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Pearl Therapeutics

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https://www.readbyqxmd.com/read/27864823/aberrant-mtor-signaling-and-disrupted-autophagy-the-missing-link-in-potential-vigabatrin-associated-ocular-toxicity
#1
K R Vogel, G R Ainslie, P L Pearl, K M Gibson
Vigabatrin (VGB; γ-vinylGABA) is a unique antiepileptic directly elevating CNS GABA via inactivation of the GABA metabolic enzyme GABA-transaminase. VGB is effective in treating infantile spasms, a rare seizure disorder associated with significant morbidity. The potential for unexplained bilateral constriction of the visual field associated with VGB intervention can severely limit its temporal utility. Removal of this potential adverse effect with adjuvant intervention(s) would represent a significant advance in epilepsy therapeutics...
November 19, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27810436/different-optimal-alignment-but-equivalent-functional-outcomes-in-medial-and-lateral-unicompartmental-knee-arthroplasty
#2
Jelle P van der List, Harshvardhan Chawla, Jordan C Villa, Andrew D Pearle
INTRODUCTION: Several differences in kinematics, functional outcomes and alignment exist between medial and lateral unicompartmental knee arthroplasty (UKA). Therefore, the purpose of this study was (1) to compare functional outcomes between both procedures with the hypothesis that both have equivalent outcomes and (2) to assess the role of preoperative and postoperative alignment on functional outcomes in both procedures. METHODS: Patients who underwent UKA were included when overall function - using Western Ontario and McMaster Universities Arthritis (WOMAC) score - and joint awareness - using Forgotten Joint Score (FJS) - were available preoperatively and at minimum two-year follow-up...
October 31, 2016: Knee
https://www.readbyqxmd.com/read/27796434/novel-encapsulation-improves-recovery-of-probiotic-strains-in-fecal-samples-of-human-volunteers
#3
Volker Mai, Sheldon Waugh, Doratha Byrd, Damion Simpson, Maria Ukhanova
Probiotic supplements can contribute to maintaining health and ameliorating various disease symptoms. Probiotics can be delivered in many forms with crucial differences in their survival during gastrointestinal (GI) passage. Previously, a novel encapsulation, Probiotic Pearls™ Acidophilus, Integrative Therapeutics, LLC, USA (Pearls), was shown to increase survival in vitro after exposure to gastric conditions. Here, we compare fecal recovery in human volunteers consuming Pearls or a conventional hard-shelled gelatin capsule...
October 28, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27718775/breaking-the-cycle-of-hair-breakage-pearls-for-the-management-of-acquired-trichorrhexis-nodosa
#4
Alessandra Haskin, Shawn G Kwatra, Crystal Aguh
Acquired trichorrhexis nodosa is a common cause of hair loss for patients of all ethnicities. It is especially prevalent in black patients with tightly curled hair types and can present unique diagnostic and therapeutic challenges due to structural differences in these hair types and the combination of various hair care and styling practices that contribute to hair damage. While scalp biopsies can help rule out other etiologies of hair loss, there is a paucity of histologic findings in acquired trichorrhexis nodosa, making this primarily a clinical diagnosis...
October 10, 2016: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/27660707/into-the-clinic-talimogene-laherparepvec-t-vec-a-first-in-class-intratumoral-oncolytic-viral-therapy
#5
Hasan Rehman, Ann W Silk, Michael P Kane, Howard L Kaufman
With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27650731/transfer-of-microrna-486-5p-from-human-endothelial-colony-forming-cell-derived-exosomes-reduces-ischemic-kidney-injury
#6
Jose L Viñas, Dylan Burger, Joseph Zimpelmann, Randa Haneef, William Knoll, Pearl Campbell, Alex Gutsol, Anthony Carter, David S Allan, Kevin D Burns
Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Akt phosphorylation...
December 2016: Kidney International
https://www.readbyqxmd.com/read/27576611/antiangiogenic-antibody-improves-melanoma-detection-by-fluorescently-labeled-therapeutic-antibodies
#7
Larissa Sweeny, Andrew Prince, Neel Patel, Lindsay S Moore, Eben L Rosenthal, Brian B Hughley, Jason M Warram
OBJECTIVE: Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody-based imaging. STUDY DESIGN: Preclinical. METHODS: Panitumumab and control IgG were covalently linked to a near-infrared fluorescent probe (IRDye800CW). Immunodeficient mice with ear xenografts of melanoma cell lines (A375 and SKMEL5) were systemically injected (200 μg, tail vein) with either IgG-IRDye800CW, panitumumab-IRDye800CW, or a combination (bevacizumab [5mg/kg], administered 72 hours prepanitumumab-IRDye800CW) (n = 5)...
