Dexamethasone and RU24858 induce survival and growth factor receptor bound protein 2, leukotriene B4 receptor 1 and annexin-1 expression in primary human neutrophils

Glucocorticoids are widely used anti-inflammatory medication in diseases like asthma and chronic obstructive pulmonary disease. Glucocorticoids can either activate (transactivation) or inhibit (transrepression) transcription. RU24858 was introduced as a dissociated glucocorticoid and it has been reported to transrepress but not to transactivate. The aim of this study was to compare the effects of RU24858 and dexamethasone in human neutrophils. RU24858 delayed spontaneous neutrophil apoptosis and further enhanced GM-CSF- induced neutrophil survival to a similar extent as dexamethasone. Like dexamethasone RU24858 also reduced CXCL8 and MIP-1α. Unexpectedly however, RU24858 increased the expression of the glucocorticoid-inducible genes BLT-1, Annexin-1 and Grb-2 in neutrophils to a similar level as seen with dexamethasone. We have shown here that dexamethasone and RU24858 both increase Grb-2, BLT1 and Annexin-1 expression and inhibit CXCL8 and MIP-1α production. This suggests that RU24858 was not able to dissociate between transactivation and transrepression in human neutrophils but enhanced neutrophil survival. © the author(s), publisher and licensee Libertas Academica Ltd

Metabolism of [14C]GA19 and [14C]GA53 by ecotypes of Betula pendula: the role of photoperiod

In many temperate woody species, short days (SDs) induced growth cessation has been shown to be prevented by the application of gibberellins (GAs). Evidence has also been forwarded for the influence of photoperiod on the metabolism of applied GAs. Continuing with this line of research, we studied the metabolism of 14C-labelled GA19 and GA53. [14C]GA19 and [14C] A53 were applied to the apices of the northern ecotype (67º N) and to the leaves of the southern ecotype (64º N) of Betula pendula Roth. under different photoperiods and at different times in order to compare metabolism during day and night periods. Assay of metabolites was made 10 h after application. Less than half of each applied GA was taken in by the plants and most of the activity was recovered from the application points. There was no clear effect of photoperiod on uptake of the GAs. After the HPLC analysis, most of the absorbed radiolabelled GAs were eluted as unmetabolised forms. However, significant levels of gibberellins A20, A29, A1, and A8 were recovered as metabolites of [14C]GA19 both in apical stems and leaves. In 1SD and 4SD-treated plants, there was less metabolism of [14C]GA19 compared to LD-treated plants. The difference was due to reduced metabolism of 14C]GA19 by SD-treated plants during the night period. On the other hand, metabolism of [14C]GA53 was very limited in all day-length treatments and during both, day and night periods. The most abundant metabolite was [14C]GA19 (10% of the activity in the samples). Key words/phrases: Conjugation, ecotype, gibberellins, metabolism, radioactivity SINET: Ethiopian Journal of Science Vol. 28 (1) 2005: 33–4

Rautarikastepellettien pelkistyskokeen herkkyysanalyysi:lämpötilan vaikutus pelkistymisnopeuteen

Tiivistelmä. Työn tavoitteena oli tutkia, miten rautarikastepelletille suoritettavan pelkistyskokeen tuloksiin vaikuttavat mahdolliset poikkeamat koeolosuhteissa. Tässä työssä arvioitiin, kuinka mahdolliset lämpötilan muutokset vaikuttavat rautarikastepelletin pelkistysnopeuteen. Työ tehtiin yhteistyössä SSAB:n Raahen terästehtaan kanssa. Työssä käytetyt valmiiksi analysoidut rautarikastepelletit toimitettiin SSAB:n Raahen terästehtaalta. Pelletit esikäsiteltiin magneettierottimella, koska kokeisiin haluttiin mahdollisimman ei magneettisia pellettejä. Esikäsittelyn jälkeen valittiin vielä vähiten magnetiittia sisältävistä pelleteistä kokeissa käytettävät pelletit. Rautarikastepelleteistä valmistetaan rautaa masuuneissa, jotka ovat suuria tuotantolaitoksia. Suurin osa masuunissa valmistetusta raakaraudasta käytetään teräksen valmistukseen. Masuunit tuottavat raakarautaa pelkistysreaktioilla monta tonnia vuorokaudessa. Työn kokeet suoritettiin Oulun yliopiston laboratoriossa olevalla TG-uunilla. Kokeissa käytettävien pellettien tuli olla kooltaan ja muodoltaan mahdollisimman identtisiä. Nämä pelletit valittiin pelleteistä, jotka olivat vähiten magnetiittisia. Työhön liittyen suoritettiin kolme pelkistyskoetta, joista ensimmäinen oli referenssikoe. Referenssikokeeseen verrattiin kahta seuraavaa koetta, joihin lämpötilaa muutettiin +20 ℃:n ja -20 ℃:n verran. Kokeiden tuloksista tehtiin kaksi kuvaajaa, joissa on esitetty massanmuutoskäyrät. Massanmuutoskäyristä nähtiin lämpötilamuutos verrattuna referenssiajon massanmuutoskäyrään. Tulimme siihen tulokseen, että lämpötilanmuutoksella ei ole merkitystä rautarikastepelletin pelkistysnopeuteen. Lämpötilan nosto vaikutti jonkin verran tuloksiin

