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https://www.readbyqxmd.com/read/30120647/an-evaluation-of-risk-factors-to-predict-target-concentration-non-attainment-in-critically-ill-patients-prior-to-empiric-%C3%AE-lactam-therapy
#1
Sahand Imani, Hergen Buscher, Richard Day, Sheridan Gentili, Graham R D Jones, Debbie Marriott, Ross Norris, Indy Sandaradura
To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT)...
August 17, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/30120629/modified-fe-3-o-4-magnetic-nanoparticle-delivery-of-cpg-inhibits-tumor-growth-and-spontaneous-pulmonary-metastases-to-enhance-immunotherapy
#2
Xueyan Zhang, Fengbo Wu, Ke Men, Rong Huang, Bailin Zhou, Rui Zhang, Rui Zou, Li Yang
As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3 O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG...
August 17, 2018: Nanoscale Research Letters
https://www.readbyqxmd.com/read/30120418/cholinergic-regulation-of-mood-from-basic-and-clinical-studies-to-emerging-therapeutics
#3
REVIEW
Stephanie C Dulawa, David S Janowsky
Mood disorders are highly prevalent and are the leading cause of disability worldwide. The neurobiological mechanisms underlying depression remain poorly understood, although theories regarding dysfunction within various neurotransmitter systems have been postulated. Over 50 years ago, clinical studies suggested that increases in central acetylcholine could lead to depressed mood. Evidence has continued to accumulate suggesting that the cholinergic system has a important role in mood regulation. In particular, the finding that the antimuscarinic agent, scopolamine, exerts fast-onset and sustained antidepressant effects in depressed humans has led to a renewal of interest in the cholinergic system as an important player in the neurochemistry of major depression and bipolar disorder...
August 17, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/30120332/expression-profiling-in-a-mammalian-host-reveals-the-strong-induction-of-genes-encoding-lysm-domain-containing-proteins-in-enterococcus-faecium
#4
Margherita Cacaci, Caroline Giraud, Loic Leger, Riccardo Torelli, Cecilia Martini, Brunella Posteraro, Valentina Palmieri, Maurizio Sanguinetti, Francesca Bugli, Axel Hartke
Enterococcus faecium is an important health care-associated pathogen that is difficult to treat due to the high level of antibiotic resistance of clinical isolates. The identification of new potential therapeutic targets or vaccination strategies is therefore urgently needed. In this regard, we carried out a transcriptomic analysis of the E. faecium vancomycin-resistant strain AUS0004, comparing the gene expression of bacteria grown under laboratory conditions and bacteria isolated from an infection site. This analysis highlighted more than 360 genes potentially induced under infection conditions...
August 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30120227/z-fl-cocho-a-cathepsin-s-inhibitor-enhances-oxaliplatin-mediated-apoptosis-through-the-induction-of-endoplasmic-reticulum-stress
#5
Seung Un Seo, Kyoung-Jin Min, Seon Min Woo, Taeg Kyu Kwon
Multiple cancer cells highly express cathepsin S, which has pro-tumoral effects. However, it was previously unknown whether knockdown or a pharmacological inhibitor (ZFL) of cathepsin S acts as an inducer of ER stress. Here, ZFL and knockdown of cathepsin S markedly induced ER stress through the up-regulation of calcium levels in the cytosol. Induction of calcium levels by inhibition of cathepsin S is markedly blocked by an inhibitor of the IP3 receptor and the ryanodine receptor Ca2+ channel in the ER, but an inhibitor of a mitochondrial Ca2+ uniporter had no effect on ZFL-induced calcium levels...
August 17, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/30119985/managing-nonmetastatic-castration-resistant-prostate-cancer
#6
REVIEW
Joaquin Mateo, Karim Fizazi, Silke Gillessen, Axel Heidenreich, Raquel Perez-Lopez, Wim J G Oyen, Neal Shore, Matthew Smith, Christopher Sweeney, Bertrand Tombal, Scott A Tomlins, Johann S de Bono
CONTEXT: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation. OBJECTIVE: To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients...
