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https://www.readbyqxmd.com/read/27399164/endogenous-plasma-and-salivary-uracil-to-dihydrouracil-ratios-and-dpyd-genotyping-as-predictors-of-severe-fluoropyrimidine-toxicity-in-patients-with-gastrointestinal-malignancies
#1
Andrés Fernando Andrade Galarza, Rafael Linden, Marina Venzon Antunes, Roberta Zilles Hahn, Suziane Raymundo, Anne Caroline Cezimbra da Silva, Rodrigo Staggemeier, Fernando Rosado Spilki, Gilberto Schwartsmann
OBJECTIVE: The aim of this study was to evaluate the use of plasma and saliva uracil (U) to dihydrouracil (UH2) metabolic ratio and DPYD genotyping, as a means to identify patients with dihydropyrimidine dehydrogenase (DPD) deficiency and fluoropyrimidine toxicity. METHODS: Paired plasma and saliva samples were obtained from 60 patients with gastrointestinal cancer, before fluoropyrimidine treatment. U and UH2 concentrations were measured by LC-MS/MS. DPYD was genotyped for alleles *7, *2A, *13 and Y186C...
July 11, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27265751/lrrk2-knockdown-in-zebrafish-causes-developmental-defects-neuronal-loss-and-synuclein-aggregation
#2
Shubhangi Prabhudesai, Fatima Zahra Bensabeur, Rashed Abdullah, Indranil Basak, Solange Baez, Guido Alves, Nathalia G Holtzman, Jan Petter Larsen, Simon Geir Møller
Although mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ∼50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles...
August 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27152606/a-case-of-hypersensitivity-to-progesterone-presenting-as-an-eczematous-eruption
#3
A Tammaro, P Tuchinda, F Pigliacelli, C Halvorson, G Kao, S Persechino, A A Gaspari
Hypersensitivity to progesterone is a rare condition, and it represents a hypersensitivity reaction to endogenous progesterone. Here we report a case of a woman who presented to our attention for evaluation of a rash for a few years on her posterior elbows, forearms, and right lateral lower extremity. We report this case because it describes a rare clinical entity, with an atypical clinical presentation pemphigoid-like, that is rarely described in literature.
May 2016: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26683146/endosomal-toll-like-receptors-in-clinically-overt-and-silent-autoimmunity
#4
REVIEW
Robert M Clancy, Androo J Markham, Jill P Buyon
Toll-like receptors (TLRs), first identified as pattern recognition receptors, are now recognized to serve as a key interface between innate and adaptive immunity. Systemic lupus erythematosus (SLE) is characterized by both continuous and cyclic stimulation of the innate and adaptive immune system by endogenous nucleic acids released from apoptotic or necrotic cells. TLR7 and TLR9 function as innate sensors of viral infection as their ligands are ssRNA and dsDNA, respectively. Recognition of self nucleic acids by endosomal TLRs in B cells and pDCs is thought to be an important step in the pathogenesis of SLE, generating anti-nuclear antibodies and producing type I IFN...
January 2016: Immunological Reviews
https://www.readbyqxmd.com/read/26618820/progressively-worsening-cyclic-rash-diagnosis-and-approach-to-care
#5
Angela DeRosa, Shellee Adams, Erin Kathleen Fee
Autoimmune progesterone dermatitis (AIPD) is an uncommon condition in which allergic dermatitis to endogenous progesterone manifests in cyclic cutaneous eruptions. In this case series, we present 3 patients with AIPD, each with unique presentations and medical histories emblematic of the disease. Cyclic dermatitis related to menses in a premenopausal woman should raise high clinical suspicion for AIPD, especially in the primary care or emergency setting. Because of the rarity of this disorder, this case series seeks to describe AIPD to medical providers of young women, as well as present relevant literature related to the disease...
December 2015: Journal of the American Osteopathic Association
https://www.readbyqxmd.com/read/26440210/xenopus-borealis-as-an-alternative-source-of-oocytes-for-biophysical-and-pharmacological-studies-of-neuronal-ion-channels
#6
Ben Cristofori-Armstrong, Ming S Soh, Sahil Talwar, Darren L Brown, John D O Griffin, Zoltan Dekan, Jennifer L Stow, Glenn F King, Joseph W Lynch, Lachlan D Rash
For the past 30 years, oocytes from Xenopus laevis have been extensively used to express and characterise ion channels in an easily controlled environment. Here we report the first use of oocytes from the closely related species Xenopus borealis as an alternative expression system for neuronal ion channels. Using the two-electrode voltage-clamp technique, we show that a wide variety of voltage- and ligand-gated ion channels have the same channel properties and pharmacological profiles when expressed in either X...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26383532/ovariectomy-is-associated-with-metabolic-impairments-and-enhanced-mammary-tumor-growth-in-mkr-mice
#7
Sarit Ben-Shmuel, Eyal J Scheinman, Rola Rashed, Zila Shen Orr, Emily J Gallagher, Derek LeRoith, Ran Rostoker
Obesity and type 2 diabetes (T2D) are associated with an increased risk of breast cancer incidence and mortality. Common features of obesity and T2D are insulin resistance and hyperinsulinemia. A mammary tumor promoting effect of insulin resistance and hyperinsulinemia was demonstrated in the transgenic female MKR mouse model of pre-diabetes inoculated with mammary cancer cells. Interestingly, in MKR mice, as well as in other diabetic mouse models, males exhibit severe hyperglycemia, while females display insulin resistance and hyperinsulinemia with only a mild increase in blood glucose levels...