Beyond rest and quiescence (endodormancy and ecodormancy) : A novel model for quantifying plant-environment interaction in bud dormancy release

Bud dormancy of plants has traditionally been explained either by physiological growth arresting conditions in the bud or by unfavourable environmental conditions, such as non-growth-promoting low air temperatures. This conceptual dichotomy has provided the framework also for developing process-based plant phenology models. Here, we propose a novel model that in addition to covering the classical dichotomy as a special case also allows the quantification of an interaction of physiological and environmental factors. According to this plant-environment interaction suggested conceptually decades ago, rather than being unambiguous, the concept of "non-growth-promoting low air temperature" depends on the dormancy status of the plant. We parameterized the model with experimental results of growth onset for seven boreal plant species and found that based on the strength of the interaction, the species can be classified into three dormancy types, only one of which represents the traditional dichotomy. We also tested the model with four species in an independent experiment. Our study suggests that interaction of environmental and physiological factors may be involved in many such phenomena that have until now been considered simply as plant traits without any considerations of effects of the environmental factors.Peer reviewe

Modeling with history-dependent Petri nets

Most information systems that are driven by process models (e.g., workflow management systems) record events in event logs, also known as transaction logs or audit trails. We consider processes that not only keep track of their history in a log, but also make decisions based on this log. Extending our previous work on history-dependent Petri nets we propose and evaluate a methodology for modelling processes by such nets and show how history-dependent nets can combine modelling comfort with analysability

Duty of Notification and Aviation SafetyA Study of Fatal Aviation Accidents in the United States in 2015

After the Germanwings accident, the French Safety Investigation Authority (BEA) recommended that the World Health Organization (WHO) and European Community (EC) develop clear rules for the duty of notification process. Aeromedical practitioners (AMEs) face a dilemma when considering the duty of notification and conflicts between pilot privacy and public and third-party safety. When balancing accountability, knowledge of the duty of notification process, legislation and the clarification of a doctor's own set of values should be assessed a priori. Relatively little is known of the magnitude of this problem in aviation safety. To address this, the National Transportation Safety Board (NTSB) database was searched to identify fatal accidents during 2015 in the United States in which a deceased pilot used a prescribed medication or had a disease that potentially reduced pilot performance and was not reported to the AME. Altogether, 202 finalized accident reports with toxicology were available from (the year) 2015. In 5% (10/202) of these reports, the pilot had either a medication or a disease not reported to an AME which according to the accident investigation was causal to the fatal accident. In addition, the various approaches to duty of notification in aviation in New Zealand, Finland and Norway are discussed. The process of notification of authorities without a pilot's express permission needs to be carried out by using a guidance protocol that works within legislation and professional responsibilities to address the pilot and the public, as well as the healthcare provider. Professional guidance defining this duty of notification is urgently needed.Peer reviewe

Продукты ограниченного протеолиза: подходы к обнаружению и диагностические возможности в оценке тяжести патологии при эндогенной интоксикации

ПРОДУКТЫ ОГРАНИЧЕННОГО ПРОТЕОЛИЗАПРОТЕИНАЗО-ИНГИБИТОРНАЯ СИСТЕМАОТРАВЛЕНИЕ /ДИАГН /ОСЛЭНДОГЕННАЯ ИНТОКСИКАЦИЯ /ДИАГН /ОСЛСРЕДНЕМОЛЕКУЛЯРНАЯ ПЕПТИДНАЯ ФРАКЦИЯПАТОЛОГИЧЕСКИЕ ПРОЦЕССЫЛАБОРАТОРНЫЕ МЕТОДЫ И ПРОЦЕДУРЫБЕЛКОВО-ПЕПТИДНЫЕ КОМПОНЕНТ

Women with PCOS have an increased risk for cardiovascular disease regardless of diagnostic criteria - a prospective population-based cohort study

