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https://www.readbyqxmd.com/read/28647917/novel-endpoints-for-heart-failure-clinical-trials
#1
REVIEW
Carine E Hamo, Mihai Gheorghiade, Javed Butler
PURPOSE OF REVIEW: With the growing prevalence of heart failure, there is a particular need to develop new pharmacologic treatments that can improve outcomes. While there are several approved therapies for heart failure with reduced ejection fraction, there is currently no approved agent for those with preserved ejection fraction. The current review aimed to explore the utility of alternate endpoints to mortality and hospitalization. RECENT FINDINGS: There is increased interest in the use of alternative endpoints such as functional status and quality of life for heart failure drug development to focus on patients feeling better in addition to improving outcomes...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28647791/premonitory-symptoms-of-migraine-in-childhood-and-adolescence
#2
REVIEW
N Karsan, P Prabhakar, P J Goadsby
PURPOSE OF REVIEW: Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future...
July 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28647739/antipsychotic-induced-dopamine-supersensitivity-psychosis-pharmacology-criteria-and-therapy
#3
Guy Chouinard, Anne-Noël Samaha, Virginie-Anne Chouinard, Charles-Siegfried Peretti, Nobuhisa Kanahara, Masayuki Takase, Masaomi Iyo
The first-line treatment for psychotic disorders remains antipsychotic drugs with receptor antagonist properties at D2-like dopamine receptors. However, long-term administration of antipsychotics can upregulate D2 receptors and produce receptor supersensitivity manifested by behavioral supersensitivity to dopamine stimulation in animals, and movement disorders and supersensitivity psychosis (SP) in patients. Antipsychotic-induced SP was first described as the emergence of psychotic symptoms with tardive dyskinesia (TD) and a fall in prolactin levels following drug discontinuation...
June 24, 2017: Psychotherapy and Psychosomatics
https://www.readbyqxmd.com/read/28647652/kinase-activity-in-recurring-primary-skull-base-chordomas-and-chondrosarcomas-identification-of-novel-pathways-of-oncogenesis-and-potential-drug-targets
#4
Philip Tatman, Joshua Osbun, Youssef Yakkioui, Sumanpret Kaur, Carolina Parada, Tina Busald, Donald Born, Owais Ahmad, Jing Zhang, Manuel Ferreira
OBJECTIVE: Chordomas and chondrosarcomas are tumors that can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within five years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the FDA for chordomas or chondrosarcomas. The high propensity for recurrence and lack of definitive adjuvant therapy necessitates additional basic science research to identify molecular anomalies associated with recurrent disease...
June 21, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28647589/mannose-conjugated-layered-double-hydroxide-nanocomposite-for-targeted-sirna-delivery-to-enhanced-cancer-therapy
#5
Li Li, Run Zhang, Wenyi Gu, Zhi Ping Xu
Sheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moiety was firstly conjugated onto SiO2-coated LDH nanocomposite...
June 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28647568/hepatocyte-derived-macrophage-migration-inhibitory-factor-mediates-alcohol-induced-liver-injury-in-mice-and-patients
#6
Veronica Marin, Kyle Poulsen, Gemma Odena, Megan R McMullen, Jose Altamirano, Pau Sancho-Bru, Claudio Tiribelli, Juan Caballeria, Natalia Rosso, Ramon Bataller, Laura E Nagy
BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) is a multi-potent cytokine that contributes to the inflammatory response to injury. MIF is expressed by multiple cell types; however, the cellular source and actions of MIF in alcoholic liver disease (ALD) are not well known. Here we tested the hypothesis that non-myeloid cells, specifically hepatocytes, are an important cellular source of MIF in ALD. METHODS: MIF expression was measured in HuH7 and differentiated THP-1 cells in response to ethanol...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647541/response-tailored-protocol-versus-the-fixed-12weeks-of-dual-sofosbuvir-daclatasvir-treatment-in-egyptian-patients-with-chronic-hepatitis-c-genotype-4-infection-a-randomized-open-label-non-inferiority-trial
#7
Mostafa Yakoot, Alaa M Abdo, Siham Abdel-Rehim, Sherine Helmy
BACKGROUND: The most recent European Association for the Study of the Liver (EASL) 2016 Guidelines on treatment of hepatitis C (HCV), allowed for shortening the course of treatment for some subsets of patients with sofosbuvir/ledipasvir and with grazoprevir/elbasvir based on cutoff baseline HCV RNA values. We hypothesized that it would be prudent to also consider an objectively assuring very rapid, on-treatment, virologic response to therapy at week 2 (vRVR) before taking the decision of shortening the treatment duration...