December 2015: Journal of Endocrinology
https://www.readbyqxmd.com/read/26175195/plerixafor-may-treat-intractable-post-herpetic-neuralgia
#8
Fang Xie, Xueyang Li, Mengmeng Bao, Ruijuan Guo, Chen Zhang, Anshi Wu, Yun Yue, Yun Guan, Yun Wang
Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia. A reactivation of latent VZV leads to herpes zoster (shingles). Herpes zoster often causes herpetic pain that can last for months or years after the rash has healed. Prolonged herpetic pain is defined as post-herpetic neuralgia (PHN). There is an unmet need to explore novel therapeutic approaches for intractable PHN. Postmortem studies have shown that VZV induces neuro-inflammation and damage to the ganglia and spinal cord...
October 2015: Medical Hypotheses
https://www.readbyqxmd.com/read/26034748/radical-improvement-of-signs-and-symptoms-in-systemic-lupus-erythematosus-when-treated-with-hemodiafiltration-with-endogenous-reinfusion-dialysis
#9
Francesco Giuseppe Solano, Elisa Bellei, Aurora Cuoghi, Marialuisa Caiazzo, Francesco Bruni
Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching...
January 2015: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/26011402/possible-role-of-proenkephalin-in-psoriasis
#10
N A Nagui, M A Ezzat, H M Abdel Raheem, L A Rashed, N A Abozaid
BACKGROUND: Psoriasis is a common chronic skin disease that can also affect the mucous membranes and joints. It is multifactorial in origin, occurring in genetically predisposed individuals, and triggered by various endogenous and exogenous factors. Proenkephalin (PENK) is an endogenous opioid polypeptide hormone that acts on specific opiate receptors found on nerve and mucosal cells, and on various cells in the immune system. PENK receptors are expressed on skin cells, and their activation can regulate keratinocyte and melanocyte activities...
March 2016: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/25873549/atypical-presentation-of-a-common-disease-shingles-of-the-larynx
#11
Sarah Hosseini, Faisal Zawawi, Jonathan Young
OBJECTIVE: Herpes zoster is a neurocutaneous disease resulting from the reactivation of endogenous varicella-zoster virus (VZV) in dorsal sensory or cranial nerve ganglia. Rarely, this infection manifests without the characteristic dermatomal rash, a condition termed zoster sine herpete. Viral spreading of herpes zoster in the head and neck may manifest as various signs and symptoms because of the multiple possible combinations of cranial neuropathies. With only six cases reported in the English literature up to now, isolated neuropathies of the vagus nerve in the absence of cutaneous lesions tend to be misdiagnosed as idiopathic laryngeal paralysis...
September 2015: Journal of Voice: Official Journal of the Voice Foundation
https://www.readbyqxmd.com/read/25710617/gonadotropin-releasing-hormone-agonist-use-to-guide-diagnosis-and-treatment-of-autoimmune-progesterone-dermatitis
#12
Amy Domeyer-Klenske, Diana Robillard, John Pulvino, Daniel Spratt
BACKGROUND: Autoimmune progesterone dermatitis is a catamenial disorder traditionally diagnosed by subcutaneous or intramuscular progesterone challenge. Little has been reported regarding the use of a gonadotropin-releasing hormone (GnRH) agonist with a progestin add-back challenge to diagnose and guide management of this condition. CASE: A 50-year-old premenopausal woman presented with cyclic facial rash minimally responsive to standard treatment. Symptoms improved with depot leuprolide acetate and worsened with add-back progesterone therapy...
May 2015: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/25660362/beneficial-effects-of-bone-marrow-derived-mesenchymal-stem-cell-transplantation-in-a-non-immune-model-of-demyelination
#13
Gehan El-Akabawy, Laila Ahmed Rashed
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss throughout the central nervous system. Most of the previous studies that have been conducted to evaluate the efficacy of mesenchymal stem cells (MSCs) have utilized immune models such as experimental autoimmune encephalomyelitis (EAE). However, with this experimental setting, it is not clear whether the MSCs exert the functional improvement via an indirect consequence of MSC-mediated immunomodulation or via a direct replacement of the lost cells, paracrine actions, and/or an enhancement of endogenous repair...
March 2015: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/25115772/the-effect-of-glucagon-like-peptide-1-in-the-management-of-diabetes-mellitus-cellular-and-molecular-mechanisms
#14
Mohamed Lotfy, Jaipaul Singh, Hameed Rashed, Saeed Tariq, Erika Zilahi, Ernest Adeghate
Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin...
