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https://www.readbyqxmd.com/read/29679881/ventrolateral-orbital-cortex-oxytocin-attenuates-neuropathic-pain-through-periaqueductal-gray-opioid-receptor
#1
Mina Taati, Esmaeal Tamaddonfard
BACKGROUND: Oxytocin plays an important role in supraspinal modulation of pain. In the present study, we investigated the effects of ventrolateral orbital cortex (VLOC) microinjection of oxytocin on neuropathic pain after blockade of opioid receptors in this area and ventrolateral periaqueductal gray (vlPAG). METHODS: Neuropathic pain was induced by complete transcection of preoneal and tibial branches of sciatic nerve. The VLOC and vlPAG were unilaterally (contralateral to the sciatic nerve-injured side) and bilaterally implanted with guide cannulas, respectively...
December 21, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29679812/protective-role-of-nimbolide-against-chemotherapeutic-drug-hydroxyurea-induced-genetic-and-oxidative-damage-in-an-animal-model
#2
Md Fahim Ahmad, Mohd Owais Ansari, Sana Jameel, Ab Latif Wani, Nuzhat Parveen, Hifzur R Siddique, G G H A Shadab
Nimbolide is known to be an antioxidant found in neem plant. Hydroxyurea is a medication frequently used in sickle-cell disease, different cancers and HIV infection. The present study aimed to evaluate the adverse effect of HU and possible amelioration by nimbolide in Wistar rats. To test our hypothesis, we performed genotoxicity tests, biochemical assays, and histopathological studies. We observed that HU caused higher levels of genotoxicity in the treated animals. The observed genetic and oxidative damage might be due to the presence of reactive species as HU increased the level of the malondialdehyde-a biomarker of oxidative damage...
April 12, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29679711/establishment-of-a-drug-induced-rhabdomyolysis-mouse-model-by-co-administration-of-ciprofloxacin-and-atorvastatin
#3
Akiko Matsubara, Shingo Oda, Sho Akai, Koichi Tsuneyama, Tsuyoshi Yokoi
Rhabdomyolysis is one of the serious side effects of ciprofloxacin (CPFX), a widely used antibacterial drug; and occasionally, acute kidney injury (AKI) occurs. Often, rhabdomyolysis has occurred in patients taking CPFX co-administered with statins. The purpose of this study is to establish a mouse model of drug-induced rhabdomyolysis by co-administration of CPFX and atorvastatin (ATV) and to clarify the mechanisms of its pathogenesis. C57BL/6J mice treated with L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor, were orally administered with CPFX and ATV for 4 days...
April 18, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29679677/use-of-toxicogenomics-in-drug-safety-evaluation-current-status-and-an-industry-perspective
#4
John L Vahle, Ulf Anderson, Eric A G Blomme, Jean-Christophe Hoflack, Daniel P Stiehl
Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time...
April 18, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29679667/systemic-delivery-of-bace1-sirna-through-neuron-targeted-nanocomplexes-for-treatment-of-alzheimer-s-disease
#5
Pengzhen Wang, Xiaoyao Zheng, Qian Guo, Peng Yang, Xiaoying Pang, Kang Qian, Wei Lu, Qizhi Zhang, Xinguo Jiang
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29679655/n-acetylcysteine-transforms-necrosis-into-apoptosis-and-affords-tailored-protection-from-cisplatin-cytotoxicity
#6
Sandra M Sancho-Martínez, Laura Prieto-García, Marta Prieto, Isabel Fuentes-Calvo, José M López-Novoa, Ana I Morales, Carlos Martínez-Salgado, Francisco J López-Hernández
Nephrotoxicity is the main limitation to the dosage and anticancer efficacy of cisplatin. Cisplatin produces tubular epithelial cell apoptosis and necrosis depending on the concentration of the drug. Protection from cisplatin nephrotoxicity must therefore tackle both cell death modes. For its ability to reduce cisplatin reactivity, in addition to its antioxidant effect, we tested and found that N-acetylcysteine (NAC) was most effective at inhibiting cisplatin cytotoxicity. NAC has no significant effect on cell death induced by either cycloheximide or Fas activation, indicating a rather selective action...