May 17, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28647477/derivatives-of-alkyl-gallate-triphenylphosphonium-exhibit-antitumor-activity-in-a-syngeneic-murine-model-of-mammary-adenocarcinoma
#8
Liliana Peredo-Silva, Sebastián Fuentes-Retamal, Cristian Sandoval-Acuña, Mario Pavani, Juan D Maya, Vicente Castro-Castillo, Matías Madrid-Rojas, Solange Rebolledo, Ulrike Kemmerling, Eduardo Parra, Jorge Ferreira
We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP(+)C8, TPP(+)C10 and TPP(+)C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP(+)C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells...
June 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28647364/crystal-structures-of-the-isochorismatase-domains-from-vibrio-anguillarum
#9
Jiansen Du, Tian Deng, Qingjun Ma
Antibiotic resistance is becoming a global threat and overuse of antibiotics in aquaculture disease control worsens the situation. To reduce the risk of drug resistance developed in aquaculture, safer biocontrol programs are needed. Antivirulence therapy, with less chance for developing drug resistance, is a promising approach. To facilitate antivirulence inhibitor design against Vibrio anguillarum, a serious aquaculture pathogen, we present crystal structures for isochorismatase domains of AngB and VabB, which are required to synthesize siderophore, a critical virulence factor...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647277/risk-factors-for-nosocomial-infections-in-patients-receiving-extracorporeal-membrane-oxygenation-supportive-therapy
#10
Geqin Sun, Binfei Li, Haili Lan, Juan Wang, Lanfei Lu, Xueqin Feng, Xihua Luo, Haizhong Yan, Yuejing Mu
BACKGROUND AND OBJECTIVE: The aim of this study was to analyze risk factors for nosocomial infection (NI) in patients receiving extracorporeal membrane oxygenation (ECMO) support. PATIENTS AND METHODS: Clinical NI data were collected from patients who received ECMO support therapy, and analyzed retrospectively. RESULTS: Among 75 ECMO patients, 20 were found to have developed NI (infection rate 26.7%); a total of 58 pathogens were isolated, including 43 strains of gram-negative bacteria (74...
June 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28647110/success-of-tardive-electroconvulsive-therapy-sessions-after-loxapine-induced-malignant-syndrome-in-the-context-of-very-poor-metabolisation
#11
Juliette Descoeur, Laurent Philibert, Kevin Chalard, Jérôme Attal, Pierre Petit, Kada Klouche, Mathieu Olivier
We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours)...
May 29, 2017: Thérapie
https://www.readbyqxmd.com/read/28647107/-justification-of-off-label-antibiotics-uses-in-hospitalized-children
#12
Christelle Berthod, Behrouz Kassaï, Remy Boussageon, Léopold Adelaide, Matthias Jacquet-Lagrèze, Audrey Lajoinie
Unlicensed and off-label (UL/OL) drugs are commonly used in pediatrics wards, especially the antibiotics. It remains unclear if this strategy is justified by randomized controlled trials of good quality? OBJECTIVE: The aim of this study was to compare the level of evidence of UL/OL antibiotics prescription in hospitalized children. The initial hypothesis was that the UL/OL antibiotics prescriptions had a lower level of evidence than licensed antibiotics. METHOD: This observational study assessed the antibiotics prescription in the children mother and women hospital of Lyon...
