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https://www.readbyqxmd.com/read/28823085/chromaffin-cells-as-a-model-to-evaluate-mechanisms-of-cell-death-and-neuroprotective-compounds
#1
REVIEW
Cristobal de Los Rios, Maria F Cano-Abad, Mercedes Villarroya, Manuela G López
In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs...
August 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28822705/anti-dermatophyte-activity-of-leguminosae-plants-from-southern-brazil-with-emphasis-on-mimosa-pigra-leguminosae
#2
C B de Morais, M Scopel, G P R Pedrazza, F K da Silva, D F Dalla Lana, M L Tonello, S T S Miotto, M M Machado, L F S De Oliveira, A M Fuentefria, J A S Zuanazzi
BACKGROUND: Intensive prophylactic use of antifungals leads to the increase of drug resistance and the need for new and more effective treatments are real. Plants from Leguminosae family are rich in flavonoids, for which numerous biological activities have been described, including antifungal effects. PURPOSE: To screen methanolic extracts from Leguminosae species looking for alternative sources for antifungal agents (anti-dermatophyte and anti-Candida) and their innocuity...
August 16, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28822347/screening-and-confirmation-of-steroids-and-nitroimidazoles-in-urine-blood-and-food-matrices-sample-preparation-methods-and-liquid-chromatography-tandem-mass-spectrometric-separations
#3
Ádám Tölgyesi, Enikő Barta, Andrea Simon, Thomas J McDonald, Virender K Sharma
Veterinary drugs containing synthetic anabolic steroid and nitroimidazole active agents are not allowed for their applications in livestock of the European Union (EU). This paper presents analyses of twelve selected steroids and six nitroimidazole antibiotics at low levels (1.56μg/L-4.95μg/L and 0.17μg/kg-2.14μg/kg, respectively) in body fluids and egg incurred samples. Analyses involved clean-up procedures, high performance liquid chromatography (HPLC) separation, and tandem mass spectrometric screening and confirmatory methods...
August 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28822201/-pharmacokinetic-research-strategies-of-compatibilities-and-synergistic-effects-of-classical-danshen-herb-pairs-based-on-pharmacokinetics-of-danshen-bingpian-and-danshen-honghua
#4
Cui-Ying Zhang, Wei-Guang Ren
Herb pairs are usual clinical compatibility forms and one of compound prescription sources in Chinese medicine. Pharmacokinetic research in vivo is one of the important items in elucidating the mechanism for synergistic and attenuated mechanisms of herb pairs. The paper comprehensively summarized and systemized the pharmacokinetic researches of marker-ingredients about Danshen-Honghua and Danshen-Bingpian in order to elucidate the rationality and scientificity of herb pairs and provide some feasible suggestions on the pharmacokinetics of drugs in the future...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28822107/successful-treatment-and-fdg-pet-ct-monitoring-of-hhv-6-encephalitis-in-a-non-neutropenic-patient-case-report-and-literature-review
#5
Elda Righi, Alessia Carnelutti, Daniele Muser, Francesco Zaja, Elisa Lucchini, Federico Pea, Fernando Di Gregorio, Abass Alavi, Matteo Bassetti
Human herpesvirus (HHV)-6 reactivation is associated with severe forms of encephalitis among patients undergoing hematopoietic stem cell transplantation. Cases in non-neutropenic patients are uncommon. The efficacy of ganciclovir and other compounds that are used for the treatment of HHV-6 encephalitis remains suboptimal and linked to toxicity. Valganciclovir, the oral prodrug of ganciclovir, could be practical to treat outpatients, but it is not commonly used for severe cases. We report a case of HHV-6 encephalitis in a non-neutropenic patient successfully treated with valganciclovir and undergoing therapeutic drug monitoring in plasma and in the cerebrospinal fluid...
August 18, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#6
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28822019/gypenoside-ix-suppresses-p38-mapk-akt-nf%C3%AE%C2%BAb-signaling-pathway-activation-and-inflammatory-responses-in-astrocytes-stimulated-by-proinflammatory-mediators
#7
Xiaoshuang Wang, Liu Yang, Li Yang, Faping Xing, Hua Yang, Liyue Qin, Yunyi Lan, Hui Wu, Beibei Zhang, Hailian Shi, Cheng Lu, Fei Huang, Xiaojun Wu, Zhengtao Wang
Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo...