April 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29679654/the-vanillin-derivative-6-bromine-5-hydroxy-4-methoxybenzaldehyde-induces-aberrant-mitotic-progression-and-enhances-radio-sensitivity-accompanying-suppression-the-expression-of-plk1-in-esophageal-squamous-cell-carcinoma
#7
Meng-Meng Gu, Ming Li, Dexuan Gao, Lang-Huan Liu, Yue Lang, Si-Ming Yang, Hongling Ou, Bo Huang, Ping-Kun Zhou, Zeng-Fu Shang
Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase...
April 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29679641/ethanol-induced-cardiomyocyte-toxicity-involves-autophagy-nfkb-transcription-factor
#8
Jessica Maiuolo, Alessia Maretta, Micaela Gliozzi, Vincenzo Musolino, Cristina Carresi, Francesca Bosco, Rocco Mollace, Federica Scarano, Ernesto Palma, Miriam Scicchitano, Saverio Nucera, Domenico Sergi, Saverio Muscoli, Santo Gratteri, Carolina Muscoli, Vincenzo Mollace
Chronic ethanol (EtOH) consumption causes early detrimental consequences in many tissues including the myocardium, though the molecular mechanisms leading to the alcoholic cardiomyopathy (ACM) still remain to be elucidated. Here, we studied several biomolecular changes occurring in cardiomyoblasts after their exposure to sublethal concentrations of EtOH and the potential synergistic effect with methylmercury (MM) or doxorubicin (DOXO), which are known to produce direct myocardial dysfunction. In addition, the possible role of autophagic responses and Nuclear Factor kappa-B (NFkB) modulation in early post-alcoholic myocardial damage has been investigated...
April 18, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29679571/metformin-ameliorates-tgf-%C3%AE-1-induced-osteoblastic-differentiation-of-human-aortic-valve-interstitial-cells-by-inhibiting-%C3%AE-catenin-signaling
#9
Liu Fayuan, Chu Chong, Wei Qinyu, Shi Jiawei, Li Huadong, Dong Nianguo
Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-β1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29679557/acetaminophen-induced-liver-injury-is-attenuated-in-transgenic-fat-1-mice-endogenously-synthesizing-long-chain-n-3-fatty-acids
#10
Ruibing Feng, Yang Wang, Conghui Liu, Chunyan Yan, Hang Zhang, Huanxing Su, Jing X Kang, Chang-Zhen Shang, Jian-Bo Wan
Acetaminophen (APAP) overdose-caused hepatotoxicity is the most commonly cause of drugs-induced liver failurecharacterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29679474/population-pharmacokinetics-of-gliclazide-in-normal-and-diabetic-rabbits
#11
Mastan Shaik, Shabana Shaik, Eswar Kumar Kilari
Gliclazide is a second-generation sulphonylurea drug widely used in the treatment of type 2 diabetes. However, there is no single report to describe the population pharmacokinetics of gliclazide in animal models. This study was aimed to evaluate the population pharmacokinetics (PK) of gliclazide in normal and alloxan-induced diabetic rabbits using nonlinear mixed effects modeling. A total of 90 New Zealand white rabbits were administered with 3 doses (4.13, 8.27 and 16.53 mg/kg b.wt) of gliclazide by an oral route...
April 21, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29679296/methylmercury-reduces-synaptic-transmission-and-neuronal-excitability-in-rat-hippocampal-slices
#12
J Gutiérrez, A M Baraibar, E Albiñana, P Velasco, J M Solís, J M Hernández-Guijo
In a previous study, we pointed out that the neurotoxic action evoked by methylmercury (MeHg), a potent environmental pollutant responsible for fatal food poisoning, is associated with alterations of cellular excitability by irreversible blockade of sodium and calcium currents. Here, we investigated the MeHg effects on synaptic transmission and neuronal plasticity using extracellular field recording in CA1 area of rat hippocampal slices. MeHg caused a fast and drastic depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner with an IC50 of 25...
April 21, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29679289/cross-state-dependency-of-learning-between-tramadol-and-mk-801-in-the-mouse-dorsal-hippocampus-involvement-of-nitric-oxide-no-signaling-pathway
#13
Majid Jafari-Sabet, Shiva Amiri, Ramin Ataee
RATIONALE: Tramadol, an atypical μ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al...
