Non-steroidal anti-inflammatory drug (NSAID)-induced colonic strictures and perforation: A case report

Although non-steroidal anti-inflammatory drug-induced colopathy is well described, colonic perforations complicating non-steroidal anti-inflammatory drug intake are rare. We report a patient with rheumatoid arthritis who was on long-term diclofenac and presented with early colonic stricture formation and a caecal perforation, which to the best of our knowledge, has only been reported once before. It is important to suspect this diagnosis in patients on non-steroidal anti-inflammatory drug therapy who present with an acute abdomen.     

Modified FMCW system for non-contact sensing of human respiration

Abstract

Small displacement detection capability becomes an important key for developing non-contact sensor for human respiration based on radar system. Frequency modulated continuous wave (FMCW) radar has been widely studied and applied for many applications. With respect to the conventional perspective, large bandwidth is needed for detecting the small displacement related to the human respiration. Meanwhile, extracting the respiration pattern from Doppler response has a drawback in identifying the small displacement location. In this paper, the modification on FMCW system was proposed for obtaining the capability in detecting the human respiration and its distance from the radar. Detecting the phase value of the low pass filter (LPF), output from conventional FMCW was investigated and applied as a modification concept. The pattern, rate and amplitude of respiration are extracted from phase detector output. Beat frequency detection is still elaborated for synthesising the reference signal for phase detection. The result shows that the modified FMCW system proposed the capability of detecting the rate and amplitude respiration and location of the target.     

A meta-summary of case reports of non-vitamin K antagonist oral anticoagulant use in patients with left ventricular thrombus

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR?=?22.5–47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.     

Pleurotus ostreatus,an edible mushroom,enhances glucose 6-phosphate dehydrogenase,ascorbate peroxidase and reduces xanthine dehydrogenase in major organs of aged rats

Context: Aging is now considered to be associated with an elevation in oxidative damage to macromolecules and enhanced levels of inflammation. Therefore, inhibition of age-related oxidative stress by natural supplement is an important study.

Objectives: To investigate whether the treatment with Pleurotus ostreatus (Jacq.: Fr) Kumm, (Pleurotaceae) can ameliorate oxidative damage in aged rats.

Materials and methods: Male Wistar rats were divided into three groups of six each: group 1, normal young rats; group 2, normal aged untreated rats; group 3, normal aged rats treated with P. ostreatus (200?mg/kg body wt administered intraperitoneally for 21 days). On the 22nd day, rats were sacrificed by decapitation; the liver, kidneys, heart and brain were removed from each rat for the biochemical and isozyme analyses of the antioxidant enzymes glucose 6-phosphate dehydrogenase (G6PDH), ascorbate peroxidase (Apx) and xanthine dehydrogenase (XDH).

Results: An elevated activity of XDH was observed in the liver (G2:13.72?±?4.1 versus G1: 7.57?±?1.15; p?p?p?p?P. ostreatus to aged rats resulted in decreased XDH and increased G6PDH and Apx activities in liver, kidneys, heart and brain. Interestingly, analyses of isozyme pattern of these enzymes are support the results obtained from the spectrophotometric determinations.

Conclusion: These results suggest that an extract of P. ostreatus can protect the age-related oxidative damage in major organs of Wistar rats by enhancing the antioxidant enzymes G6PDH and Apx and by reducing XDH.     

Improving the Specificity of the Prostate‐Specific Antigen Substrate Glutaryl‐Hyp‐Ala‐Ser‐Chg‐Gln as a Promoiety

To develop PSA peptide substrates with improved specificity and plasma stability from the known substrate sequence glutaryl‐Hyp‐Ala‐Ser‐Chg‐Gln, systematic replacements of the N‐terminal segment with D‐retro‐inverso‐peptides were performed with the incorporation of 7‐amino‐4‐methylcoumarin (7‐AMC) after Gln for convenient fluorometric determination and ranking of the PSA substrate activity. The D‐retro‐inverso‐peptide conjugates with P2‐P5 D‐amino acid substitutions were moderate but poorer PSA substrates as compared to the original peptide, suggesting that inversion of the amide bonds and/or incorporation of the additional atom as in the urea linker adversely affected PSA binding. However, P5 substitution of Hyp with Ser showed significant improvements in PSA cleavage rate; the resulting AMC conjugate, glutaryl‐Ser‐Ala‐Ser‐Chg‐Gln‐AMC ( 11 ), exhibited the fastest PSA cleavage rate of 351 pmol/min/100 nmol PSA. In addition, GABA←mGly‐Ala‐Ser‐Chg‐Gln‐AMC (conjugate 6 ) was the second best PSA substrate and released 7‐AMC at a rate of 225 pmol/min/100 nmol PSA as compared to 171 pmol/min/100 nmol PSA for the control conjugate glutaryl‐Hyp‐Ala‐Ser‐Chg‐Gln‐AMC. Incubations of selected AMC conjugates with mouse and human plasma revealed that GABA←D‐Ser‐ψ[NH‐CO‐NH]‐Ala‐Ser‐Chg‐Gln‐AMC ( 5 ) and GABA←mGly‐Ala‐Ser‐Chg‐Gln‐AMC ( 6 ) were most stable to non‐PSA‐mediated proteolysis. Our results suggest that the PSA specificity of glutaryl‐Hyp‐Ala‐Ser‐Chg‐Gln is improved with Ser and mGly substitutions of Hyp at the P5.     

Trypanosomatidae produce acetate via a mitochondrial acetate:succinate CoA transferase

Hydrogenosome-containing anaerobic protists, such as the trichomonads, produce large amounts of acetate by an acetate:succinate CoA transferase (ASCT)/succinyl CoA synthetase cycle. The notion that mitochondria and hydrogenosomes may have originated from the same α-proteobacterial endosymbiont has led us to look for the presence of a similar metabolic pathway in trypanosomatids because these are the earliest-branching mitochondriate eukaryotes and because they also are known to produce acetate. The mechanism of acetate production in these organisms, however, has remained unknown. Four different members of the trypanosomatid family: promastigotes of Leishmania mexicana mexicana, L. infantum and Phytomonas sp., and procyclics of Trypanosoma brucei were analyzed as well as the parasitic helminth Fasciola hepatica. They all use a mitochondrial ASCT for the production of acetate from acetyl CoA. The succinyl CoA that is produced during acetate formation by ASCT is recycled presumably to succinate by a mitochondrial succinyl CoA synthetase, concomitantly producing ATP from ADP. The ASCT of L. mexicana mexicana promastigotes was further characterized after partial purification of the enzyme. It has a high affinity for acetyl CoA (K_m 0.26 mM) and a low affinity for succinate (K_m 6.9 mM), which shows that significant acetate production can occur only when high mitochondrial succinate concentrations prevail. This study identifies a metabolic pathway common to mitochondria and hydrogenosomes, which strongly supports a common origin for these two organelles.     

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature

Journal of Thrombosis and Thrombolysis - Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association...     

Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence,Enhanced Telomere Erosion,and Degradation of Werner’s Syndrome Protein

Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence.Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF).Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length.Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening.Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911