August 14, 2018: European Urology
https://www.readbyqxmd.com/read/30119963/polyphyllin-i-inhibits-growth-and-invasion-of-cisplatin-resistant-gastric-cancer-cells-by-partially-inhibiting-cip2a-pp2a-akt-signaling-axis
#7
Yunfei Zhang, Ping Huang, Xuewen Liu, Yuchen Xiang, Te Zhang, Yezi Wu, Jiaxin Xu, Zhiting Sun, Weiguo Zhen, Liang Zhang, Yuan Si, Ying Liu
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties...
July 26, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/30119719/genetic-therapies-for-inherited-neuromuscular-disorders
#8
REVIEW
Mariacristina Scoto, Richard Finkel, Eugenio Mercuri, Francesco Muntoni
Inherited neuromuscular disorders encompass a broad group of genetic conditions, and the discovery of these underlying genes has expanded greatly in the past three decades. The discovery of such genes has enabled more precise diagnosis of these disorders and the development of specific therapeutic approaches that target the genetic basis and pathophysiological pathways. Such translational research has led to the approval of two genetic therapies by the US Food and Drug Administration: eteplirsen for Duchenne muscular dystrophy and nusinersen for spinal muscular atrophy, which are both antisense oligonucleotides that modify pre-mRNA splicing...
August 2018: Lancet Child & Adolescent Health
https://www.readbyqxmd.com/read/30119256/synergy-of-theophylline-reduces-necrotic-effect-of-berberine-induces-cell-cycle-arrest-and-parp-hmgb1-bcl-2-family-mediated-apoptosis-in-mda-mb-231-breast-cancer-cells
#9
Fatemeh Hashemi-Niasari, Azra Rabbani-Chadegani, Mahdieh Razmi, Soudabeh Fallah
Berberine, is a plant alkaloid, proved to have anticancer effect on various cancers. Theophylline (TH), a natural product, is widely used in the treatment of respiratory difficulties. The present study designed to elucidate the effects of theophylline and berberine combination on breast cancer cells cytotoxicity, gene expression and cell cycle. MTT assay revealed that berberine inhibited MDA-MB-231 breast cancer cells viability in a time and dose dependent manner (IC50 of 100 μM) but theophylline had no considerably effect on the cells...
July 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119199/the-mechanistic-insight-of-polyphenols-in-calcium-oxalate-urolithiasis-mitigation
#10
REVIEW
Salman Ahmed, Muhammad Mohtasheemul Hasan, Haroon Khan, Zafar Alam Mahmood, Seema Patel
About 12% of world population is affected by different forms of urolithiasis of which the recurrence rate in female is 47-60% and in male is 70-80%. Standard therapeutic agents (allopurinol, citrate, cystone and thiazide diuretics) are used to prevent and treat urolithiasis but these are not universally-effective due to common kidney stone relapse and other side effects. Surgical treatment causes long-term renal damage, hypertension and stone recurrence. Polyphenols, the plant-derived bioactive molecules, have showed protection against cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases, among a number of other ailments...
July 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119198/emerging-novel-drug-delivery-strategies-for-bioactive-flavonol-fisetin-in-biomedicine
#11
REVIEW
Piyush Mehta, Atmaram Pawar, Kakasaheb Mahadik, C Bothiraja
Fisetin (FIS), a bioactive flavonol found in the smoke tree (Cotinus coggygria), vegetables, fruits and nuts. It exhibits various therapeutic activities such as anti-oxidant, anti-inflammatory, anti-invasive, anti-tumorigenic, anti-angiogenic, anti-diabetic, cardioprotective and neuroprotective activities. In spite of the ever rising support for therapeutic activities, its clinical application is mainly limited because of poor water solubility, high lipophilicity and low oral bioavailability. Till date, numerous efforts have been made to surpass these limitations with the development of new improved delivery platforms...
