Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis

Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide. We found that both cibinetide and EPO ameliorated the clinical course of experimental colitis in mice, resulting in improved weight gain and survival. Correspondingly, DSS-exposed mice treated with cibinetide or EPO displayed preserved tissue integrity due to reduced infiltration of myeloid cells and diminished production of pro-inflammatory disease mediators including cytokines, chemokines and nitric oxide synthase-2. Experiments using LPS-activated primary macrophages revealed that the anti-inflammatory effects of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF-κB subunit p65 activity. Cibinetide activation of the IRR exerts potent anti-inflammatory effects, especially within the myeloid population, reduces disease activity and mortality in mice. Cibinetide thus holds promise as novel disease-modifying therapeutic of inflammatory bowel disease

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Measurement of associated W plus charm production in pp collisions at √s=7 TeV

Peer reviewe

Intraventricular pressure in non-communicating hydrocephalus patients before endoscopic third ventriculostomy

In patients with non-communicating hydrocephalus impairment of cerebral compliance can occur pre- but also intraoperatively

How bispectral index compares to spectral entropy of the EEG and A-line ARX index in the same patient

Bispectral index (BIS) monitoring of depth of anesthesia has pioneered the field for more recent monitoring devices like the A-line ARX Index (AAI) or the state (SE) and response entropy (RE) monitoring devices. Following an observational design the present study aimed to simultaneously compare in the same patient recorded BIS, AAI and entropy values

Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression

BACKGROUND/AIMS: Adipocytokines play a key role in the pathophysiology of non-alcoholic fatty liver diseases (NAFLD). Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic and immune processes. METHODS: We prospectively examined the effect of weight loss on systemic levels and/or hepatic expression of adiponectin/adiponectin receptors, leptin/leptin receptors, resistin and PBEF/Nampt/visfatin. Severely obese patients underwent laparoscopic adjustable gastric banding (LABG) and serum samples (n=30) were collected before, and after 6 and 12 months. Paired liver biopsies (before and 6 months after LABG) were obtained from 18 patients. RESULTS: Bariatric surgery improved insulin resistance, abnormal liver function tests and liver histology. Pronounced weight loss after 6 and 12 months was accompanied by a significant increase in serum adiponectin levels whereas both leptin and PBEF/Nampt/visfatin levels decreased. Resistin serum levels increased after 6 months but fell below baseline values after 12 months. Liver mRNA expression of adiponectin increased slightly after 6 months whereas leptin mRNA expression did not change. Interestingly, weight loss resulted in a significant decrease of hepatic mRNA expression of resistin, PBEF/Nampt/visfatin and both leptin receptor isoforms while expression of type 1 and 2 adiponectin receptor was not affected. Liver immunohistochemistry performed on index and follow-up liver biopsies revealed an increase in adiponectin staining, showed no effect on resistin/leptin positivity, and demonstrated a decrease in PBEF/Nampt/visfatin immunoreactivity. CONCLUSIONS: Weight loss after LABG surgery drives the adipocytokine milieu towards a more anti-inflammatory direction both systemically and in the liver