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https://www.readbyqxmd.com/read/27922495/toxic-and-endocrine-myopathies
#1
Hans D Katzberg, Charles D Kassardjian
PURPOSE OF REVIEW: This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. RECENT FINDINGS: Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#2
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919256/the-return-of-chloroquine-susceptible-plasmodium-falciparum-malaria-in-zambia
#3
Sydney Mwanza, Sudhaunshu Joshi, Michael Nambozi, Justin Chileshe, Phidelis Malunga, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Christine Manyando, Modest Mulenga, Miriam Laufer
BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy...
December 5, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27916837/chloroquine-an-endocytosis-blocking-agent-inhibits-zika-virus-infection-in-different-cell-models
#4
Rodrigo Delvecchio, Luiza M Higa, Paula Pezzuto, Ana Luiza Valadão, Patrícia P Garcez, Fábio L Monteiro, Erick C Loiola, André A Dias, Fábio J M Silva, Matthew T Aliota, Elizabeth A Caine, Jorge E Osorio, Maria Bellio, David H O'Connor, Stevens Rehen, Renato Santana de Aguiar, Andrea Savarino, Loraine Campanati, Amilcar Tanuri
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres...
November 29, 2016: Viruses
https://www.readbyqxmd.com/read/27914754/antiparasitic-and-disease-modifying-activity-of-nyctanthes-arbor-tristis-linn-in-malaria-an-exploratory-clinical-study
#5
Chhaya S Godse, Prakash S Tathed, Sameer S Talwalkar, Rama A Vaidya, Ashok J Amonkar, Akhil B Vaidya, Ashok D B Vaidya
BACKGROUND: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthesarbor-tristis Linn. - (Parijat) had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study. OBJECTIVE: To further explore antimalarial potential of the plant through additional objective markers...
November 30, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27913816/genetic-ablation-or-pharmacologic-inhibition-of-autophagy-mitigated-nsaid-associated-gastric-damages
#6
Chan Young Ock, Jong-Min Park, Young-Min Han, Migyeong Jeong, Mi-Young Kim, Ho Jae Lee, Ki Baik Hahm
: Non-steroidal anti-inflammatory drug (NSAID)-associated endoplasmic reticulum (ER) stress (a cyclooxygenase-2-independent mechanism) and consequent autophagic cell death are responsible for NSAID-associated gastric damage. Therefore, alleviating cytotoxicity executed via ER stress and autophagy can be a strategy to prevent NSAID-associated gastric damage. Here, we explored whether genetic or pharmacologic inhibition of autophagy can mitigate NSAID-associated gastric damage in in vitro and in vivo models...
December 2, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27912145/chloroquine-cq-exerts-anti-breast-cancer-through-modulating-microenvironment-and-inducing-apoptosis
#7
Yanjun Zhang, Yu Cao, Xiaodan Sun, Yonghui Feng, Yunting Du, Fei Liu, Chunyun Yu, Feng Jin
CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#8
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27907019/the-effects-of-transdermally-delivered-oleanolic-acid-on-malaria-parasites-and-blood-glucose-homeostasis-in-p-berghei-infected-male-sprague-dawley-rats
#9
Happiness P Sibiya, Musa V Mabandla, Cephas T Musabayane
The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of P. berghei-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period...
2016: PloS One
https://www.readbyqxmd.com/read/27905330/screening-for-chloroquine-maculopathy-in-populations-with-uncertain-reliability-in-outcomes-of-automatic-visual-field-testing
#10
Paradee Kunavisarut, Pimploy Chavengsaksongkram, Aniki Rothova, Kessara Pathanapitoon
PURPOSE: The purpose of this study was to compare screening methods for the early detection of maculopathy in patients treated with chloroquine (CQ) or hydroxychloroquine (HCQ) and to identify the risk factors for the development of toxic maculopathy. METHODS: We performed a prospective study of all 217 patients taking CQ and/or HCQ and seen in our center between July 2011 and December 2013. All subjects underwent a complete ocular examination, as well as spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and 10-2 Humphrey visual field (10-2 HVF)...
October 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27902742/chloroquine-sensitizes-nasopharyngeal-carcinoma-cells-but-not-nasoepithelial-cells-to-irradiation-by-blocking-autophagy
#11
Anna Makowska, Michael Eble, Kirsten Prescher, Mareike Hoß, Udo Kontny
BACKGROUND: Treatment of nasopharyngeal carcinoma requires the application of high dosages of radiation, leading to severe long-term complications in the majority of patients. Sensitizing tumor cells to radiation could be a means to increase the therapeutic window of radiation. Nasopharyngeal carcinoma cells display alterations in autophagy and blockade of autophagy has been shown to sensitize them against chemotherapy. METHODS: We investigated the effect of chloroquine, a known inhibitor of autophagy, on sensitization against radiation-induced apoptosis in a panel of five nasopharyngeal carcinoma cell lines and a SV40-transformed nasoepithelial cell line...