July 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119188/antioxidant-and-apoptotic-effects-of-callistemon-lanceolatus-leaves-and-their-compounds-against-human-cancer-cells
#12
Kamal Ahmad, Zubair Bin Hafeez, Abdul Roof Bhat, Moshahid Alam Rizvi, Sonu C Thakur, Amir Azam, Fareeda Athar
Callistemon lanceolatus (Myrtaceae) has been utilized in folk medicine and its pharmacological properties are widely studied. Phytochemicals are effectively recognized as bases of pharmacologically potent drugs for the development of anticancer therapeutics. The free radical scavenging potential of numerous extracts of C. lanceolatus leaves, Hexane leaf extract (HLE), Chloroform leaf extract (CLE), Ethyl acetate leaf extract (ELE), Methanol leaf extract (MLE), and Aqueous leaf extract (ALE)) were determined by Biochemical assay...
July 18, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119174/novel-steroid-derivatives-synthesis-antileishmanial-activity-mechanism-of-action-and-in-silico-physicochemical-and-pharmacokinetics-studies
#13
Juliana da Trindade Granato, Juliana Alves Dos Santos, Stephane Lima Calixto, Natália Prado da Silva, Jefferson da Silva Martins, Adilson David da Silva, Elaine Soares Coimbra
The search for new drugs for the treatment of leishmaniasis is an important strategy for improving the current therapeutic arsenal for the disease. There are several limitations to the available drugs including high toxicity, low efficacy, prolonged parenteral administration, and high costs. Steroids are a diverse group of compounds with various applications in pharmacology. However, the antileishmanial activity of this class of molecules has not yet been explored. Therefore, in the present study, we investigated the antileishmanial activity and cytotoxicity of novel steroids against murine macrophages with a focus on the derivatives of cholesterol (CD), cholic acid (CA), and deoxycholic acid (DA)...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30119131/plumbagin-inhibits-the-proliferation-of-nasopharyngeal-carcinoma-6-10b-cells-by-upregulation-of-reactive-oxygen-species
#14
Baisen Li, Xiuhui Gu, Mingbo Wu, Ye Zhao, Jie Yang, Li Feng, Junjie Gou, Linyi Chen, Ting Li, Linpeng Li, Lan Wang, Li Zhu, Kun Zhang
Plumbagin (PLB) is the primary component of the traditional Chinese medicine Baihua Dan, and possesses anti-infection and anticancer effects, with the ability to enhance the sensitivity of tumor cells to radiation therapy. However, the anticancer effect of PLB on nasopharyngeal carcinoma and the underlying mechanisms remain unclear. In this study, we investigated the anticancer effects of PLB on nasopharyngeal carcinoma 6-10B cells and clarified its molecular mechanisms in vitro. The results showed that PLB was effective against 6-10B cells proliferation in a dose-dependent manner by inducing G2/M phase cell cycle arrest...
June 29, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/30118964/apremilast-prevent-doxorubicin-induced-apoptosis-and-inflammation-in-heart-through-inhibition-of-oxidative-stress-mediated-activation-of-nf-%C3%AE%C2%BAb-signaling-pathways
#15
Faisal Imam, Naif O Al-Harbi, Mohammad Matar Al-Harbi, Mushtaq Ahmad Ansari, Abdullah F Al-Asmari, Mohd Nazam Ansari, Wael A Al-Anazi, Saleh Bahashwan, Mashal M Almutairi, Musaad Alshammari, Mohammad Rashid Khan, Abdulaziz Mohammed Alsaad, Moureq Rashed Alotaibi
BACKGROUND: Doxorubicin is an effective, potent and commonly used anthracycline-related anticancer drug; however, cardiotoxicity compromises its therapeutic potential. Apremilast, a novel phosphodiesterase type 4-inhibitor, reported to have anti-inflammatory effects and modulating many inflammatory mediators. METHODS: The present study investigated the influence of apremilast against doxorubicin-induced cardiotoxicity in male Wistar rats. A total, 24 animals were divided into four groups of six animal each...