April 21, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29679288/calcium-chloride-mimics-the-effects-of-acamprosate-on-cognitive-deficits-in-chronic-alcohol-exposed-mice
#14
Grishma Pradhan, Patrick R Melugin, Fei Wu, Hannah M Fang, Rachel Weber, Sven Kroener
RATIONALE: Acamprosate (calcium-bis N-acetylhomotaurinate) is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Acamprosate can improve executive functions that are impaired by chronic intermittent ethanol (CIE) exposure. Recent work has suggested that acamprosate's effects on relapse prevention are due to its calcium component, which raises the question whether its pro-cognitive effects are similarly mediated by calcium...
April 20, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29679139/reality-of-the-emetogenic-level-of-irinotecan
#15
Maria-Angeles Garcia-Del-Barrio, Salvador Martin-Algarra, Azucena Aldaz Pastor
PURPOSE: To assess the emetogenic potential of different chemotherapy (CT) regimens in daily clinical practice in an outpatient setting. To optimize antiemetic prophylaxis if necessary METHODS: Prospective and retrospective review of the emetogenic potential of CT regimens used in adult patients in an outpatient setting RESULTS: We assess the chemotherapy-induced nausea and vomiting (CINV) of 50 different CT regimens used on 157 different patients in an outpatient setting. We found that the CT usually classified as highly emetogenic, including cisplatin and anthracycline-cyclophosphamide combination, had the higher incidence of CINV (37...
April 21, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29679028/radiosensitization-by-marine-sponge-agelas-sp-extracts-in-hepatocellular-carcinoma-cells-with-autophagy-induction
#16
Changhoon Choi, Arang Son, Hyi-Seung Lee, Yeon-Ju Lee, Hee Chul Park
Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29679000/valsartan-alleviates-insulin-resistance-in-skeletal-muscle-of-chronic-renal-failure-rats
#17
Yang Wang, Ri-Bao Wei, Yue Yang, Ting-Yu Su, Meng-Jie Huang, Ping Li, Xiang-Mei Chen
BACKGROUND Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR...
April 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29678951/cyclooxygenase-1-and-2-play-contrasting-roles-in-listeria-stimulated-immunity
#18
Erin Theisen, Courtney E McDougal, Masako Nakanishi, David M Stevenson, Daniel Amador-Noguez, Daniel W Rosenberg, Laura J Knoll, John-Demian Sauer
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. NSAIDs are used following childhood vaccinations and cancer immunotherapies; however, how NSAIDs influence the development of immunity following these therapies is unknown. We hypothesized that NSAIDs would modulate the development of an immune response to Listeria monocytogenes -based immunotherapy. Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29678774/glial-cells-modulate-hippocampal-synaptic-plasticity-in-morphine-dependent-rats
#19
Azadeh Elahi-Mahani, Soomaayeh Heysieattalab, Narges Hosseinmardi, Mahyar Janahmadi, Fatemeh Sadat Seyedaghamiri, Habibeh Khoshbouei
Drugs of abuse mediate adaptive mechanisms leading to alterations in the synaptic plasticity that has been shown to underlie addictive behaviors. Glial cells play a critical role in modulation of synaptic strength and are potentially involved in drug addiction. Chronic administration of morphine has been shown to increase glial cell activation; therefore, it is possible that altered neuroplasticity induced by drugs of abuse is in part mediated by the activity of glial cells. We investigated the effect of hippocampal glial inhibition on synaptic plasticity in morphine treated rats...
April 17, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29678741/identification-and-characterization-of-an-endolysin-like-from-bacillus-subtilis
#20
Hossein Noormohammdi, Shamsozoha Abolmaali, Shakiba Darvish Alipour Astaneh
Drug-resistant Gram-positive pathogens have been a rising risk in hospitals and food industries from the last decades. Here in, the potential of endolysin production in Dasht Desert Bacterial Culture Collection (DDBCC), against indicator bacteria, was investigated. DDBCC was screened against autoclaved-indicator bacteria; Streptococcus faecalis, Streptococcus pyogenes, Bacillus sp, Bacillus subtilis and Staphylococcus aureus as the substrates for the endolysin enzymes. The endolysins were produced in BHI medium followed by ammonium sulfate purification...
April 17, 2018: Microbial Pathogenesis
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