August 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28821762/multi-tissue-interactions-in-an-integrated-three-tissue-organ-on-a-chip-platform
#8
Aleksander Skardal, Sean V Murphy, Mahesh Devarasetty, Ivy Mead, Hyun-Wook Kang, Young-Joon Seol, Yu Shrike Zhang, Su-Ryon Shin, Liang Zhao, Julio Aleman, Adam R Hall, Thomas D Shupe, Andre Kleensang, Mehmet R Dokmeci, Sang Jin Lee, John D Jackson, James J Yoo, Thomas Hartung, Ali Khademhosseini, Shay Soker, Colin E Bishop, Anthony Atala
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#9
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#10
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821485/simple-evaluation-method-for-cyp3a4-induction-from-human-hepatocytes-the-relative-factor-approach-with-an-induction-detection-limit-concentration-based-on-the-emax-model
#11
Shino Kuramoto, Motohiro Kato, Hidetoshi Shindoh, Akihisa Kaneko, Masaki Ishigai, Seiji Miyauchi
We investigated the robustness and utility of the relative factor (RF) approach based on the Emax model, which was reported by Kaneko, using mRNA induction data of 10 typical CYP3A4 inducers in cryopreserved human hepatocytes. The RF value is designated as the ratio of the induction detection limit concentration (IDLC) for a standard inducer, such as rifampicin (RIF) or phenobarbital (PB), to that for the compound (RFRIF is IDLCRIF/IDLCcpd; RFPB is IDLCPB/IDLCcpd). An important feature of the RF approach is that the profiles of the induction response curves on the logarithmic scale remain unchanged irrespective of inducers but are shifted parallel depending on the EC50 values...
August 18, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28821396/the-new-hdac1-inhibitor-lg325-ameliorates-neuropathic-pain-in-a-mouse-model
#12
Maria Domenica Sanna, Luca Guandalini, Maria Novella Romanelli, Nicoletta Galeotti
Current analgesic therapies for treatment of neuropathic pain are unsatisfactory. Neuropathic pain is, therefore, undertreated and there is a significant need for a better pharmacotherapy. Increasing evidence indicate that histone deacetylation is a critical step in nerve injury pain. To obtain an innovative treatment for the management of neuropathic pain, we investigated the pharmacological effects produced by the new histone deacetylase (HDAC)-1 selective inhibitor, LG325, in a mouse model of trauma-induced peripheral mononeuropathy provoked by spared nerve injury (SNI)...
August 15, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28821394/activation-of-ampk-to-the-neuroprotection-in-the-oxidative-stress-by-advanced-glycosylation-end-products-in-human-neural-stem-cells
#13
Chien-Hung Lin, Yi-Chuan Cheng, Christopher J Nicol, Kuan-Hung Lin, Chia-Hui Yen, Ming-Chang Chiang
Advanced glycosylation end products (AGEs) formation is correlated with the pathogenesis of diabetic neuronal damage, but its links with oxidative stress are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). Once activated, AMPK regulates many pathways central to metabolism and energy balance including, glucose uptake, glycolysis and fatty acid oxidation. AMPK is also present in neurons, but its role remains unclear...