March 29, 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/30118931/does-emergent-implantation-of-a-vagal-nerve-stimulator-stop-refractory-status-epilepticus-in-children
#16
Daniele Grioni, Andrea Landi, Leonardo Fiori, Erik Pietro Sganzerla
PURPOSE: Status Epilepticus can be a serious life threatening event in epileptic patients. The definition of refractory or super-refractory Status Epilepticus was based on the therapeutic response to anti-epileptic and anesthetic drugs. Vagal Nerve Stimulation showed efficacy in treating drug-resistant epilepsy but there are only few reports on emergentplacement of Vagal Nerve Stimulator for refractory or super-refractory Status Epilepticus. METHODS: Among 49 children implanted at our Institution with Vagal Nerve Stimulation for drug-resistant epilepsy, the authors retrospectively identified those implanted for refractory or super-refractory Status Epilepticus, according with the current definitions...
August 11, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/30118848/two-novel-camptothecin-derivatives-inhibit-colorectal-cancer-proliferation-via-induction-of-cell-cycle-arrest-and-apoptosis-in-vitro-and-in-vivo
#17
Hongzhi Du, Yue Huang, Xiaoying Hou, Xingping Quan, Jingwei Jiang, Xiaohui Wei, Yang Liu, Hongyang Li, Puhai Wang, Meixiao Zhan, Xun Ai, Ligong Lu, Shengtao Yuan, Li Sun
At present, chemotherapy is still to be the preferred and most significant therapeutic strategy for cancer patients in clinical practice. Although Camptothecin (CPT) has been discovered for over half century, a series of CPT derivatives such as Topotecan (TPT) and irinotecan (CPT-11) have been approved and are still to be the first-line medicines for clinical application. Up to now, the topoisomerase 1 inhibitor continues to be a significant drug development research field. Based on previous study of the structure-activity relationship, we consider that the introduction of lipophilic group at C7 position can prolong the retention time and the hydroxyl esterification at C20 can eliminate the hydrogen bond interaction, stabilize the E-lactone form and promote the anti-cancer effect...
August 14, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30118832/polymeric-nanocapsules-as-drug-carriers-for-sustained-anticancer-activity-of-calcitriol-in-breast-cancer-cells
#18
Sabrina Nicolas, Marie-Alexandrine Bolzinger, Lars Petter Jordheim, Yves Chevalier, Hatem Fessi, Eyad Almouazen
Clinical use of calcitriol (1,25-dihydroxyvitamin D3 ) as an anticancer agent is currently limited by the requirement of supraphysiological doses and associated hypercalcemia. Nanoencapsulation of calcitriol is a strategy to overcome these drawbacks, allowing reduced administrated doses and/or frequency, while retaining the therapeutic activity towards cancer cells. For this purpose, we investigated the impact of calcitriol encapsulation on its antiproliferative activity and optimized formulation parameters with that respect...
August 14, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/30118774/neuroprotective-effects-of-bergenin-in-alzheimer-s-disease-investigation-through-molecular-docking-in-vitro-and-in-vivo-studies
#19
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/30118674/beta-lactam-carryover-in-arterial-and-central-venous-catheters-is-negligible
#20
Emily Marsh, Sylvia M Verhoven, Joseph J Groszek, William H Fissell, Guohua An, Pratish Patel, Buddy Creech, Matthew Shotwell
BACKGROUND: Therapeutic drug monitoring is used for aminoglycosides and vancomycin, and has been proposed for β-lactam antibiotics. Clinical blood samples in the ICU are often obtained via an existing vascular catheter rather than fresh needle phlebotomy. If antibiotics had previously been infused through a vascular catheter then used for blood sampling, carryover of antibiotic from the infusion to the sample might result in misleading assessments of target attainment. To address this concern we conducted a series of in vitro measurements of carryover for three commonly used antibiotics...
August 14, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
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