Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2022
Endometriosis in an estrogen-dependent disease that is characterized by the presence of endometrial tissue outside the uterine cavity leading to pain and infertility in many affected women. Highly efficient treatment options which create a hypo-estrogenic environment can cause side effects such as hot flushes and bone mass loss that are not favorable for premenopausal women. Previous work has demonstrated that increased local or systemic prolactin seems to be involved in the pathogenesis of endometriosis.
View Article and Find Full Text PDFMaterials And Methods: Male white New Zealand rabbits (2.4-3.1 kg) in 2 study groups (n = 21 each) received 3 injections of either gadobutrol or gadoteridol at 0.
View Article and Find Full Text PDFIntroduction: Discrepancies in the measurement of modified factor VIII (FVIII) products have been recognized, highlighting the need for adjustments in clinical laboratory practices to ensure effective monitoring of patients treated with these products, particularly using the one-stage (activated partial thromboplastin time [aPTT]) assay.
Aim: To assess the ability of clinical laboratories to measure the activity of BAY 94-9027, a PEGylated extended half-life FVIII product, using routine (predominantly one-stage) assays in clinical laboratories METHODS: Blinded samples of FVIII-deficient plasma spiked with defined levels of BAY 94-9027 and a recombinant FVIII product comparator were provided to 52 clinical laboratories that routinely conduct FVIII testing. Samples were provided at 3 concentrations (low, medium and high), and laboratories analysed the samples using routine in-house one-stage and, when available, chromogenic assays.
Purpose: This article seeks to take the next step in examining the insights that nurses and other healthcare providers can derive from applying behavioral economic concepts to support genomic decision making. As genomic science continues to permeate clinical practice, nurses must continue to adapt practice to meet new challenges. Decisions associated with genomics are often not simple and dichotomous in nature.
View Article and Find Full Text PDFAberrant methylation of promoter regions involved in silencing of tumor suppressor genes is a key feature of many human cancers including melanoma. These DNA methylation events occur early in cancer development, increase with progression, and may therefore serve as biomarkers for the detection and staging of cancer. In our study, we used an epigenomic reactivation screening approach including Combined Bisulfite Restriction Analyses (COBRA) assays to identify novel methylation markers in late-stage melanoma.
View Article and Find Full Text PDFObjectives: Bisphosphonate-associated osteonecrosis of the jaws is a serious side effect that mainly occurs in patients receiving highly potent, nitrogen-containing bisphosphonates. Usually the diagnosis is made due to exposed bone and a nonhealing wound. Neutrophil granulocytes are essential for sufficient wound healing; therefore, the influence of different bisphosphonates on neutrophil granulocytes was the focus of this study.
View Article and Find Full Text PDFBackground: Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH.
Methods: We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH.
This paper presents a novel application of direct force control to test biological specimens using a serial manipulator with 6 degrees of freedom Direct force control compares actual force/moment values with desired values of load. The error is compensated by a proportional/integral controller (PI), a damping factor implemented with the velocity of the robot and acting in the direction of the force and a feedforward compensation. The controller works with a frequency of 0.
View Article and Find Full Text PDFThe incommensurate stripelike magnetic ordering in two single-layered manganites, Nd0.33Sr1.67MnO4 and Pr0.
View Article and Find Full Text PDFEndometriosis is a chronic, estrogen-dependent disease characterized by the presence of ectopic endometrium either in the pelvic cavity (endometriosis externa) or within the uterus (endometriosis interna, adenomyosis). Key symptoms are pelvic pain, dysmenorrhea and infertility. Established rodent animal models used for drug research in endometriosis have certain limitations.
View Article and Find Full Text PDFOverdoped La0.42Sr1.58MnO4 exhibits a complex ordering of charges, orbitals, and spins.
View Article and Find Full Text PDFIn this paper we present the humanoid robot LOLA, its mechatronic hardware design, simulation and real-time walking control. The goal of the LOLA-project is to build a machine capable of stable, autonomous, fast and human-like walking. LOLA is characterized by a redundant kinematic configuration with 7-DoF legs, an extremely lightweight design, joint actuators with brushless motors and an electronics architecture using decentralized joint control.
View Article and Find Full Text PDFThe prototype of a gaze-controlled, head-mounted camera (EyeSeeCam) was developed that provides the functionality for fundamental studies on human gaze behavior even under dynamic conditions like locomotion. EyeSeeCam incorporates active visual exploration by saccades with image stabilization during head, object, and surround motion just as occurs in human ocular motor control. This prototype is a first attempt to combine free user mobility with image stabilization and unrestricted exploration of the visual surround in a man-made technical vision system.
