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https://www.readbyqxmd.com/read/27920819/co-administration-of-metformin-and-n-acetylcysteine-with-dietary-control-improves-the-biochemical-and-histological-manifestations-in-rats-with-non-alcoholic-fatty-liver
#1
Naglaa Mohamed El-Lakkany, Sayed Hassan Seif El-Din, Abdel-Nasser Abdel-Aal Sabra, Olfat Ali Hammam, Fatma Abdel-Latif Ebeid
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27920684/worsening-of-lymphopenia-during-apremilast-treatment
#2
Antonios G A Kolios, Lars E French, Alexander A Navarini
Apremilast is an oral phosphodiesterase IV inhibitor recently registered for the treatment of psoriasis and psoriatic arthritis in Switzerland and other countries. Even though it offers only moderate efficacy compared to biologics, many patients prefer drugs given by the oral route. Apremilast is frequently used in private practice, as it showed no relevant safety signals in clinical trials and often, laboratory tests are omitted completely. Here we report a patient who developed acute lymphopenia and worsening of psoriasis during apremilast treatment, which resolved with discontinuation of apremilast...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/27920531/in-vitro-evaluation-of-folic-acid-conjugated-redox-responsive-mesoporous-silica-nanoparticles-for-the-delivery-of-cisplatin
#3
Merlis P Alvarez-Berríos, Juan L Vivero-Escoto
The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920128/forward-and-backward-pressure-waveform-morphology-in-hypertension
#4
Ye Li, Haotian Gu, Henry Fok, Jordi Alastruey, Philip Chowienczyk
We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4...
December 5, 2016: Hypertension
https://www.readbyqxmd.com/read/27919957/simultaneous-administration-of-statins-and-pioglitazone-limits-tumor-growth-in-a-rat-model-of-malignant-glioma
#5
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919611/discovery-of-4-sulfamoyl-phenyl-%C3%AE-lactams-as-a-new-class-of-potent-carbonic-anhydrase-isoforms-i-ii-iv-and-vii-inhibitors-the-first-example-of-subnanomolar-ca-iv-inhibitors
#6
Srinivas Angapelly, P V Sri Ramya, Andrea Angeli, Simona Maria Monti, Martina Buonanno, Mallika Alvala, Cladiu T Supuran, Mohammed Arifuddin
A series of benzenesulfonamides incorporating 1,3,4-trisubstituted-β-lactam moieties was prepared from sulfanilamide Schiff bases and in situ obtained ketenes, by using the Staudinger cycloaddition reaction. The new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) involved in various physiological/pathological conditions, hCA I, II, IV and VII. Excellent inhibitory activity was observed against all these isoforms, as follows: hCA I, involved in some eye diseases was inhibited with KIs in the range of 7...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27917692/once-daily-high-dose-tigecycline-pharmacokinetic-pharmacodynamic-based-dosing-for-optimal-clinical-effectiveness-dosing-matters-revisited
#7
Burke A Cunha, Jeffrey Baron, Cheston B Cunha
Tigecycline has emerged as first line therapy for serious systemic infections due to important pathogens (except P. aeruginosa and Proteus sp.), including multi-drug resistant (MDR) and Gram negative bacilli (GNB), including carbapenem resistant Enterobacteriae. Tigecycline has a "low resistance potential," is protective against C. difficile, and is often the only antibiotic effective against MDR GNB, e.g., Klebsiella sp. Areas covered: Standard dose tigecycline therapy has been used for intra-abdominal infections, complicated skin/skin structure infections (cSSSIs), and CAP...
December 3, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27916843/evaluation-and-comparison-of-the-inhibition-effect-of-astragaloside-iv-and-aglycone-cycloastragenol-on-various-udp-glucuronosyltransferase-ugt-isoforms
#8
Ruixue Ran, Chunze Zhang, Rongshan Li, Bowei Chen, Weihua Zhang, Zhenying Zhao, Zhiwei Fu, Zuo Du, Xiaolang Du, Xiaolong Yang, Zhongze Fang
As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in this article was carried out to investigate the inhibition effects of AST and CAG on UDP-glucuronosyltransferases (UGTs) to explore potential clinical toxicity. An in vitro UGTs incubation mixture was employed to study the inhibition of AST and CAG towards UGT isoforms...
