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https://www.readbyqxmd.com/read/28235723/bypassing-multidrug-resistant-ovarian-cancer-using-ultrasound-responsive-doxorubicin-curcumin-co-deliver-alginate-nanodroplets
#1
Fatemeh Baghbani, Fathollah Moztarzadeh
Ultrasound-responsive perfluorocarbon nanoemulsions are a class of new multifunctional smart nanocarriers which combine diagnostic properties with therapeutic properties and release their drug payload in a controlled manner in response to ultrasound. Therefore, combination therapy using chemotherapeutic and chemosensitizing agents co-entrapped in these nanocarriers seems beneficial for cancer treatment. In the present study, multifunctional smart alginate/perfluorohexane nanodroplets were developed for co-delivery of doxorubicin and curcumin (a strong chemosensitizer)...
February 2, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28229638/intranasal-insulin-treatment-improves-memory-and-learning-in-a-rat-amyloid-beta-model-of-alzheimer-s-disease
#2
S Farzampour, A Majdi, S Sadigh-Eteghad
Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ25-35 (10 nmol/2 µl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD...
September 2016: Physiol Int
https://www.readbyqxmd.com/read/28197291/postoperative-right-ventricular-failure-in-cardiac-surgery
#3
REVIEW
Victor H Nieto Estrada, Daniel L Molano Franco, Albert A Valencia Moreno, Jose A Rojas Gambasica, Cristian C Cortes Nunez
Two cases of patients that developed right ventricular failure (RVF) after cardiac valve surgery are presented with a narrative revision of the literature. RVF involves a great challenge due to the severity of this condition; it has a low incidence among non-congenital cardiac surgery patients, is more likely associated with cardiovascular and pulmonary complications related to cardiopulmonary bypass (CPB), and is a cause of acute graft failure and of a higher early mortality in cardiac transplant. The morphologic and hemodynamic characteristics of the right ventricle and some specific factors that breed pulmonary hypertension after cardiac surgery are in favor of the onset of RVF...
December 2016: Cardiology Research
https://www.readbyqxmd.com/read/28194628/association-between-ck-mb-area-under-the-curve-and-tranexamic-acid-utilization-in-patients-undergoing-coronary-artery-bypass-surgery
#4
Sean van Diepen, Peter D Merrill, Michel Carrier, Jean-Claude Tardif, Mihai Podgoreanu, John H Alexander, Renato D Lopes
Myonecrosis after coronary artery bypass graft (CABG) surgery is associated with excess mortality. Tranexamic acid (TA), an anti-fibrinolytic agent, has been shown to reduce peri-operative blood loss without increasing the risk of myocardial infarction (MI); however, no large study has examined the association between TA treatment and post-CABG myonecrosis. In the MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II trial, inverse probability weighting of the propensity to receive TA was used to test for differences among the 656 patients receiving and 770 patients not receiving TA...
