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https://www.readbyqxmd.com/read/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#1
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29352512/trpv1-antagonists-that-cause-hypothermia-instead-of-hyperthermia-in-rodents-compounds-pharmacological-profiles-in-vivo-targets-thermoeffectors-recruited-and-implications-for-drug-development
#2
Andras Garami, Eszter Pakai, Heath A McDonald, Regina M Reilly, Arthur Gomtsyan, Joshua J Corrigan, Erika Pinter, Dawn X D Zhu, Sonya G Lehto, Narender R Gavva, Philip R Kym, Andrej A Romanovsky
AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice...
January 20, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29351567/whole-thorax-irradiation-of-non-human-primates-induces-persistent-nuclear-damage-and-gene-expression-changes-in-peripheral-blood-cells
#3
Shanaz A Ghandhi, Helen C Turner, Igor Shuryak, Gregory O Dugan, J Daniel Bourland, John D Olson, Janet A Tooze, Shad R Morton, Ines Batinic-Haberle, J Mark Cline, Sally A Amundson
We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals...
2018: PloS One
https://www.readbyqxmd.com/read/29351487/contribution-of-parasympathetic-muscarinic-augmentation-of-insulin-secretion-to-olanzapine-induced-hyperinsulinemia
#4
Michael R Rickels, Elys M Perez, Amy J Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels, Karen L Teff
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized fifteen healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet and activity controlled inpatient conditions...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29350420/over-expression-of-dec1-inhibits-myogenic-differentiation-by-modulating-myog-activity-in-bovine-satellite-cell
#5
Yongzhen Huang, Xinsheng Lai, Linyong Hu, Chuzhao Lei, Xianyong Lan, Chunlei Zhang, Yun Ma, Li Zheng, Yue-Yu Bai, Fengpeng Lin, Hong Chen
Differentiated embryo chondrocyte 1 (DEC1), a member of basic-helix-loop-helix transcription factor Bhlhe40, also called stimulated by retinoic acid 13, STRA13, plays an important role in the regulation of adipogenesis, tumorigenesis, peripheral circadian output, response to hypoxia and development of metabolic syndrome. Previous studies suggested that DEC1 was involved in skeletal muscle development; however, its precise role in myoblast differentiation has not been determined. In the present study, we showed that DEC1 expressed ubiquitously in different bovine tissues and was down-regulated in differentiated bovine satellite cells...
January 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29350104/the-importance-of-perfusion-index-monitoring-in-evaluating-the-efficacy-of-stellate-ganglion-blockage-treatment-in-raynaud-s-disease
#6
Ömer Fatih Şahin, Ebru Tarıkçı Kılıç, Yakup Aksoy, Ayhan Kaydu, Erhan Gökçek
Stellate ganglion blockage (SGB) is a method used for treating Raynaud's phenomenon (RP). This study primarily aimed to determine whether the perfusion index (PI) can be used an alternative to Horner's signs in evaluating the efficacy of SGB in patients diagnosed with RP. In a total of 40 patients, aged 18-65 years and diagnosed with primary RP, SGB was applied for 5 days on the same side with the 2-finger method, using 6 mL of 5% levobupivacaine at the 7th cervical vertebra level. The PI values were recorded from the distal end of the 2nd finger of the upper extremity on the side applied with the block at baseline and at 5, 15, 30, 60 and 120 min...
December 2018: Libyan Journal of Medicine
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#7
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29346131/toxicological-profile-and-safety-pharmacology-of-a-single-dose-of-fibroblast-activation-protein-%C3%AE-based-doxorubicin-prodrug-in-vitro-and-in-vivo-evaluation
#8
Sichao Huang, Yuchen Zhang, Jinsong Zhong, Ying Pan, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα...
January 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29339292/selective-hcn1-block-as-a-strategy-to-control-oxaliplatin-induced-neuropathy
#9
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29339027/a-comparative-study-of-osteopontin-and-mmp-2-protein-expression-in-peripheral-and-central-giant-cell-granuloma-of-the-jaws
#10
Nooshin Mohtasham, Nasrollah Saghravanian, Bahareh Fatemi, Mehdi Vahedi, Monavar Afzal-Aghaee, Hamideh Kadeh
INTRODUCTION: Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis. OBJECTIVE: The aim of this study was to compare matrix metalloproteinases-2 and osteopontin protein expression in the multinucleated giant cells and mononuclear cells of the peripheral and central giant cell granuloma lesions. METHODS: In this retrospective study, the presence of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were assessed by streptavidin-biotin immunohistochemistry...
