Publications by authors named "G Koller"

192 Publications

Selective and marked blockade of endothelial sprouting behavior using paclitaxel and related pharmacologic agents.

Am J Pathol 2021 Sep 23. Epub 2021 Sep 23.

Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida School of Medicine, Tampa, FL 33612. Electronic address:

Here, we investigate whether alterations in the microtubule cytoskeleton affect the ability of ECs to sprout and form branching networks of tubes. Using defined bioassays of human EC tubulogenesis, where both sprouting behavior and lumen formation can be rigorously evaluated, we demonstrate that addition of the microtubule stabilizing drugs, paclitaxel, docetaxel, ixabepilone, and epothilone B completely interfere with EC tip cells and sprouting behavior, while allowing for EC lumen formation. In bioassays mimicking vasculogenesis using single or aggregated ECs, these drugs induce ring-like lumens from single cells or cyst-like spherical lumens from multicellular aggregates with no evidence of EC sprouting behavior. Remarkably, treatment of these cultures with a low dose of the microtubule destabilizing drug, vinblastine, leads to an identical result with complete blockade of EC sprouting, but allowing for EC lumen formation. Supporting our findings, administration of paclitaxel in vivo markedly interferes with angiogenic sprouting behavior in developing mouse retina. These findings reveal novel biological activities for pharmacologic agents that are widely utilized in multidrug chemotherapeutic regimens for the treatment of human malignant cancers. Overall, this work demonstrates that manipulation of microtubule stability selectively interferes with the ability of ECs to sprout, a necessary step to initiate and form branched capillary tube networks.
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http://dx.doi.org/10.1016/j.ajpath.2021.08.017DOI Listing
September 2021

The impact of an enhanced infection control protocol on molar root canal treatment outcome - a randomized clinical trial.

Int Endod J 2021 Aug 5. Epub 2021 Aug 5.

Department of Endodontics, Centre for Oral, Clinical and Translational Sciences, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK.

Aim: To evaluate the effect of an enhanced infection control protocol on root canal treatment outcomes and on microbial load within root canals after chemomechanical preparation.

Methodology: A total of 144 molar teeth from 139 healthy patients receiving primary root canal treatment were block randomized to a standard protocol (StP) or an enhanced infection control protocol (EnP). Both treatment arms adhered to current best practice recommendations, while the EnP comprised additional steps that included replacing rubber dams, gloves, files, all instruments and surface barriers at the time of canal filling to reduce the chances of iatrogenic contamination. Patients and radiographic examiners were blinded to the protocol used. Intracanal microbial samples were taken at baseline (S1) and after completion of chemomechanical preparation (S2). Microbial 16S rDNA copy numbers were enumerated by quantitative polymerase chain reaction (qPCR). Cone beam computed tomography (CBCT) scans were taken before treatment and at one-year follow-up. The outcome was assessed clinically and radiographically using CBCT by logistic regression modelling.

Results: At one-year follow-up, 115 teeth were analysed (54 in StP and 61 in EnP). The percentage of favourable outcomes assessed by CBCT was 85.2% in the EnP and 66.7% in the StP. The odds of 12-month success was three times higher in the EnP group compared with the StP group (OR=2.89; p=0.022, CI: 1.17 - 7.15). The median bacterial reads were reduced from 8.1×10 in S1 samples to 3.5×10 in the StP group and from 8.6×10 to 1.3×10 in the EnP group. The enhanced protocol significantly reduced bacterial counts in pre-canal filling samples when compared to the standard protocol (p=0.009).

Conclusions: The implementation of a facile, enhanced infection control protocol in primary root canal treatment resulted in less detectable bacterial DNA before canal filling and significantly more successful outcomes at one year.
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http://dx.doi.org/10.1111/iej.13605DOI Listing
August 2021

Evaluation of care delivery by a novel multidisciplinary bone health clinic for patients at risk of glucocorticoid-induced osteoporosis.

Arch Osteoporos 2021 07 7;16(1):108. Epub 2021 Jul 7.

Department of Medicine, Division of Rheumatology, University of Alberta, 8-130 Clinical Sciences Building, 11350 83rd Avenue NW, Edmonton, AB, T6G 2G3, Canada.

Glucocorticoid-induced osteoporosis (GIOP) is a common condition associated with increased risk for fracture. Many patients receive suboptimal care. We created a novel GIOP clinic model which successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population.

Introduction: This study characterizes the patient population referred to our novel glucocorticoid-induced osteoporosis (GIOP) clinic and evaluates how well the clinic performed in addressing key components of GIOP preventive care.