August 31, 2016: Laryngoscope
https://www.readbyqxmd.com/read/27516097/spontaneous-dissections-of-the-anterior-cerebral-artery-a-meta-analysis-of-the-literature-and-three-recent-cases
#8
Johannes Hensler, Ulf Jensen-Kondering, Stephan Ulmer, Olav Jansen
INTRODUCTION: Spontaneous dissections of intracranial arteries are rare, but important causes of stroke, especially in younger patients. Dissections of the anterior cerebral artery (ACA) have been reported only very rarely in the European and North American populations but might be more prevalent than previously thought. METHODS: This paper describes the presenting pattern of the disease, the clinical and imaging findings, as well as endovascular therapeutical options with respect to a meta-analysis of cases reported in the literature...
August 11, 2016: Neuroradiology
https://www.readbyqxmd.com/read/27465158/lumbar-artery-perforator-flap-an-anatomical-study-using-multidetector-computed-tomographic-scan-and-surgical-pearls-for-breast-reconstruction
#9
Moustapha Hamdi, Barbara Craggs, Carola Brussaard, Katrin Seidenstueker, Benoit Hendrickx, Assaf Zeltzer
BACKGROUND: Breast reconstruction with the lumbar artery perforator flap is indicated in patients with unfavorable abdominal donor site. In addition to their clinical experience with lumbar artery perforator free flap breast reconstruction, the authors present an anatomical study of the origin and course of the perforators. METHODS: Images of multidetector computerized tomography scans were used to visualize the location of the dominant lumbar artery perforator in 20 patients...
August 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27398883/imaging-the-dna-alkylator-melphalan-by-cest-mri-an-advanced-approach-to-theranostics
#10
Ethel J Ngen, Amnon Bar-Shir, Anna Jablonska, Guanshu Liu, Xiaolei Song, Roxana Ansari, Jeff W M Bulte, Miroslaw Janowski, Monica Pearl, Piotr Walczak, Assaf A Gilad
Brain tumors are among the most lethal types of tumors. Therapeutic response variability and failure in patients have been attributed to several factors, including inadequate drug delivery to tumors due to the blood-brain barrier (BBB). Consequently, drug delivery strategies are being developed for the local and targeted delivery of drugs to brain tumors. These drug delivery strategies could benefit from new approaches to monitor the delivery of drugs to tumors. Here, we evaluated the feasibility of imaging 4-[bis(2-chloroethyl)amino]-l-phenylalanine (melphalan), a clinically used DNA alkylating agent, using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI), for theranostic applications...
September 6, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27394707/cabergoline-treatment-for-recurrent-cushing-s-disease-during-pregnancy
#11
Afif Nakhleh, Leonard Saiegh, Maria Reut, Mohammad Sheikh Ahmad, Irit Wirsansky Pearl, Carmela Shechner
OBJECTIVE: Cushing's disease during pregnancy is associated with an increased risk for maternal and fetal complications. In recurrent Cushing`s disease following transsphenoidal surgery, and when re-operation is not feasible, medical treatment is usually considered. Cabergoline was found to be effective in reducing hypercortisolism in Cushing's disease. Evolving data concerning the safety of cabergoline use during pregnancy show no significant increase in the rate of complications during pregnancy or the postnatal period...
July 2016: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27284061/mutational-patterns-in-oncogenes-and-tumour-suppressors
#12
REVIEW
Hanadi M Baeissa, Graeme Benstead-Hume, Christopher J Richardson, Frances M G Pearl
All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved...
June 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27188913/transthyretin-cardiac-amyloidosis-in-black-americans
#13
Keyur B Shah, Anit K Mankad, Adam Castano, Olakunle O Akinboboye, Phillip B Duncan, Icilma V Fergus, Mathew S Maurer
Transthyretin-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive and hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts black Americans, who when compared with whites with wild-type transthyretin amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a noninvasive method for early identification (genetic testing). Although reasons for this are unclear, this begs to consider the inadequate access to care, societal factors, or a biological basis...
June 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/27099339/mode-of-action-of-dna-competitive-small-molecule-inhibitors-of-tyrosyl-dna-phosphodiesterase-2
#14
Peter Hornyak, Trevor Askwith, Sarah Walker, Emilia Komulainen, Michael Paradowski, Lewis E Pennicott, Edward J Bartlett, Nigel C Brissett, Ali Raoof, Mandy Watson, Allan M Jordan, Donald J Ogilvie, Simon E Ward, John R Atack, Laurence H Pearl, Keith W Caldecott, Antony W Oliver
Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a 5'-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II (TOP2). TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain...