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with many cardiovascular disease (CVD) risk factors, such as obesity, type 2 diabetes mellitus and hypertension. However, it remains debatable whether the presence of multiple CVD risk factors translates to increased CVD events. DESIGN: A prospective, population-based Northern Finland Birth Cohort 1966. METHODS: Individuals with an expected date of birth in 1966 in Northern Finland have been followed from birth. Women in the cohort were classified as having PCOS according to either the National Institute of Health (NIH) criteria (n = 144) or the Rotterdam criteria (n = 386) at age 31, and they were compared to women without any PCOS features. The study population was re-examined at age 46, and the incidence of major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke, heart failure and cardiovascular mortality, was recorded up to age 53. RESULTS: During the 22-year follow-up, both women with NIH-PCOS and women with Rotterdam-PCOS had a significantly higher risk for cardiovascular events than control women. The BMI-adjusted hazard ratio (HR) for MACE in the Rotterdam-PCOS group and the NIH-PCOS group was 2.33 (1.26-4.30) and 2.47 (1.18-5.17), respectively. The cumulative hazard curves in both diagnostic categories began to diverge at age 35. Regarding the individual CVD endpoints, MI was significantly more prevalent in both women with NIH-PCOS (P = .010) and women with Rotterdam-PCOS (P = .019), when compared to control women. CONCLUSIONS: PCOS should be considered a significant risk factor for CVD. Future follow-up will show how the risk of CVD events develops after menopausal age

Redo ventral rectopexy : is it worthwhile?

Background Minimally invasive ventral mesh rectopexy (VMR) is a widely used surgical treatment for posterior pelvic organ prolapse; however, evidence of the utility of revisional surgery is lacking. Our aim was to assess the technical details, safety and outcomes of redo minimally invasive VMR for patients with external rectal prolapse (ERP) recurrence or relapsed symptoms of internal rectal prolapse (IRP). Methods This is a retrospective cohort study of patients with recurrent ERP or symptomatic IRP who underwent redo minimally invasive VMR between 2011 and 2016. The study was conducted at three hospitals in Finland. Data collected retrospectively included patient demographics, in addition to perioperative and short-term postoperative findings. At follow-up, all living patients were sent a questionnaire concerning postoperative disease-related symptoms and quality of life. Results A total of 43 redo minimally invasive VMR were performed during the study period. The indication for reoperation was recurrent ERP in 22 patients and relapsed symptoms of IRP in 21 patients. In most operations (62.8%), the previously used mesh was left in situ and a new one was placed. Ten (23.3%) patients experienced complications, including 2 (4.7%) mesh-related complications. The recurrence rate was 4.5% for ERP. Three patients out of 43 were reoperated on for various reasons. One patient required postoperative laparoscopic hematoma evacuation. Patients operated on for recurrent ERP seemed to benefit more from the reoperation. Conclusions Minimally invasive redo VMR appears to be a safe and effective procedure for treating posterior pelvic floor dysfunction with acceptable recurrence and reoperation rates.Peer reviewe

Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils

BACKGROUND: Granulocytes are important in the pathogenesis of several inflammatory diseases. Apoptosis is pivotal in the resolution of inflammation. Apoptosis in malignant cells is induced by histone deacetylase (HDAC) inhibitors, whereas HDAC inhibitors do not usually induce apoptosis in non-malignant cells. The aim of the present study was to explore the effects of HDAC inhibitors on apoptosis in human eosinophils and neutrophils. METHODS: Apoptosis was assessed by relative DNA fragmentation assay, annexin-V binding, and morphologic analysis. HDAC activity in nuclear extracts was measured with a nonisotopic assay. HDAC expression was measured by real-time PCR. RESULTS: A HDAC inhibitor Trichostatin A (TSA) induced apoptosis in the presence of survival-prolonging cytokines interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF) in eosinophils and neutrophils. TSA enhanced constitutive eosinophil and neutrophil apoptosis. Similar effects were seen with a structurally dissimilar HDAC inhibitor apicidin. TSA showed additive effect on the glucocorticoid-induced eosinophil apoptosis, but antagonized glucocorticoid-induced neutrophil survival. Eosinophils and neutrophils expressed all HDACs at the mRNA level except that HDAC5 and HDAC11 mRNA expression was very low in both cell types, HDAC8 mRNA was very low in neutrophils and HDAC9 mRNA low in eosinophils. TSA reduced eosinophil and neutrophil nuclear HDAC activities by ~50-60%, suggesting a non-histone target. However, TSA did not increase the acetylation of a non-histone target NF-κB p65. c-jun-N-terminal kinase and caspases 3 and 6 may be involved in the mechanism of TSA-induced apoptosis, whereas PI3-kinase and caspase 8 are not. CONCLUSIONS: HDAC inhibitors enhance apoptosis in human eosinophils and neutrophils in the absence and presence of survival-prolonging cytokines and glucocorticoids