August 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28821164/cape-gooseberry-physalis-peruviana-juice-as-a-modulator-agent-for-hepatocellular-carcinoma-linked-apoptosis-and-cell-cycle-arrest
#14
Hanaa A Hassan, Hanaa M Serag, Makwan S Qadir, Mohamed Fawzy Ramadan
BACKGROUND: Cape gooseberry (Physalis peruviana) fruit is highly nutritious with high content of health-promoting compounds including minerals, phenolic compounds, as well as vitamins A and C. Physalis peruviana fruits were used as mutagenic, antispasmodic, anticoagulant, and antileucemis agents. OBJECTIVE: The objective of the present work was to study the role of cape gooseberry juice (CG) as a natural modulator agent for adverse aspects associated with hepatocellular carcinoma (HCC)...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28821095/an-o-acetyl-glucomannan-from-the-rhizomes-of-curculigo-orchioides-structural-characterization-and-anti-osteoporosis-activity-in-vitro
#15
Xueqian Wang, Mengliu Zhang, Dawei Zhang, Shumei Wang, Chunyan Yan
Osteoporosis is characterized by a reduction in bone mass and bone mineral density, which weakens the bone. Due to the side effects associated with drugs that are currently used to treat this disease, an increasing number of studies have focused on the research of effective ingredients derived from natural products. In particular, polysaccharides extracted from Chinese herbal medicines have received increasing attention. In this study, we isolated a homogeneous polysaccharide (COP90-1) from the dried rhizomes of Curculigo orchioides, a famous traditional Chinese medicine that is widely used in China, and determined its structure using the combined methods of chemical and spectral analyses...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28821069/preparation-and-pharmacological-evaluation-of-norcantharidin-conjugated-carboxymethyl-chitosan-in-mice-bearing-hepatocellular-carcinoma
#16
Zhiwen Jiang, Jinhua Chi, Baoqin Han, Wanshun Liu
In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28821011/the-photodynamic-action-of-pheophorbide-a-induces-cell-death-through-oxidative-stress-in-leishmania-amazonensis
#17
Nathielle Miranda, Hélito Volpato, Jean Henrique da Silva Rodrigues, Wilker Caetano, Tânia Ueda-Nakamura, Sueli de Oliveira Silva, Celso Vataru Nakamura
Leishmaniasis is a disease caused by hemoflagellate protozoa, affecting millions of people worldwide. The difficulties of treating patients with this parasitosis include the limited efficacy and many side effects of the currently available drugs. Therefore, the search for new compounds with leishmanicidal action is necessary. Photodynamic therapy has been studied in the medical field because of its selectivity, utilizing a combination of visible light, a photosensitizer compound, and singlet oxygen to reach the area of treatment...
August 11, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28820965/systematic-identification-of-mcu-modulators-by-orthogonal-interspecies-chemical-screening
#18
Daniela M Arduino, Jennifer Wettmarshausen, Horia Vais, Paloma Navas-Navarro, Yiming Cheng, Anja Leimpek, Zhongming Ma, Alba Delrio-Lorenzo, Andrea Giordano, Cecilia Garcia-Perez, Guillaume Médard, Bernhard Kuster, Javier García-Sancho, Dejana Mokranjac, J Kevin Foskett, M Teresa Alonso, Fabiana Perocchi
The mitochondrial calcium uniporter complex is essential for calcium (Ca(2+)) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca(2+) signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28820955/integration-of-an-in-situ-maldi-based-high-throughput-screening-process-a-case-study-with-receptor-tyrosine-kinase-c-met
#19
Katrin Beeman, Jens Baumgärtner, Manuel Laubenheimer, Karlheinz Hergesell, Martin Hoffmann, Ulrich Pehl, Frank Fischer, Jan-Carsten Pieck
Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated "in-line reader" for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components...
August 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28820953/a-fluorescence-based-high-throughput-assay-for-the-identification-of-anticancer-reagents-targeting-fructose-1-6-bisphosphate-aldolase
#20
Eun Jeong Cho, Ashwini K Devkota, Gabriel Stancu, Ramakrishna Edupunganti, Garth Powis, Kevin N Dalby
A high rate of glycolysis, which supplies energy and materials for anabolism, is observed in a wide range of tumor cells, making it a potential pathway to control cancer growth. ALDOA is a multifunctional enzyme in the glycolytic pathway and also promotes HIF-1α, which is of importance in hypoxic solid tumors. The current method for assaying ALDOA activity involves monitoring the consumption of NADH in vitro using absorbance or intrinsic fluorescence via a coupled enzymatic reaction. Here, we report the development of a homogeneous biochemical assay that can overcome limitations of current methods, in particular for the application of high-throughput drug screening...
August 1, 2017: SLAS Discovery
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