February 14, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28178660/plk1-inhibition-enhances-temozolomide-efficacy-in-idh1-mutant-gliomas
#5
Robert F Koncar, Zhengtao Chu, Lindsey E Romick-Rosendale, Susanne I Wells, Timothy A Chan, Xiaoyang Qi, El Mustapha Bahassi
Despite multimodal therapy with radiation and the DNA alkylating agent temozolomide (TMZ), malignant gliomas remain incurable. Up to 90% of grades II-III gliomas contain a single mutant isocitrate dehydrogenase 1 (IDH1) allele. IDH1 mutant-mediated transformation is associated with TMZ resistance; however, there is no clinically available means of sensitizing IDH1 mutant tumors to TMZ. In this study we sought to identify a targetable mechanism of TMZ resistance in IDH1 mutant tumors to enhance TMZ efficacy...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28164089/met-hgf-pathway-activation-as-a-paradigm-of-resistance-to-targeted-therapies
#6
REVIEW
Brian Ko, Tianfang He, Shirish Gadgeel, Balazs Halmos
Resistance to targeted therapeutics is a key issue limiting the long-term utility of these medications in the management of molecularly selected subsets of cancer patients, including patients with non-small cell lung cancer harboring oncogenic alterations affecting EGFR, ALK and other genes. Bypass resistance mediated by activation of MET kinase has emerged as a frequent, validated and pivotal resistance mechanism in multiple types of cancers. Biochemical understanding is accumulating to explain the unique role of MET in such bypass pathways, providing alternate downstream activation opportunities and intricate interactions during epithelial-mesenchymal transitions...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28159767/ticagrelor-reversal-in-vitro-assessment-of-four-haemostatic-agents
#7
Leyla Calmette, Anne-Céline Martin, Bernard Le Bonniec, Diane Zlotnik, Isabelle Gouin-Thibault, Christilla Bachelot-Loza, Pascale Gaussem, Anne Godier
AIM: Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate in vitro the efficacy of four haemostatic drugs (HDs), namely recombinant activated factor VII (rFVIIa), fibrinogen concentrate (Fib), tranexamic acid (TXA) and factor XIII concentrate (FXIII) to improve the haemostatic capacity in the presence of ticagrelor. METHODS: Blood was spiked with ticagrelor then supplemented by either HD or control...
February 3, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28156169/nanotransfersomes-loaded-thermosensitive-in-situ-gel-as-a-rectal-delivery-system-of-tizanidine-hcl-preparation-in-vitro-and-in-vivo-performance
#8
Fatma A Moawad, Adel A Ali, Heba F Salem
The purpose of the current study was to develop tizanidine HCl (TIZ; a myotonolytic agent used for treatment of spasticity) loaded nanotransfersomes intended for rectal administration, aiming to bypass the hepatic first-pass metabolism. TIZ-loaded nanotransfersomes were prepared by thin-film hydration method followed by characterization for various parameters including entrapment efficiency, vesicle diameter, in vitro release and ex vivo permeation studies. Transfersomal formulation composed of phosphatidylcholine and Tween 80 at a weight ratio of (85:15) gave a satisfactory results...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28155594/pbpk-modeling-a-predictive-eco-friendly-bio-waiver-tool-for-drug-research
#9
Baishakhi De, Koushik Bhandari, Ranjan Mukherjee, Prakash Katakam, Shanta K Adiki, Rohit Gundamaraju, Analava Mitra
BACKGROUND: The world has witnessed growing complexities in disease scenario influenced by the drastic changes in host-pathogen- environment triadic relation. Pharmaceutical R&Ds are in constant search of novel therapeutic entities to hasten transition of drug molecules from lab bench to patient bedside. Extensive animal studies and human pharmacokinetics are still the "gold standard" in investigational new drug research and bio-equivalency studies. Apart from cost, time and ethical issues on animal experimentation, burning questions arise relating to ecological disturbances, environmental hazards and biodiversity issues...
February 1, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28150393/acquired-hemophilia-a-manifesting-as-plasma-transfusion-uncontrolled-severe-bleeding-2-weeks-after-chorioamnionitis-induced-abortion
#10
Ayumi Matsuoka, Hiromasa Sasaki, Chiharu Sugimori, Shinya Hirabuki, Tsutomu Hoshiba, Hiroshi Fujiwara
Acquired hemophilia A (AHA) is a serious and rare complication of pregnancy, caused by autoantibodies to coagulation factor VIII after delivery. We here report the case of a 36-year-old primigravida woman who developed AHA following chorioamnionitis-caused miscarriage in the second trimester. Thirteen days after abortion, sudden, massive vaginal bleeding occurred with marked prolongation of activated partial thromboplastin time (APTT) in the absence of other abnormal coagulation data. Sequential transfusion of fresh frozen plasma did not achieve normalization of APTT...
