(-2) s(-1) in 216-year-old trees, indicating that O(3) concentration in the substomatal cavities is higher in young than in old trees. Independent from tree age stomatal conductance and O(3) flux were approximately 50% lower in shade needles as compared to sun-exposed needles. Stomatal conductance was also greater in the current flush (24+/-5.6 mmol O(3) m(-2) s(-1)) and in 1-year old needles (16+/-4 mmol O(3) m(-2) s(-1)) than in older needle age classes (12+/-1 mmol O(3) m(-2) s(-1), averaged across the four older needle age classes). In trees similar in age (60-65 years old) average O(3) flux into sun needles increased from 0.55+/-0.36 nmol m(-2) s(-1) at the valley floor to 0.9 nmol m(-2) s(-1) in 1950 m a.s.l. Cumulative O(3) uptake during the vegetation period increased from 11.4+/-1.7 mol m(-2) in the valley to 14 mol m(-2) at the alpine timberline. Although stomatal conductance provides the principal limiting factor for O(3) flux, additional field research is necessary in order to improve our understanding concerning the quantitative 'physiological threshold dose' which internally can be active and can have adverse effects of O(3) on forest trees.

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