December 27, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/29338149/injection-pressure-mapping-of-intraneural-vs-perineural-injections-further-lessons-from-cadaveric-studies
#11
Andrzej Krol, Arber Vala, Leonidas Phylactides, Matthew Szarko, Miguel A Reina, Jose de Andrés
BACKGROUND: The aim of the study was to investigate the difference between intraneural and perineural injection pressures in human cadavers. Targeted nerves included the cervical roots, the supraclavicular and infraclavicular brachial plexus, the sciatic-subgluteal nerve and the common peroneal and tibial nerves. METHODS: Ten readings were obtained for each nerve location. 1mL of 0.9% NaCl was injected over ten seconds - deliberately slower than in clinical practice to eliminate the risk of aberrant readings relating to the speed of injection...
January 16, 2018: Minerva Anestesiologica
https://www.readbyqxmd.com/read/29337680/in-vitro-assessment-of-the-cytotoxic-dna-damaging-and-cytogenetic-effects-of-hydroquinone-in-human-peripheral-blood-lymphocytes
#12
Karlo Jurica, Irena Brčić Karačonji, Vesna Benković, Nevenka Kopjar
This study investigated the mechanisms of hydroquinone toxicity and assessed the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 μg mL-1 in human peripheral blood lymphocytes exposed for 24 h. The outcomes of the treatments were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay. The tested hydroquinone concentrations produced relatively weak cytotoxicity in resting lymphocytes, which mostly died via apoptosis...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29337237/uridine-5-triphosphate-partially-blocks-differentiation-signals-and-favors-a-more-repair-state-in-cultured-rat-schwann-cells
#13
Marta Palomo-Guerrero, Jose Miguel Cosgaya, Alejandro Gella, Núria Casals, Carmen Grijota-Martinez
Schwann cells (SCs) play a key role in peripheral nerve regeneration. After damage, they respond acquiring a repair phenotype that allows them to proliferate, migrate and redirect axonal growth. Previous studies have shown that Uridine-5'-Triphosphate (UTP) and its purinergic receptors participate in several pathophysiological responses in the nervous system. Our group has previously described how UTP induces the migration of a Schwannoma cell line and promotes wound healing. These data suggest that UTP participates in the signaling involved in the regeneration process...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29336992/schwann-cell-lamellipodia-regulate-cell-cell-interactions-and-phagocytosis
#14
Johana Tello Velasquez, James A St John, Lynn Nazareth, Jenny A K Ekberg
Lamellipodia in Schwann cells (SCs) are crucial for myelination, but their other biological functions remain largely uncharacterised. Two types of lamellipodia exist in SCs: axial lamellipodia at the outermost edge of the cell processes, and radial lamellipodia appearing peripherally along the entire cell. We have previously shown that radial lamellipodia on olfactory glia (olfactory ensheathing cells; OECs) promote cell-cell adhesion, contact-mediated migration and phagocytosis. Here we have investigated whether lamellipodia in SCs have similar roles...
January 11, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29333980/percentages-of-pd-1-cd4-t-cells-and-pd-l1-dcs-are-increased-and-spd-1-level-is-elevated-in-patients-with-immune-thrombocytopenia
#15
Yingying Wang, Nannan Pang, Xinyou Wang, Ying Liu, Xiujuan Wang, Lei Wang, Mingling Sun, Halida Yasen, Fang Zhao, Wenxia Fan, Xinhong Guo, Jianbing Ding
The present study is to measure the expression of programmed death (PD)-1 / programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate their correlation with the secretion of cytokines. A total of 35 patients with ITP were included in the present study. Twenty healthy subjects who received physical examination at our hospital were included as control group. Peripheral blood was collected from all ITP patients and healthy subjects...
January 15, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#16
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
January 10, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#17
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330324/betaine-ameliorates-experimental-autoimmune-encephalomyelitis-by-inhibiting-dendritic-cell-derived-il-6-production-and-th17-differentiation
#18
Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao, Changsheng Du
IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29321320/hiv-1-specific-iga-monoclonal-antibodies-from-an-hiv-1-vaccinee-mediate-galcer-blocking-and-phagocytosis
#19
Saintedym Wills, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, Judith T Lucas, Robert Parks, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Rasmi Thomas, Jerome H Kim, Nelson L Michael, Merlin L Robb, Mike McRaven, David C Montefiori, Thomas J Hope, Hua-Xin Liao, M Anthony Moody, Guido Ferrari, Barton F Haynes, S Munir Alam, Mattia Bonsignori, Georgia D Tomaras
Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against HIV-1 acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and their capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope specific IgA monoclonal antibodies by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, non-recombinant IgA monoclonal antibodies (mAbs)...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321137/novel-function-of-ceramide-for-regulation-of-mitochondrial-atp-release-in-astrocytes
#20
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
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