February 2, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28124406/recombinant-porcine-factor-viii-for-high-risk-surgery-in-paediatric-congenital-haemophilia-a-with-high-titre-inhibitor
#11
S E Croteau, Y L Abajas, A S Wolberg, B I Nielsen, G R Marx, C W Baird, E J Neufeld, P E Monahan
INTRODUCTION: High-titre factor VIII (FVIII) inhibitors complicate peri-operative haemostasis. Recombinant porcine FVIII (r-pFVIII) may provide an alternative haemostatic agent for high-risk procedures and allow FVIII activity monitoring. AIM: Devise an effective haemostatic plan for repair of a progressively symptomatic aortic coarctation in a 5-year-old male with immune tolerance induction (ITI) refractory high-titre FVIII inhibitors. METHODS: Preprocedure human FVIII inhibitor titre was 58 Bethesda Units mL(-1) (BU) and cross-reacted to neutralize porcine FVIII at 30 BU...
January 25, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28122855/descendo-bifemoral-bypass-grafting-and-renal-artery-revascularization-to-treat-complex-obliterative-arteriopathy
#12
Stoyan Kondov, Bartosz Rylski, Fabian Alexander Kari, Rika Wobser, Simon Leschka, Matthias Siepe, Friedhelm Beyersdorf, Martin Czerny
OBJECTIVES: Our goal was to describe a new standardized approach in patients with extensive obliterative arteriopathy aimed at distal revascularization and surgical kidney recruitment via descendo-bifemoral bypass grafting and renal artery revascularization. METHODS: Three patients with Leriche's syndrome and either a compromised single kidney or unilateral significant renal artery stenosis were treated with a standardized surgical approach, restoration of distal perfusion via descendo-bifemoral bypass with synchronous (n = 2) left-sided renal artery revascularization or metachronous (n = 1) right-sided renal artery revascularization...
January 25, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28110808/suppression-of-graft-spasm-by-the-particulate-guanylyl-cyclase-activator-in-coronary-bypass-surgery
#13
Takeshi Kinoshita, Masashi Tawa, Tomoaki Suzuki, Yoshinari Aimi, Tohru Asai, Tomio Okamura
BACKGROUND: Spasm of arterial grafts is still a clinical problem in coronary artery bypass surgery. The present study was designed to examine the effect of particulate guanylyl cyclase activator (carperitide) as an antispastic agent in internal thoracic artery and gastroepiploic artery grafts. METHODS: Isolated arterial grafts taken during surgery were studied in organ bath in three ways: the relaxing effect of carperitide on vasoconstrictor-induced precontraction; the inhibitory effect of pretreatment with carperitide on subsequent vasoconstrictor-induced contraction; and the effect of carperitide and nitroglycerin on increase of intracellular cyclic guanosine monophosphate levels...
January 19, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28096836/coronary-artery-spasm-following-on-pump-coronary-artery-bypass-grafting-with-20-months-follow-up
#14
Adam R Kowalówka, Marcin Malinowski, Magdalena Onyszczuk, Marek Deja
We report on a 69-year-old woman who demonstrated native coronary artery and grafted vessel spasm following on-pump coronary artery bypass grafting (CABG). Despite intraaortic balloon pump (IABP) insertion, electrocardiogram (ECG) abnormalities did not disappear. Emergency coronary angiography (CAG) was performed. The patient was successfully treated with systemic and intracoronary injection of vasodilator agents. ECG changes disappeared, with normalized and stable hemodynamic function. Intraaortic balloon pump was maintained for 48 h...
December 2016: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
https://www.readbyqxmd.com/read/28079659/suspected-malignant-hyperthermia-in-the-setting-of-hypothermic-circulatory-arrest-for-type-a-aortic-dissection-repair-a-case-report
#15
Bryant Bunting, Joshua Knight, Stephen M McHugh
Malignant Hyperthermia (MH) is a life-threatening biochemical process of hypermetabolism brought about in susceptible individuals by a triggering drug or event. Type A aortic dissections are surgical emergencies requiring cardiopulmonary bypass and frequently deep hypothermic circulatory arrest. We present a case of suspected MH in a patient undergoing emergent repair of a type A aortic dissection. Upon arrival at our institution, the patient had multiple signs of MH. However, no known triggering agent had been administered...