July 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27095959/long-term-intermittent-pharmacological-therapy-of-uterine-fibroids-a-possibility-to-avoid-hysterectomy-and-its-negative-consequences
#15
REVIEW
Anita Olejek, Katarzyna Olszak-Wąsik, Anna Czerwinska-Bednarska
Uterine fibroids are found in almost 20-40% of women of reproductive age. For each woman an individualised treatment method should be applied because the hysterectomy procedure is not a good option in every case. The uterus is an organ necessary not only in reproduction. Its removal may result in: pelvic floor dysfunction and stress urinary incontinence, negative impair on life quality, depressive disorders, increased risk of cardiovascular and neurodegenerative diseases, and higher incidence of neoplastic disease...
March 2016: Przeglad Menopauzalny, Menopause Review
https://www.readbyqxmd.com/read/27071333/biocompatibility-of-ferritin-based-nanoparticles-as-targeted-mri-contrast-agents
#16
Jennifer R Charlton, Valeria M Pearl, Anna R Denotti, Jonathan B Lee, Sundararaman Swaminathan, Yogesh M Scindia, Nathan P Charlton, Edwin J Baldelomar, Scott C Beeman, Kevin M Bennett
Ferritin is a naturally occurring iron storage protein, proposed as a clinically relevant nanoparticle with applications as a diagnostic and therapeutic agent. Cationic ferritin is a targeted, injectable contrast agent to measure kidney microstructure with MRI. Here, the toxicity of horse spleen ferritin is assessed as a step to clinical translation. Adult male mice received cationic, native and high dose cationic ferritin (CF, NF, or HDCF) or saline and were monitored for 3weeks. Transient weight loss occurred in the ferritin groups with no difference in renal function parameters...
August 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27048228/bortezomib-may-stabilize-pediatric-renal-transplant-recipients-with-antibody-mediated-rejection
#17
Meghan H Pearl, Anjali B Nayak, Robert B Ettenger, Dechu Puliyanda, Miguel Fernando Palma Diaz, Qiuheng Zhang, Elaine F Reed, Eileen W Tsai
BACKGROUND: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients. METHODS: We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite...
August 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/26998310/parental-attitudes-to-genetic-testing-differ-by-ethnicity-and-immigration-in-childhood-nephrotic-syndrome-a-cross-sectional-study
#18
Karlota Borges, Jovanka Vasilevska-Ristovska, Neesha Hussain-Shamsy, Viral Patel, Tonny Banh, Diane Hebert, Rachel J Pearl, Seetha Radhakrishnan, Tino D Piscione, Christoph P B Licht, Valerie Langlois, Leo Levin, Lisa Strug, Rulan S Parekh
BACKGROUND: Studies in the USA report differences in opinion among parents of different ethnic groups toward genetic testing for their child; however, there are no studies that address this issue in the diverse ethnic and immigrant population in Canada. OBJECTIVE: This study aims to determine whether ethnicity and immigration status influences parental interest in clinical genetic testing for a potentially progressive kidney disease. DESIGN: This is a cross-sectional study...
2016: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/26995012/assessment-of-vitamin-d-status-and-response-to-vitamin-d3-in-obese-and-non-obese-iranian-children
#19
Yasaman Motlaghzadeh, Fatemeh Sayarifard, Bahar Allahverdi, Ali Rabbani, Aria Setoodeh, Azadeh Sayarifard, Farzaneh Abbasi, Mohammad-Taghi Haghi-Ashtiani, Abbas Rahimi-Froushani
BACKGROUND: Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. METHODS: In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2-14 years was measured...
August 2016: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/26991466/review-the-hsp90-molecular-chaperone-an-enigmatic-atpase
#20
REVIEW
Laurence H Pearl
The HSP90 molecular chaperone is involved in the activation and cellular stabilization of a range of 'client' proteins, of which oncogenic protein kinases and nuclear steroid hormone receptors are of particular biomedical significance. Work over the last two decades has revealed a conformational cycle critical to the biological function of HSP90, coupled to an inherent ATPase activity that is regulated and manipulated by many of the co-chaperones proteins with which it collaborates. Pharmacological inhibition of HSP90 ATPase activity results in degradation of client proteins in vivo, and is a promising target for development of new cancer therapeutics...
August 2016: Biopolymers
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