Methods: This population-based prospective cohort study derives data from patients reviewed at the University of Alberta Multidisciplinary Bone Health Clinic from January 2017 to September 2019. To create our clinic model, key components of GIOP preventive care were summarized based on current guidelines, and clear responsibilities were delegated to each multidisciplinary team member. A REDCap database was constructed, and each patient's multidisciplinary assessment was entered at each visit. Demographic and treatment data was extracted from our database.

Results: The clinic was able to achieve optimal GIOP preventive care in 60.1% of patients and in 78.7% of patients when excluding wait time. Of the 245 GIOP patients assessed, over half were females (56.7%) and the mean age was 56.7 years (range 16-95 years). Referrals were primarily made by specialists. Low-trauma fractures were reported in 24.9% of patients and 95.5% of patients had a baseline dual-energy X-ray absorptiometry (DXA). The mean current daily prednisone-equivalent dose was 14.1 mg. All patients received a recommendation for pharmacotherapy (100%) and the majority received counseling on vitamin D (98.8%), calcium (97.8%), smoking cessation (98.8%), alcohol reduction (98.4%), falls prevention (88.6%), and exercise (85.3%).

Conclusion: Our novel GIOP clinic model successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. Further studies are required to assess the real-world long-term outcomes of our model.
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http://dx.doi.org/10.1007/s11657-021-00979-6DOI Listing
July 2021

Bis[2-(Methacryloyloxy) Ethyl] Phosphate as a Primer for Enamel and Dentine.

J Dent Res 2021 Sep 8;100(10):1081-1089. Epub 2021 Jul 8.

Centre for Oral, Clinical and Translational Sciences, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK.

Dental resin composites are commonly used in the restorative management of teeth via adhesive bonding, which has evolved significantly over the past few decades. Although current self-etch bonding systems decrease the number of clinical steps, the acidic functional monomers employed exhibit a limited extent of demineralization of enamel in comparison to phosphoric acid etchants, and the resultant superficial ionic interactions are prone to hydrolysis. This study evaluates the etching of primers constituted with bis[2-(methacryloyloxy) ethyl] phosphate (BMEP) of dental hard tissue, interfacial characteristics, and inhibition of endogenous enzymes. We examine the incorporation of 2 concentrations of BMEP in the formulation of experimental primers used with a hydrophobic adhesive to constitute a 2-step self-etching bonding system and compare to a commercial 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing system. The interaction of the primer with enamel and dentine was characterized using scanning electron, confocal laser scanning, and Raman microscopy while the polymerization reaction between the BMEP primers and hydroxyapatite was evaluated by Fourier-transform infrared spectroscopy. The inhibitory effect against matrix metalloproteinase (MMP) enzymes of these primers was studied and percentage of inhibition analyzed using 1-way analysis of variance and Tukey's post hoc test ( < 0.05). Results of the scanning electron microscopy micrographs demonstrated potent etching of both enamel and dentine with the formation of longer resin tags with BMEP primers compared to the 10-MDP-based system. The BMEP polymerized on interaction with pure hydroxyapatite in the dark, while the 10-MDP primer exhibited the formation of salts. Furthermore, BMEP primers were able to inhibit MMP activity in a dose-dependent manner. BMEP could be used as a self-etching primer on enamel and dentine, and the high degree of polymerization in the presence of hydroxyapatite can contribute to an increased quality of the resin polymer network, prompting resistance to gelatinolytic and collagenolytic degradation.
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http://dx.doi.org/10.1177/00220345211023477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381596PMC
September 2021

Inhalant Abuse of Ethyl Chloride Spray: A Case Report.

Fortschr Neurol Psychiatr 2021 Jul 8;89(7-08):382-384. Epub 2021 Jul 8.

Psychiatrie LMU, Ludwig-Maximilians-Universität München Medizinische Fakultät, München, Germany.

Ethyl chloride spray, which is usually used to relieve pain after injuries, is increasingly being used as a sniffing alternative. The number of people using this is rising due to its easy availability, cost-effectiveness and legality. The high lipid solubility of ethyl chloride leads to a rapid absorption of it in the lungs. However, data on the biotransformation of ethyl chloride in humans are sparse. We present the case of a 53-year-old male who had been inhaling ethyl chloride up to 3 times a week since 25 years, and describe his symptoms and the circumstances of abuse. This should help raise awareness of this issue so that abuse can be recognized early and rapid action taken.
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http://dx.doi.org/10.1055/a-1483-9865DOI Listing
July 2021
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