January 11, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28079537/successful-total-hip-replacement-with-sequential-administration-of-bypassing-agents-in-an-adolescent-boy-with-hemophilia-a-and-high-inhibitor-titers
#16
Zühre Kaya, Özlem Orhan, Sacit Turanl, İdil Yenicesu, Ülker Koçak, Türkiz Gürsel
There are only a few reports of total hip replacement in patients with hemophilia A and inhibitors. We performed total hip replacement in an 18-year-old adolescent boy who had high inhibitor titers since infancy. Recombinant factor VIIa (NovoSeven) was used as a bypass agent during the surgery. There was no excessive introperative bleeding; however, postsurgical bleeding occurred and was controlled by sequential administration of recombinant factor VIIa and activated prothrombin complex concentrate (FEIBA)...
January 12, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28055186/antimicrobials-inspired-by-nonribosomal-peptide-synthetase-gene-clusters
#17
Xavier Vila-Farres, John Chu, Daigo Inoyama, Melinda A Ternei, Christophe Lemetre, Louis J Cohen, Wooyoung Cho, Boojala Vijay B Reddy, Henry A Zebroski, Joel S Freundlich, David S Perlin, Sean F Brady
Bacterial culture broth extracts have been the starting point for the development of numerous therapeutics. However, only a small fraction of bacterial biosynthetic diversity is accessible using this strategy. Here, we apply a discovery approach that bypasses the culturing step entirely by bioinformatically predicting small molecule structures from the primary sequences of the biosynthetic gene clusters. These structures are then chemically synthesized to give synthetic-bioinformatic natural products (syn-BNPs)...
February 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28054318/treating-patients-with-alk-rearranged-non-small-cell-lung-cancer-mechanisms-of-resistance-and-strategies-to-overcome-it
#18
REVIEW
M Drizou, E A Kotteas, N Syrigos
Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases...
January 4, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28038979/preclinical-evaluation-of-met-inhibitor-inc-280-with-or-without-the-epidermal-growth-factor-receptor-inhibitor-erlotinib-in-non-small-cell-lung-cancer
#19
Matthew S Lara, William S Holland, Danielle Chinn, Rebekah A Burich, Primo N Lara, David R Gandara, Karen Kelly, Philip C Mack
BACKGROUND: Although the epidermal growth factor receptor (EGFR) inhibitor erlotinib is initially effective in non-small-cell lung cancer (NSCLC) patients with tumors harboring activating mutations of EGFR, most subsequently develop acquired resistance. One recognized resistance mechanism occurs through activation of bypass signaling via the hepatocyte growth factor (HGF)-MET pathway. INC-280 is a small molecule kinase inhibitor of MET. We sought to demonstrate the activity of INC-280 on select NSCLC cell lines both as a single agent and in combination with erlotinib using exogenous HGF to simulate MET up-regulation...
November 21, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28034787/combination-of-nitric-oxide-and-drug-delivery-systems-tools-for-overcoming-drug-resistance-in-chemotherapy
#20
Jihoon Kim, Bryant C Yung, Won Jong Kim, Xiaoyuan Chen
Chemotherapeutic drugs have made significant contributions to anticancer therapy, along with other therapeutic methods including surgery and radiotherapy over the past century. However, multidrug resistance (MDR) of cancer cells has remained as a significant obstacle in the achievement of efficient chemotherapy. Recently, there has been increasing evidence for the potential function of nitric oxide (NO) to overcome MDR. NO is an endogenous and biocompatible molecule, contrasting with other potentially toxic chemosensitizing agents that reverse MDR effects, which has raised expectations in the development of efficient therapeutics with low side effects...
December 26, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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