November 29, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27916694/regenerated-cellulose-capsules-for-controlled-drug-delivery-part-iv-in-vitro-evaluation-of-novel-self-pore-forming-regenerated-cellulose-capsules
#9
Bhavik Bhatt, Vijay Kumar
In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC capsules were fabricated using a modified dip-coating approach, which yielded an assembled dosage form that was equivalent in size and shape to a conventional gelatin two-piece hard shell capsule. Drug release characteristics from RC capsules were evaluated using potassium chloride, diphenhydramine hydrochloride, tramadol hydrochloride, niacinamide, acetaminophen and ketoprofen as model APIs...
December 1, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27916450/dramatic-response-after-functional-hemispherectomy-in-a-patient-with-epileptic-encephalopathy-carrying-a-de-novo-col4a1-mutation
#10
Naomi Hino-Fukuyo, Atsuo Kikuchi, Masaki Iwasaki, Yuko Sato, Yuki Kubota, Tomoko Kobayashi, Tojo Nakayama, Kazuhiro Haginoya, Natsuko Arai-Ichinoi, Tetsuya Niihori, Ryo Sato, Tasuku Suzuki, Hiroki Kudo, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Shigeo Kure
We describe the first case of a successful functional hemispherectomy in a patient with epileptic encephalopathy and a de novo collagen type IV alpha 1 (COL4A1) mutation. A 4-year-old girl was COL4A1 mutation-positive and suffered from drug-resistant epilepsy, hemiplegia, and developmental delay. Magnetic resonance imaging detected no porencephaly, and she had no cataract or renal abnormality. Following a presurgical evaluation for epilepsy, she underwent a functional hemispherectomy. She has been seizure free with no intracranial hemorrhage or other perioperative complications...
December 1, 2016: Brain & Development
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#11
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#12
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27909950/hatt-a-phase-iv-single-arm-open-label-study-of-sorafenib-in-taiwanese-patients-with-advanced-hepatocellular-carcinoma
#13
Shi-Ming Lin, Sheng-Nan Lu, Ping-Tsung Chen, Long-Bin Jeng, Shinn-Cherng Chen, Chi-Tan Hu, Sien-Sing Yang, Marie-Aude Le Berre, Xuan Liu, David Y Mitchell, Klaas Prins, Joachim Grevel, Carol A E Peña, Gerold Meinhardt
BACKGROUND: Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. METHODS: All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients...
December 1, 2016: Hepatology International
https://www.readbyqxmd.com/read/27905516/discovery-and-structural-characterisation-of-new-fold-type-iv-transaminases-exemplify-the-diversity-of-this-enzyme-fold
#14
Tea Pavkov-Keller, Gernot A Strohmeier, Matthias Diepold, Wilco Peeters, Natascha Smeets, Martin Schürmann, Karl Gruber, Helmut Schwab, Kerstin Steiner
Transaminases are useful biocatalysts for the production of amino acids and chiral amines as intermediates for a broad range of drugs and fine chemicals. Here, we describe the discovery and characterisation of new transaminases from microorganisms which were enriched in selective media containing (R)-amines as sole nitrogen source. While most of the candidate proteins were clearly assigned to known subgroups of the fold IV family of PLP-dependent enzymes by sequence analysis and characterisation of their substrate specificity, some of them did not fit to any of these groups...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904818/the-government-s-role-in-regulating-coordinating-and-standardizing-the-response-to-alzheimer-s-disease-anticipated-international-cooperation-in-the-area-of-intractable-and-rare-diseases
#15
REVIEW
Qi Tang, Peipei Song, Lingzhong Xu
The World Health Organization (WHO) has emphasized that aging of the population is inextricably linked to many other global public health issues, such as universal health coverage, non-communicable diseases, and disability. However, Alzheimer's Disease International (ADI) estimates that 46.8 million elderly people worldwide were living with dementia in 2015. Alzheimer's disease (AD), the most common form of dementia, is one of the most common neurodegenerative diseases and is the main cause of cognitive impairment...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27903228/synthesis-and-evaluation-of-the-hypoglycemic-and-hypolipidemic-activity-of-novel-sulfonamide-benzothiazole-derivatives-of-benzylidene-2-4-thiazolidnedione
#16
Abbas Ahmadi, Mohsen Khalili, Lida Sohrabi, Nazanin Delzendeh, Babak Nahri-Niknafs, Fariba Ansari
Thiazolidinediones (TZDs) and sulfonamides are important and highly consumption class of antidiabetic drugs having insulin sensitizing and stimulating properties in patients with type 2 diabetes, respectively. In this paper, some novel benzothiazole derivatives of TZD-sulfonamides were synthesized (I-IV) and evaluated for anti-hyperglycemic and anti-hyperlipidemic activities in the STZ-induced diabetic rat model. Results indicated that all new conjugated drugs showed significant hypoglycemic activities compared to the control animals that were better for I and IV than others...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27902462/the-synthetic-lethal-killing-of-rad54b-deficient-colorectal-cancer-cells-by-parp1-inhibition-is-enhanced-with-sod1-inhibition
#17
Erin N McAndrew, Chloe C Lepage, Kirk J McManus
Colorectal cancer (CRC) is a leading cause of cancer-related death throughout the world. Despite improved screening efforts, most CRCs are diagnosed at late stages when surgery alone is not curative. Moreover, the low 5-year survival rate (~8-13%) for those living with stage IV CRC highlights the need for better treatment options. Many current chemotherapeutic approaches are non-specific and associated with side effects due to their tendency to target both normal and cancer cells. To address this issue, synthetic lethal (SL) approaches are now being explored in cancer and are defined as the lethal combination of two independently viable mutations/deletions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900570/concomitant-use-of-statins-in-tocilizumab-treated-patients-with-rheumatoid-arthritis-a-post-hoc-analysis
#18
Martin Soubrier, Jinglan Pei, Frédérick Durand, Lars Gullestad, Ani John
INTRODUCTION: Patients with rheumatoid arthritis (RA) have decreased survival because of increased cardiovascular risk compared with the general population, and treatment with tocilizumab (TCZ) has been shown to increase lipid levels; however, the relationship between lipids and cardiovascular risk is unknown. This post hoc analysis expanded on previously reported 24-week results by characterizing statin use and subsequent changes in lipid parameters in patients with RA treated with intravenous or subcutaneous TCZ (TCZ-IV or TCZ-SC) over 2 years of treatment...
November 29, 2016: Rheumatology and Therapy
https://www.readbyqxmd.com/read/27899776/-new-classification-for-advanced-colorectal-cancer-using-cancerplex%C3%A2-genomic-tests
#19
Hitoshi Kameyama, Yoshifumi Shimada, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Shujiro Okuda, Yiwei Ling, Hiroshi Izutsu, Keisuke Kodama, Mitsutaka Nakada, Toshifumi Wakai
Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®)...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27899086/closantel-a-veterinary-drug-with-potential-severe-morbidity-in-humans
#20
Seyed Ali Tabatabaei, Mohammad Soleimani, Mohammad Reza Mansouri, Ahmad Mirshahi, Bahman Inanlou, Mojtaba Abrishami, Ahmad Reza Pakrah, Hamideh Masarat
BACKGROUND: Closantel is a halogenated salicylanilide with a potent anti parasitic activity. It is widely used in management of parasitic infestation in animals, but is contraindicated in humans. CASE PRESENTATION: A 34-year-old man with depression was referred to our center with progressive loss of vision in both eyes 10 days after unintentional ingestion of three 500 mg tablets of Closantel. On fundus examination, left optic disc margin was blurred. His bilateral visual acuity was no light perception (NLP) despite prescribed IV erythropoietin injections 20,000 units daily for 3 days and 1gr intravenous methylprednisolone acetate for 3 days followed by 1 mg/kg oral prednisolone...
November 29, 2016: BMC Ophthalmology
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