View Article and Find Full Text PDFThree series of non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting the cyclooxygenase/5-lipoxygenase (COX/5-LOX) pathways as such as formation of hydroxyl radicals and adhesion were prepared: 4,5-diaryl isothiazoles, 4,5-diaryl 3H-1,2-dithiole-3-thiones and 4,5-diaryl 3H-1,2-dithiole-3-ones. The aim of the present study was to develop substances which can intervene into the inflammatory processes via different mechanisms of action as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) with increased anti-inflammatory potential. The current lead 11a was evaluated in COX-1/2, 5-LOX and (*)OH scavenging in vitro assays and in a static adhesion assay where it proved to inhibit adhesion.
View Article and Find Full Text PDFBeagle dogs continue to be used in experimental studies and preclinical and clinical trials, many of which address the usage of anaesthesia. In order to reduce the number of animals, researchers tend to conduct several experiments on a single animal. The question arises, however, as to whether or not this frequent usage involves more than simply additional stress and discomfort for the individual animal.
View Article and Find Full Text PDFThe aim was to study the COX-1 inhibiting efficacy in context with hydroxyl radical scavenging properties of compounds bearing a carboxylic acid and ester function, respectively. In general, the acids are more potent radical scavengers than the corresponding esters but there is no clear correlation with their COX-1 inhibiting potencies. A feasible scavenging mechanism of carboxylic acids is discussed.
View Article and Find Full Text PDFGlaucoma is characterized by a loss of retinal ganglion cells (RGC) which is associated with a decrease of visual function. Neuroprotective agents as a new therapeutic strategy could prevent the remaining neurons from apoptotic cell death. Previous studies have shown the involvement of the Cyclooxygenase (COX)-2 signalling in the apoptotic death of neurons.
View Article and Find Full Text PDFThe aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.
View Article and Find Full Text PDFAn early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization.
View Article and Find Full Text PDFAngiotensin-converting enzyme (ACE) inhibitors interfere with several key events of vascular inflammation resulting in impressive reductions in coronary vascular events. However, in human arteries ACE inhibitors block the production of angiotensin II (AngII) incompletely because of the involvement of alternative pathways in local AngII formation. Therefore, our study concentrated on the presumed modulation by ACE inhibition of local AngII-mediated inflammatory actions by a mechanism independent of blockage of AngII formation.
View Article and Find Full Text PDFThe main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of mechanisms other than the reduction of inflammatory prostaglandins and leukotrienes to the anti-inflammatory effect of the LOX/COX inhibitor licofelone.
View Article and Find Full Text PDFIn acute inflammation, infiltration of neutrophils often precedes a second phase of monocyte invasion, and data in the literature suggest that neutrophils may directly stimulate mobilization of monocytes via neutrophil granule proteins. In this study, we present a role for neutrophil-derived heparin-binding protein (HBP) in monocyte arrest on endothelium. Adhesion of neutrophils to bovine aorta endothelial cells (ECs) or HUVEC-triggered secretion of HBP and binding of the protein to the EC surface.
View Article and Find Full Text PDFWe report on a facile and rapid computerized in-vitro assay for the quantification of leukocyte adhesion to endothelial cells under static conditions using bovine polymorphonuclear neutrophils (PMN) or human leukaemic Mono Mac 6 cells (MM6) and bovine aorta endothelial cells (BAEC). Images of leukocytes adherent to BAEC monolayers grown in microtiter plates were obtained by a digital camera attached to a conventional microscope and transferred to the public domain NIH ImageJ program for analysis. Using individually adapted program routines adherent leukocytes are easily discriminated and reproducibly quantified.
View Article and Find Full Text PDFBackground: Antiestrogens of the selective estrogen receptor modulator (SERM) type, such as tamoxifen, have two major limitations: their mixed agonist and antagonist profile and the development of tumor resistance. We characterized two new pure antiestrogens-ZK-703 and ZK-253-that belong to the class of specific estrogen receptor destabilizers (SERDs), which includes fulvestrant, and compared their activity with that of fulvestrant and tamoxifen.
Methods: Effects of antiestrogens on the growth of estrogen-dependent breast tumors in vivo were determined using several mouse xenograft models (including the tamoxifen-sensitive tumors MCF7, T47D, and MV3366 and the tamoxifen-resistant tumors ZR75-1 and MCF7/TAM) and chemically induced (nitrosomethyl urea [NMU] and dimethylbenzanthracene [DMBA]) rat breast cancer models (groups of 10 animals).