The effect of malotilate, a derivative of malotilate and a flavenoid on eicosanoid production in inflammatory bowel disease in rats

Acetic acid induced colitis in rats was used to investigate the effects of malotilate, a drug which has been shown to inhibit 5-1ipoxygenase in human macrophages, the malotilate derivate ZY16268 and the flavenoid ZY16369 on the eicosanoid production and the colonic morphology in inflammatory bowel disease. Acetic acid produced an acute inflammatory response in the colon, associated with a markedly raised inflammation score (15.8 vs. < 0.5), based on a seven-scaled scoring system which includes observation of haemorrhage, submucosal oedema, cellular infiltration, goblet cell depletion, loss of architecture, crypt abscesses and serosal involvement, of which every item was subdivided as mild, moderate and severe. Incubation of colonic mucosa from rats treated with arachidonic acid and stimulated with A23187 showed an increase of the cyclooxygenase product 12-hydroxy-heptadecatrienoic acid (HHT) and the 12-1ipoxygenase product (12-HETE) and a decrease in the formation of 6-keto-prostaglandin F1α(6kPGF1α) in comparison with normal rat mucosa. Malotilate, ZY16268 and ZY16369 all resulted in a decrease in HHT, leukotriene B4 (LTB4)-like compounds and 12-hydroxyeicosaenoic acid (12-HETE) production. None of the tested compounds significantly reduced the colonic damage by acetic acid although the formation of 12-HETE was proportional to the histologically obtained inflammation score. There were marked differences in eicosanoid formation patterns between rat and human mucosa, both normal and inflamed. In view of the hyperacute nature of the mucosal damage and the marked differences in eicosanoid production, acetic acid induced colitis in rats is probably not a suitable model of ulcerative colitis in humans

Free initial wave packets and the long-time behavior of the survival and nonescape probabilities

The behavior of both the survival S(t) and nonescape P(t) probabilities at long times for the one-dimensional free particle system is shown to be closely connected to that of the initial wave packet at small momentum. We prove that both S(t) and P(t) asymptotically exhibit the same power-law decrease at long times, when the initial wave packet in momentum representation behaves as O(1) or O(k) at small momentum. On the other hand, if the integer m becomes greater than 1, S(t) and P(t) decrease in different power-laws at long times.Comment: 4 pages, 3 figures, Title and organization changed, however the results not changed, To appear in Phys. Rev.

Scanning Electron Microscopy Study of Biofilms on Silicone Voice Prosthesis

Patients after laryngectomy often receive silicone made voice prostheses fot speech rehabilitation. The prosthesis is inserted in a shunt between the trachea and the digestive tract. As the prosthesis is placed in a nonsterile environment it becomes rapidly colonized by microorganisms eventually leading to failure and frequent exchange of the implant. In this study, explanted Groningen Button silicone voice prostheses were used to investigate by scanning electron microscopy the biofilm developing on the implant. Two main types of microbial colonization forms could be distinguished. Firstly, macroscopically visible, single colonies dominating on the esophagus side of the prosthesis were found, which were built up of mainly yeast cells. Secondly, thin microbial films on the areas in between were seen in which bacteria were the dominating organisms. In both colonization forms, mixed biofilms of mainly cocci and yeasts could also be found

Sequential release of cytokines, lipid mediators and nitric oxide in experimental colitis

The object of this study was to establish whether different pro- and anti-inflammatory mediators were formed in colonic tissue from experimental colitis depending on the course of the disease. Concentrations of mediators of inflammation were examined in colonic tissue in dextran induced colitis in mice. Initial inflammation was produced by 5 days treatment of 10% dextran sodium sulfate (DSS) in drinking water, followed by a further 9 day period of 2% DSS in an attempt to produce a milder chronic inflammation. The degree of inflammation was scored by a standardized macroscopic and histological examination. Initially, a 60% maximum inflammation score was observed at day 4. At this time inflammation was associated with the release of interleukin-lβ (IL-1β) and tumour necrosis factor-α (TNFα), whereas both prostaglandins 6kPGF1α and PGE2 and nitric oxide (NO) markedly decreased. Then a 25% inflammation score was reached which coincided with an increased production of platelet-activating factor (PAF). No significant changes were observed in leukotriene B4 and C4 formation. In conclusion, pro-inflammatory cytokines IL-1β and TNFα are considered to be primary mediators, whereas PAF, eicosanoids and NO may reflect secondary mediators in experimental colitis

Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF1α), thromboxane A2 (TxB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF1α, reflecting the pulmonary vasodilator prostacyclin (PGI2), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF1α in CDH may reflect a compensation mechanism for increased vascular resistance

Techno-economic assessment of SEWGS technology when applied to integrated steel-plant for CO2 emission mitigation

Mitigation of CO2 emissions in the industrial sector is one of the main climate challenges for the coming decades. This work, carried out within the STEPWISE H2020 project, performs a preliminary techno-economic assessment of the Sorption Enhanced Water Gas Shift (SEWGS) technology when integrated into the iron and steel plant to mitigate CO2 emissions. The SEWGS separates the CO2 from the iron and steel off-gases with residual energy content (i.e. Blast Furnace Gas, Basic Oxygen Furnace Gas and Coke Oven Gas) and the produced H2 is sent to the power generation section to produce the electricity required by the steel plant, while the CO2 is compressed and transported for storage. Detailed mass and energy balances are performed together with a SEWGS cost estimation to assess the energy penalty and additional costs related to CO2 capture. Results demonstrates the potential of SEWGS to capture over 80 % of CO2 in the off-gases, which results in entire plant CO2 emission reduction of 40 % with a Specific Energy Consumptions for CO2 Avoided (SPECCA) around 1.9 MJ/kgCO2. SEWGS outperforms a commercial amine scrubbing technology which has a SPECCA of 2.5 MJ/kgCO2 and only 20 % of CO2 avoided. The cost of CO2 avoided calculated on the basis of a fully integrated steel plant is around 33 €/tCO2 compared to 38 €/tCO2 of the amine technology

Hypomagnesemia in persons with type 1 diabetes:associations with clinical parameters and oxidative stress

Background: Among persons with type 1 diabetes mellitus (T1DM) low concentrations of magnesium have been reported. Previous (small) studies also suggested a relation of hypomagnesemia with (poor) glycaemic control and complications. We aimed to investigate the magnitude of hypomagnesemia and the associations between magnesium with parameters of routine T1DM care in a population of unselected outpatients. Methods: As part of a prospective cohort study, initially designed to measure quality of life and oxidative stress, data from 207 patients with a mean age of 45 [standard deviation (SD) 12] years, 58% male, diabetes duration 22 [interquartile range (IQR) 16, 31] years and glycated haemoglobin (HbA1c) of 60 (SD 11) mmol/mol [7.6 (SD 1.0)%] were examined. Hypomagnesemia was defined as a concentration below Results: Mean magnesium concentration was 0.78 (SD 0.05) mmol/l. A deficiency was present in 4.3% of participants. Among these persons, mean concentration was 0.66 (SD 0.03) mmol/l. There was no correlation between magnesium and HbA1c at baseline (r = -0.014, p = 0.843). In multivariable analysis, free thiols (reflecting the degree of oxidative stress) were significantly and negatively associated with magnesium concentrations. Conclusion: In this cohort of T1DM outpatients, the presence of hypomagnesemia was infrequent and, if present, relative mild. Magnesium was not associated with glycaemic control nor with presence of micro- and macrovascular complications. Although these results need confirmation, in particular the negative association of magnesium with free thiols, this suggests that hypomagnesemia is not a relevant topic in routine care for people with T1DM

Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis.

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity

HIV-Infected Children in Rural Zambia Achieve Good Immunologic and Virologic Outcomes Two Years After Initiating Antiretroviral Therapy

Background: Many HIV-infected children in sub-Saharan Africa reside in rural areas, yet most research on treatment outcomes has been conducted in urban centers. Rural clinics and residents may face unique barriers to care and treatment. Methods: A prospective cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha, Zambia. HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy (ART) during the study were eligible. Treatment outcomes during the first two years of ART, including mortality, immunologic status, and virologic suppression, were assessed and risk factors for mortality and virologic suppression were evaluated. Results: A total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment. The cumulative probabilities of death among children starting ART after study enrollment were 9.0% and 14.4% at 6 and 24 months after ART initiation. Younger age, higher viral load, lower CD4+ T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality. The mean CD4+ T-cell percentage increased from 16.3% at treatment initiation to 29.3% and 35.0% at 6 and 24 months. The proportion of children with undetectable viral load increased to 88.5% and 77.8% at 6 and 24 months. Children with longer travel times (≥5 hours) and those taking nevirapine at ART initiation, as well as children who were non-adherent, were less likely to achieve virologic suppression after 6 months of ART. Conclusions: HIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements. Children with longer travel times were less likely to achieve virologic suppression, supporting the need for decentralized models of ART delivery