May 26, 2017: Thérapie
https://www.readbyqxmd.com/read/28646952/drug-resistant-tuberculosis-primary-transmission-and-management
#13
Alexander C Outhred, Philip N Britton, Ben J Marais
The DOTS strategy assisted global tuberculosis (TB) control, but was unable to prevent the emergence and spread of drug-resistant strains. Genomic evidence confirms the transmission of drug-resistant Mycobacterium tuberculosis strains in many different settings, indicative of epidemic spread. These findings emphasise the need for enhanced infection control measures in health care and congregate settings. Young children in TB endemic areas are particularly vulnerable. Although advances in TB drug and vaccine development are urgently needed, improved access to currently available preventive therapy and treatment for drug resistant TB could reduce the disease burden and adverse outcomes experienced by children...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28646904/ct-findings-in-patients-with-cabazitaxel-induced-pelvic-pain-and-haematuria-a-case-series
#14
Geethal N Malalagama, Steve Chryssidis, Francis X Parnis
BACKGROUND: Haematuria and pelvic pain are recognized and documented adverse reactions related to Cabazitaxel use. To date there has not been any documentation of imaging findings in patients with this presentation. CASES: We report a case series of five patients who experienced these symptoms while on Cabazitaxel and were all found to have very similar urothelial changes on CT. The patients were noted to have ureteric and renal pelvic dilatation along with urothelial enhancement (in those who had post contrast imaging)...
June 24, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28646805/natural-cancer-therapy-and-prevention-targeted-on-cancer-cells-and-cancer-stem-cells-based-on-the-cytochrome-p45o-enzyme-cyp1b1-a-commentary
#15
William R Ware
The importance of the P450 enzyme CYP1B1 in both cancer therapy and prevention are reviewed and evidence is discussed, which provides strong biological plausibility for the therapeutic merits of this approach. The significant resistance to chemotherapy among common cancers, and the realization that in many cases chemotherapy leaves behind drug-resistant cancer cells that eventually cause recurrence and metastatic disease, has recently prompted the search for natural compounds that would circumvent this problem...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646699/insulin-and-the-polycystic-ovary-syndrome
#16
REVIEW
Djuro Macut, Jelica Bjekić-Macut, Dario Rahelić, Mirjana Doknić
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes...
June 12, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28646542/reconstitution-of-low-density-lipoproteins-with-fatty-acids-for-the-targeted-delivery-of-drugs-into-cancer-cells
#17
Chunlei Zhu, Pallab Pradhan, Da Huo, Jiajia Xue, Song Shen, Krishnendu Roy, Younan Xia
Low-density lipoproteins (LDLs) represent a novel class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. Here we report a facile procedure for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts...
June 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28646540/animal-embryotoxicity-studies-of-key-non-artemisinin-antimalarials-and-use-in-women-in-the-first-trimester
#18
REVIEW
Robert L Clark
The World Health Organization currently recommends quinine+clindamycin for use against malaria in the first trimester. This may soon change to recommending artemisinin-based combination therapies (standard duration of dosing = 3 days). The non-artemisinin partner drugs include amodiaquine, lumefantrine, mefloquine, piperaquine, sulfadoxine+pyrimethamine, and pyronaridine. For quinine, clindamycin, and mefloquine and the combinations of sulfadoxine+pyrimethamine and artemether+lumefantrine, there are reports (including studies without internal comparison groups) that combined describe 304 to >1100 exposures of women in the first trimester for each drug with no conclusive evidence of adverse effects on pregnancy at therapeutic doses...
June 24, 2017: Birth defects research
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#19
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646522/pericarditis-during-infliximab-therapy-in-paediatric-ulcerative-colitis
#20
V Dipasquale, S M C Gramaglia, M A Catena, C Romano
WHAT IS KNOWN AND STUDY OBJECTIVE: Infliximab is a widely used drug for treating inflammatory bowel disease (IBD). This drug is known to rarely cause pericarditis in adult populations. CASE SUMMARY: This report details the case of a 14-year-old boy with ulcerative colitis who developed pericarditis after a second infliximab infusion. After discontinuation of therapy, the patient's symptoms were resolved. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first reported paediatric case of pericarditis as a possible complication of infliximab therapy in IBD...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
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