Renal adverse effects caused by NSAID in dogs

Icke steroida antiinflammatoriska läkemedel (non steroidal anti-inflammatory drugs, NSAIDs) är en stor grupp läkemedel som har antiinflammatoriska, smärtstillande och febernedsättande effekter. Verkningsmekanism är att de hämmar enzymet cyklooxygenas (COX) vilket är det första enzym som omvandlar arakidonsyra till bland annat prostaglandiner (PG). Det finns flera isozymer av COX, varav COX-1 och COX-2 är de vanligaste målenzymen för NSAIDs. PG är involverade i flertalet viktiga processer i kroppen exempelvis smärta, feber och inflammation. NSAIDs kan grovt delas in i två grupper, traditionella icke-selektiva substanser som hämmar både COX-1 och COX-2 (oftast är substanserna mer selektiva för COX-1) samt coxiber som är selektiva för COX-2. Syftet med denna litteraturstudie är att kartlägga njurbiverkningar orsakade av NSAIDs hos hund samt om biverkningarna skiljer sig åt mellan icke-selektiva substanser och coxiber. I njuren finns COX både konstitutivt och inducerbart. Hos hund finns COX-2 konstitutivt i uppåtgående delen av Henles slynga, macula densa och de medullära interstitialcellerna. COX-1 finns konstitutivt i njurens kärlbädd och i samlingsrören. PG har flera viktiga funktioner i njuren och spelar därför en viktig roll. PG är vasodilaterande och detta är speciellt viktigt då blodflödet till njuren är nedsatt. PG kan även påverka elektrolytbalansen, ge ett cellulärt skydd av njurcellerna vid en påfrestande miljö som vid höga elektrolytkoncentrationer samt ge en frisättning av renin. Då blodflödet till njuren är nedsatt och njuren därför är beroende av prostaglandiner för att upprätthålla en tillräcklig blodtillförsel kan en behandling med NSAID orsaka ischemi och nekros av njurcellerna. Vid administrering av icke-selektiva substanser till friska hundar i rekommenderade doser verkar det endast finnas ringa njurkomplikationer. Det är även visat att hypovolemi är en predisponerande faktor för att hundar drabbas av biverkningar på njuren. Vid administrering av COX-2 selektiva NSAIDs,coxiber,till friska hundar finns motstridiga resultat avseende negativ påverkan på njuren beroende på vilken substans som studerats. De förändringar som påvisats är ökade koncentrationer av kreatinin och urea i blodet samt papillär nekros och tubulär degeneration. Vid jämförelsen mellan icke-selektiva och selektiva NSAIDs blir osäkerheten stor eftersom studierna är genomförda på olika sätt och att forskarna använt sig av olika markörer för att mäta njurfunktionen.Dessutom saknas studier av hur hypovolemiska hundar reagerar av coxiber. För närvarande saknas tillräckligt med underlag för att säkert kunna dra en slutsats av hur njurbiverkningarna hos hund skiljer sig åt mellan icke-selektiva substanser och coxiber. Dock finns det en antydan till att åtminstone vissa coxiber kan ha en sämre biverkningsprofil på njuren.Non steroidal anti-inflammatory drugs (NSAIDs) is a large heterogeneous group with anti-inflammatory, analgetic and antipyretic effects. They inhibit the enzyme cyclooxygenase (COX). COX is involved in transforming arachidonic acid to prostaglandins (PGs). There are several different isoenzymes of COX, where COX-1 and COX-2 are the most important target enzymes of NSAIDs. PGs are involved in many important reactions such as pain, fever and inflammation. NSAIDs can be divided into two groups, traditional non-selective substances which inhibit both COX-1 and COX-2 (even though they are usually more selective for COX-1) and coxibs that are selective for COX-2. The aim of this study is to evaluate the renal adverse effects caused by NSAIDs in dogs and also to compare the renal effects caused by non-selective substances and coxibs. COX is both constitutive and inducible in the kidneys. In dogs COX-2 is constitutive in the ascending loop of Henles, macula densa, and the medullary interstitial cells. COX-1 is constitutive in the renal vasculature and the collecting ducts. PGs have several important functions in the kidney. First, they contribute to vasodilatation, which is fundamental when the perfusion of the kidney is reduced. Furthermore, PGs are involved in maintaining the concentration of electrolytes, giving a cellular protection of renal cells during high concentration of electrolytes. In addition they also stimulate the release of renin hormone. When the renal blood flow is decreased, the perfusion of the kidney is highly dependent on PGs and it is possible that treatment with NSAIDs may cause renal ichemia and necrosis. When administrating recommended doses of non-selective substances to healthy dogs the risk of renal adverse effects seems to be limited. Hypovolemia has shown to be predisposing for adverse effects. When treated with coxibs, the results on how the kidneys react are dissimilar. Adverse effects of some coxibs is increased serum concentration of creatinine and urea, but also papillary necrosis and tubular degeneration. The studies of non-selective NSAIDs and coxibs were not performed in the same way and the renal function was not measured with the same parameters. There are no studies found on hypovolemic dogs treated with coxibs. At present, there is not enough evidence to make a conclusion of how the renal adverse effects differ between non-selective substances and coxibs. However, the results in this literature study suggest some coxibs may possibly have more renal adverse effect than the non-selective NSAIDs

Анализ процесса самозатачивания ножей измельчающего барабана кормоуборочного комбайна

Материалы XIII Междунар. науч.-техн. конф. студентов, магистрантов и молодых ученых, Гомель, 25–26 апр. 2013 г

Low Progesterone and Low Estradiol Levels Associate with Abdominal Aortic Aneurysms in Men

Context Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.ObjectiveTo describe the associations between serum sex steroids and early, screening-detected AAA in men.MethodsWe validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.Outcomes includedAssociations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.ResultsDehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI 1.18-2.22]) and estradiol (1.40 [95% CI 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI 2.25-7.31]).​​​​​​​ConclusionMeasured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independently of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.</p

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis