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https://www.readbyqxmd.com/read/30120858/current-and-investigational-agents-targeting-the-phosphoinositide-3-kinase-pathway
#1
Laura A Tang, Brianne N Dixon, Kathryn T Maples, Kristen M Poppiti, Tim J Peterson
Prevalent molecular alterations of the phosphoinositide 3-kinase (PI3K) pathway are found on solid tumors and are expressed in leukocytes, making it a desirable target in both solid and hematologic malignancies. In recent years, two agents targeting this pathway have been approved by the United States Food and Drug Administration, idelalisib and copanlisib, with many others under investigation. Due to the off-target effects seen with these agents, those under development have varying isoform specificity that mitigate toxicity...
August 18, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/30120478/fixed-low-dose-triple-combination-antihypertensive-medication-vs-usual-care-for-blood-pressure-control-in-patients-with-mild-to-moderate-hypertension-in-sri-lanka-a-randomized-clinical-trial
#2
Ruth Webster, Abdul Salam, H Asita de Silva, Vanessa Selak, Sandrine Stepien, Senaka Rajapakse, Stanley Amarasekara, Naomali Amarasena, Laurent Billot, Arjuna P de Silva, Mervyn Fernando, Rama Guggilla, Stephen Jan, Jayanthimala Jayawardena, Pallab K Maulik, Sepalika Mendis, Suresh Mendis, Janake Munasinghe, Nitish Naik, Dorairaj Prabhakaran, Gotabaya Ranasinghe, Simon Thom, Nirmali Tisserra, Vajira Senaratne, Sanjeewa Wijekoon, Santharaj Wijeyasingam, Anthony Rodgers, Anushka Patel
Importance: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. Objective: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. Design, Setting, and Participants: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy...
August 14, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/30120163/fda-approval-summary-pembrolizumab-for-recurrent-locally-advanced-or-metastatic-gastric-or-gastroesophageal-junction-adenocarcinoma-expressing-pd-l1
#3
Lola Fashoyin-Aje, Martha Donoghue, Huanyu Chen, Kun He, Janaki Veeraraghavan, Kirsten B Goldberg, Patricia Keegan, Amy E McKee, Richard Pazdur
On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab (Keytruda, Merck & Co., Inc., Whitehouse Station, NJ) for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy, and whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test...
August 17, 2018: Oncologist
https://www.readbyqxmd.com/read/30120160/fda-approval-summary-vemurafenib-for-the-treatment-of-patients-with-erdheim-chester-disease-with-the-braf-v600-mutation
#4
Patricia A Oneal, Virginia Kwitkowski, Lola Luo, Yuan Li Shen, Sriram Subramaniam, Stacy Shord, Kirsten B Goldberg, Amy E McKee, Edvardas Kaminskas, Ann Farrell, Richard Pazdur
On November 6, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of adult patients with Erdheim-Chester disease (ECD) with BRAF V600 mutation. ECD is a type of histiocytosis, a rare disorder characterized by an abnormal accumulation and behavior of cells of the mononuclear phagocytic system, which includes antigen-processing cells, dendritic cells, monocytes, or macrophages. Recently published data confirm a frequency of 54% of BRAF V600E mutations in patients with ECD...
August 17, 2018: Oncologist
https://www.readbyqxmd.com/read/30120013/management-of-immune-checkpoint-inhibitor-toxicities-a-review-and-clinical-guideline-for-emergency-physicians
#5
Adam T Hryniewicki, Claire Wang, Rebecca A Shatsky, Christopher J Coyne
BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of drugs used in cancer immunotherapy that are becoming more commonly used among advanced-stage cancers. Unfortunately, these therapies are sometimes associated with often subtle, potentially fatal immune-related adverse events (irAEs). OBJECTIVES: We conducted a review of relevant primary research and clinical guidelines in oncology, pharmacology, and other literature, and synthesized this information to address the needs of the emergency physician in the acute management of irAEs...
August 14, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/30119866/injection-technique-in-neurotoxins-and-fillers-indications-products-and-outcomes
#6
REVIEW
Murad Alam, Rebecca Tung
Injectable fillers and neuromodulators are used for a range of indications pertaining to the correction of facial aging and disfigurement. Fillers can correct soft tissue loss, depressed scars, and atrophy or asymmetry induced by systemic or local disease. Neuromodulators correct muscle-mediated skin creases, reshape the face, and address right-left functional asymmetry. Among the prepackaged injectable fillers approved by the US Food and Drug administration are hyaluronic acid derivatives, calcium hydroxylapatite, and poly-L-lactic acid; neuromodulators include three types of botulinum toxin type A and one type of type B...
September 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/30119677/six-month-safety-evaluation-of-robenacoxib-tablets-onsior%C3%A2-in-dogs-after-daily-oral-administrations
#7
Céline E Toutain, Patrick Brossard, Stephen B King, Rainer Helbig
BACKGROUND: Robenacoxib is a non-steroidal anti-inflammatory drug available for canine and feline use for the control of pain and inflammation marketed as Onsior™. The aim of this target animal safety study was to evaluate the 6-month safety profile of oral robenacoxib administration. It was a randomized, negative-controlled, parallel group study. Thirty-two healthy, young, experimentally naïve, purebred Beagle dogs were administered 0 (sham control, Group 1), 2, 6, and 10 mg/kg robenacoxib (corresponding to the upper end of the dosage range [1X, Group 2] and multiples thereof [3X and 5X, Group 3 and 4]), orally once daily for 6 months...
August 17, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/30119251/involvement-of-organic-cation-transporter-2-in-the-metformin-associated-increased-lactate-levels-caused-by-contrast-induced-nephropathy
#8
Shilei Yang, Yongguo Dai, Zhihao Liu, Changyuan Wang, Qiang Meng, Xiaokui Huo, Huijun Sun, Xiaodong Ma, Jinyong Peng, Kexin Liu
The application of iodinated contrast medium has become a risk factor for metformin-associated lactic acidosis (MALA), which leads to the accumulation of metformin in vivo is one of the principal reasons for MALA. However, the molecular mechanism of the adverse event is not yet clear. In this study, iohexol injection was used as a model drug. The contrast agent acute kidney injury rat model, in vivo rat pharmacokinetic study, kidney slices and HK-2 cells were performed to elucidate the pharmacokinetic molecular mechanism of accumulation of metformin caused by contrast-induced nephropathy (CIN)...
July 30, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119187/protective-effect-of-rotula-aquatica-lour-against-gentamicin-induced-oxidative-stress-and-nephrotoxicity-in-wistar-rats
#9
Vysakh A, Abhilash S, Jayesh Kuriakose, Sebastian Jose Midhun, Mathew Jyothis, M S Latha
Gentamicin is an aminoglycoside antibiotic widely used for the treatment of life-threatening infections caused by Gram-negative bacteria. The use of gentamicin was limited due to its ototoxic and nephrotoxic adverse effects. The current study was designed to evaluate the protective effect of ethyl acetate fraction from Rotula aquatica (EFRA) against gentamicin induced nephrotoxicity. The antioxidant enzymes status, lipid peroxidation, nitrate and ROS level, serum markers like creatinine, Urea, BUN were estimated in the present study...
July 18, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30118928/long-term-retention-rates-of-antiepileptic-drugs-used-in-acute-seizures
#10
Manuel Toledo, Elena Fonseca, Marta Olivé, Manuel Requena, Manuel Quintana, Laura Abraira-Del-Fresno, Xavier Salas-Puig, Estevo Santamarina
PURPOSE: A number of antiepileptic drugs (AEDs) are currently available for treating acute seizures. It is recommended to select the initial treatment option according to the type of epileptic syndrome and the patient's clinical characteristics, but little is known about the long-term retention rates of AEDs started in the emergency department. METHODS: We recruited patients admitted with seizures over a two-year period. All patients underwent early neurological assessment, EEG testing, and neuroimaging...
August 11, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/30118797/chst3-and-chst13-polymorphisms-as-predictors-of-bosentan-induced-liver-toxicity-in-japanese-patients-with-pulmonary-arterial-hypertension
#11
Kennosuke Yorifuji, Yuko Uemura, Shinji Horibata, Goh Tsuji, Yoko Suzuki, Kazuya Miyagawa, Kazuhiko Nakayama, Ken-Ichi Hirata, Shunichi Kumagai, Noriaki Emoto
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1,936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed...
August 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30118774/neuroprotective-effects-of-bergenin-in-alzheimer-s-disease-investigation-through-molecular-docking-in-vitro-and-in-vivo-studies
#12
Priyal Barai, Nisith Raval, Sanjeev Acharya, Ankit Borisa, Hardik Bhatt, Niyati Acharya
Alzheimer's disease (AD) is an enervating and chronic progressive neurodegenerative disorder, occurring frequently in the elderly and adversely affecting intellectual capabilities and the cognitive processes. Bergenin possesses efficacious antioxidant, antiulcerogenic, anti-HIV, hepatoprotective, neuroprotective, anti-inflammatory and immunomodulatory activity along with antinociceptive effect and wound healing properties. Previous studies have shown that bergenin has in vitro bovine adrenal tyrosine hydroxylase inhibitory activity, mushroom tyrosinase inhibitory activities, β-secretase (BACE-1) enzyme inhibitory activity and prevented neuronal death in the primary culture of rat cortical neurons...
August 14, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/30118739/pregabalin-and-lacosamide-ameliorate-paclitaxel-induced-peripheral-neuropathy-via-inhibition-of-jak-stat-signaling-pathway-and-notch-1-receptor
#13
Khaled F Al-Massri, Lamiaa A Ahmed, Hanan S El-Abhar
Anticonvulsant drugs such as pregabalin (PGB) and lacosamide (LCM), exhibit potent analgesic effects in diabetic neuropathy; however, their possible role/mechanisms in paclitaxel (PTX)-induced peripheral neuropathy have not been elucidated, which is the aim of the present study. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i. p) on days 0, 2, 4 and 6. Forty eight hours after the last dose of PTX, rats were treated orally with 30 mg/kg/day of either PGB or LCM for 21 days. Both therapies improved thermal hyperalgesia and cold allodynia induced by PTX...
August 14, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/30118457/effect-of-sequential-therapy-on-treatment-of-helicobacter-pylori-infection-in-children
#14
Seyed Mohsen Dehghani, Afsaneh Nazari, Hazhir Javaherizadeh
BACKGROUND: Helicobacter pylori infection which plays a major role in the etiology of chronic gastritis and duodenal ulcers in children and adults is one of the commonest chronic infection worldwide. Cure of the infection leads to healing of gastric inflammation and prevention of peptic ulcer. OBJECTIVE: The aim of this study was to evaluate the efficacy of the sequential therapy for treatment of Helicobacter pylori infection. MATERIALS AND METHODS: In this study, 40 children with symptoms of H...
April 2018: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/30118245/clinical-characteristics-of-exogenous-progestogen-hypersensitivity
#15
Eun-Jung Jo, Seung-Eun Lee, Hye-Kyung Park
BACKGROUND: Autoimmune progesterone dermatitis is a rare disease characterized by eruption recurrence in the luteal phase of each menstrual cycle. As synthetic progesterones are increasingly used for assisted reproductive techniques (ARTs) for infertility or prevention of abortion, cases of dermatitis caused by exogenous progesterone have been reported. OBJECTIVE: To investigate the clinical characteristics of exogenous progestogen hypersensitivity (PH). METHODS: We retrospectively reviewed data from patients presenting with dermatitis induced by exogenous progesterone between 2011 and 2016...
August 13, 2018: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/30117422/-detection-of-ugt1a1-6-single-nucleotide-polymorphism-in-oral-swap-samples-using-the-cascade-invader-assay-based-real-time-pcr
#16
Jie Yu Zhang, Ya Nan Chu, Bing Jie Zou, Yan Jie Zhang, Li Ying Feng
The adverse reaction to irinotecan is related to the single nucleotide polymorphism (SNP) of UGT1A1*6 genotype. The current SNP detection methods have various disadvantages, including time-consuming procedures, high- risk cross-contamination, and cumbersome operation. Hence, it is necessary to establish a new method suitable for clinical application, which is easy and simple to detect SNP with minimal risk for cross-contamination. In this study, a cascade invader assay-based real-time PCR, for UGT1A1*6 genotyping has been established by optimizing reaction conditions with DNA samples of three genotypes...
August 16, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/30117148/safety-surveillance-of-dietary-supplements-importance-challenges-and-new-horizons
#17
Scott A Jordan, Stephanie A Jack, Robert P Pless
Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems.1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements...
August 16, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30117129/non-compartmental-pharmacokinetics-and-safety-of-single-dose-eldecalcitol-ed-71-in-healthy-chinese-adult-males
#18
Qian Zhao, Hongzhong Liu, Ji Jiang, Yiwen Wu, Wen Zhong, Lili Li, Kazuhiro Miya, Masaichi Abe, Pei Hu
BACKGROUND AND OBJECTIVES: Eldecalcitol (ED-71) is a novel active vitamin D3 derivative, used for the treatment of osteoporosis. This is the first clinical study to investigate the pharmacokinetics and safety of eldecalcitol in Chinese subjects. METHODS: This was an open, single-center, randomized, two-dose level, two-period crossover phase I study in 24 healthy Chinese adult males. Eligible subjects received a single oral dose of eldecalcitol capsule 0.5 or 0.75 μg at period 1 or period 2, monitored over a 144-h observation period for pharmacokinetics and a 14-day observation period for safety...
August 16, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/30117103/targeting-axon-integrity-to-prevent-chemotherapy-induced-peripheral-neuropathy
#19
Virendra Bhagawan Chine, Ngan Pan Bennett Au, Gajendra Kumar, Chi Him Eddie Ma
Chemotherapy-induced peripheral neuropathy (CIPN) is an irreversible off-target adverse effect of many chemotherapeutic agents such as paclitaxel, yet its mechanism is poorly understood and no preventative measure is available. CIPN is characterized by peripheral nerve damages resulting in permanent sensory function deficits. Our recent unbiased genome-wide analysis revealed that heat shock protein (Hsp) 27 is part of a transcriptional network induced by axonal injury and highly enriched for genes involved in adaptive neuronal responses, particularly axonal regeneration...
August 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30117096/interactions-of-mexiletine-with-novel-antiepileptic-drugs-in-the-maximal-electroshock-test-in-mice-an-isobolographic-analysis
#20
Dorota Wróblewska, Monika Rudkowska, Monika Banach, Kinga K Borowicz-Reutt
The aim of the study was to evaluate precisely the type of interactions between mexiletine (an antiarrhythmic drug) and four new generation antiepileptic drugs: lamotrigine, oxcarbazepine, topiramate and pregabalin in the maximal electroshock test in mice (MES). The isobolographic analysis was used to assess the nature of interactions between the tested drugs. Total brain concentrations of antiepileptics were also measured to detect possible pharmacokinetic interactions. The results obtained indicated that the mixture of mexiletine and pregabalin at the fixed ratios of 1:1 and 3:1 led to supra-additive interaction in terms of seizure suppression, while the proportion of 1:3 occurred additive...
August 16, 2018: Neurochemical Research
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