2016: PloS One
https://www.readbyqxmd.com/read/27899303/gambogic-acid-counteracts-mutant-p53-stability-by-inducing-autophagy
#12
Giorgia Foggetti, Laura Ottaggio, Debora Russo, Paola Monti, Paolo Degan, Gilberto Fronza, Paola Menichini
Mutant p53 (mutp53) proteins are frequently present at higher levels than the wild-type (wt) protein in tumors, and some of them can acquire oncogenic properties. Consistently, knockdown of mutp53 protein in human cancer cell lines leads to reduced cell proliferation and invasion as well as to an increased sensitivity to some anticancer drugs. Therefore, the exploitation of cellular pathways and/or molecules that promote mutp53 degradation may have a therapeutic interest. Recently, autophagy is emerging as an important pathway involved in the stability of mutp53...
November 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27899249/ginsenoside-20-s-rg3-induced-autophagy-to-inhibit-migration-and-invasion-of-ovarian-cancer
#13
Xia Zheng, Wei Chen, Huilian Hou, Jie Li, Huijin Li, Xiaomin Sun, Le Zhao, Xu Li
BACKGROUND: Autophagy maintains cellular homeostasis through engulfing cytoplasmic proteins and organelles, and plays an important role in cancer initiation and progression. Ginsenoside 20(S)-Rg3, an active ingredient of Panax ginseng, exerts anti-cancer functions in various cancers. However, its molecular mechanisms, including its effect on autophagy, are not fully elucidated in tumor models. METHODS: Ovarian cancer cell line SKOV3 was treated by various concentrations of 20(S)-Rg3...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27899115/characterizing-the-impact-of-sustained-sulfadoxine-pyrimethamine-use-upon-the-plasmodium-falciparum-population-in-malawi
#14
Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri, Anja Terlouw, Alister Craig, Susana Campino, Harold Ocholla, Taane G Clark
BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used...
November 29, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27896925/design-synthesis-and-in-vitro-antiplasmodial-activity-of-some-bisquinolines-against-chloroquine-resistant-strain
#15
Srinivasarao Kondaparla, Pooja Agarwal, Kumkum Srivastava, Sunil K Puri, S B Katti
A series of novel bisquinoline compounds comprising, N(1) -(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8 and 10.6 fold superior activity as compared to chloroquine (CQ) (IC50 = 0...
November 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27895479/cationic-pegylated-liposomes-incorporating-an-antimicrobial-peptide-tilapia-hepcidin-2-3-an-adjuvant-of-epirubicin-to-overcome-multidrug-resistance-in-cervical-cancer-cells
#16
Vivian Juang, Hsin-Pin Lee, Anya Maan-Yuh Lin, Yu-Li Lo
Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3 significantly increased the cytotoxicity of epirubicin...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27889859/chronic-high-dose-glucocorticoid-therapy-triggers-the-development-of-chronic-organ-damage-and-worsens-disease-outcome-in-systemic-lupus-erythematosus
#17
Tünde Tarr, Gábor Papp, Nikolett Nagy, Edina Cserép, Margit Zeher
Long-term survival of patients with systemic lupus erythematosus (SLE) improved worldwide; thus, prevention of cumulative organ damage became a major goal in disease management. The aim of our study was to investigate the chronic organ damages and their influence on disease outcome in SLE. We evaluated clinical conditions, laboratory findings and medications of 357 consecutive SLE patients and assessed their impact on Systemic Lupus Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease outcome...
November 26, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27889812/research-progress-of-hydroxychloroquine-and-autophagy-inhibitors-on-cancer
#18
REVIEW
Ting-Ting Shi, Xiao-Xu Yu, Li-Jun Yan, Hong-Tao Xiao
PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study...
November 26, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27889640/inhibition-of-autophagy-with-bafilomycin-and-chloroquine-decreases-mitochondrial-quality-and-bioenergetic-function-in-primary-neurons
#19
Matthew Redmann, Gloria A Benavides, Taylor F Berryhill, Willayat Y Wani, Xiaosen Ouyang, Michelle S Johnson, Saranya Ravi, Stephen Barnes, Victor M Darley-Usmar, Jianhua Zhang
Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics...
November 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/27889531/sirt1-protects-cardiac-cells-against-apoptosis-induced-by-zearalenone-or-its-metabolites-%C3%AE-and-%C3%AE-zearalenol-through-an-autophagy-dependent-pathway
#20
Intidhar Ben Salem, Manel Boussabbeh, Julie Pires Da Silva, Arnaud Guilbert, Hassen Bacha, Salwa Abid-Essefi, Christophe Lemaire
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2). We show that treatment with ZEN or its metabolites induces the activation of the mitochondrial pathway of apoptosis as characterized by an increase in ROS generation, a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspases...
November 23, 2016: Toxicology and Applied Pharmacology
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