November 2014: Cell and Tissue Research
https://www.readbyqxmd.com/read/24940500/phase-i-trial-of-m2es-a-novel-polyethylene-glycosylated-recombinant-human-endostatin-plus-gemcitabine-in-advanced-pancreatic-cancer
#15
Yang Chen, Yiqi DU, Ping Li, Fei Wu, Yan Fu, Zhaoshen Li, Yongzhang Luo
Pancreatic cancer is one of the most lethal and resistant to treatment of solid tumors. Combination therapies with various types of drugs against pancreatic cancer have been extensively investigated. Endostatin is a potent endogenous inhibitor of angiogenesis, which may be administered in combination with various chemotherapeutic agents in the treatment of several types of cancer. To the best of our knowledge, this phase I trial was the first clinical study to determine the tolerance, safety and efficacy of M2ES, a novel polyethylene glycosylated recombinant human endostatin, administered concurrently with full-dose gemcitabine in patients with inoperable, locally advanced or metastatic pancreatic adenocarcinoma...
July 2014: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/24816557/staphylococcal-toxic-shock-syndrome-superantigen-mediated-enhancement-of-endotoxin-shock-and-adaptive-immune-suppression
#16
REVIEW
Katarina Kulhankova, Jessica King, Wilmara Salgado-Pabón
Infectious diseases caused by Staphylococcus aureus present a significant clinical and public health problem. S. aureus causes some of the most severe hospital-associated and community-acquired illnesses. Specifically, it is the leading cause of infective endocarditis and osteomyelitis, and the second leading cause of sepsis in the USA. While pathogenesis of S. aureus infections is at the center of current research, many questions remain about the mechanisms underlying staphylococcal toxic shock syndrome (TSS) and associated adaptive immune suppression...
August 2014: Immunologic Research
https://www.readbyqxmd.com/read/24678969/discovery-of-a-novel-series-of-orally-active-nociceptin-orphanin-fq-nop-receptor-antagonists-based-on-a-dihydrospiro-piperidine-4-7-thieno-2-3-c-pyran-scaffold
#17
Miguel A Toledo, Concepción Pedregal, Celia Lafuente, Nuria Diaz, Maria Angeles Martinez-Grau, Alma Jiménez, Ana Benito, Alicia Torrado, Carlos Mateos, Elizabeth M Joshi, Steven D Kahl, Karen S Rash, Daniel R Mudra, Vanessa N Barth, David B Shaw, David McKinzie, Jeffrey M Witkin, Michael A Statnick
Nociceptin/OFQ (N/OFQ) is a 17 amino acid peptide that is the endogenous ligand for the ORL1/NOP receptor. Nociceptin appears to regulate a host of physiological functions such as biological reactions to stress, anxiety, mood, and drug abuse, in addition to feeding behaviors. To develop tools to study the function of nociceptin and NOP receptor, our research effort sought to identify orally available NOP antagonists. Our effort led to the discovery of a novel chemical series based on the dihydrospiro(piperidine-4,7'-thieno[2,3-c]pyran) scaffold...
April 24, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/24665302/antiepileptic-drug-related-adverse-reactions-and-factors-influencing-these-reactions
#18
Parvaneh Karimzadeh, Vahid Bakrani
OBJECTIVE: According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. MATERIAL & METHODS: In this descriptive study, children less than 14 years old with AED side effects referred to the Children's Medical Center and Mofid Childeren's Hospital (Tehran, Iran) were evaluated during 2010-2012...
2013: Iranian Journal of Child Neurology
https://www.readbyqxmd.com/read/24470919/gianotti-crosti-syndrome-pityriasis-rosea-asymmetrical-periflexural-exanthem-unilateral-mediothoracic-exanthem-eruptive-pseudoangiomatosis-and-papular-purpuric-gloves-and-socks-syndrome-a-brief-review-and-arguments-for-diagnostic-criteria
#19
REVIEW
Antonio Chuh, Vijay Zawar, Michelle Law, Gabriel Sciallis
Several exanthems including Gianotti-Crosti syndrome, pityriasis rosea, asymmetrical periflexural exanthem, eruptive pseudoangiomatosis, and papular-purpuric gloves and socks syndrome are suspected to be caused by viruses. These viruses are potentially dangerous. Gianotti-Crosti syndrome is related to hepatitis B virus infection which is the commonest cause of hepatocellular carcinoma, and Epstein-Barr virus infection which is related to nasopharyngeal carcinoma. Pityriasis rosea has been suspected to be related to human herpesvirus 7 and 8 infections, with the significance of the former still largely unknown, and the latter being a known cause of Kaposi's sarcoma...
January 2, 2012: Infectious Disease Reports
https://www.readbyqxmd.com/read/24353307/mechanism-of-the-beneficial-and-protective-effects-of-exenatide-in-diabetic-rats
#20
Mohamed Lotfy, Jaipaul Singh, Hameed Rashed, Saeed Tariq, Erika Zilahi, Ernest Adeghate
Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes...
March 2014: Journal of Endocrinology
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