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Clinical and Experimental Pharmacology & Physiology

Rehab M Badi, Dalia G Mostafa, Eman F Khaleel, Huda H Satti
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR). Resveratrol (RES) a potent hypolipidemic dietary polyphenol has been identified for its ability to prevent hepatic steatosis and hepatic IR in high-fat diet (HFD)-fed murine models of NAFLD. In the present study, we have carried an in vivo animal experiment to identify a novel mechanism for RES protective action. Sub-chronic (45 days) RES pre-treatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser307 ) and increasing p-IRS(Tyr612 ), p-Akt(Ser473 ) and p-GSK3(Ser9 )...
February 17, 2019: Clinical and Experimental Pharmacology & Physiology
G Kanigur Sultuybek, T Soydas, G Yenmis
Aging can be defined as the progressive failure of repair and maintenance systems with a consequent accumulation of cellular damage in nucleic acids, proteins, and lipids. These various types of damage promote aging by driving cellular senescence and apoptosis. NF-kB (nuclear factor-kappa B) pathway is one of the key mediators of aging and this pathway is activated by genotoxic, oxidative and inflammatory stress, and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, and inflammation...
February 12, 2019: Clinical and Experimental Pharmacology & Physiology
Keisuke Obara, Satoko Imanaka, Hiroka Fukuhara, Fumiko Yamaki, Kazuhiro Matsuo, Takashi Yoshio, Yoshio Tanaka
We investigated the potential augmenting effects of 19 clinically available antidepressants on noradrenaline (NA)-induced contractions in guinea pig urethra smooth muscle (USM). Concentration-response curves for NA-induced contractions in guinea pig USM strips were obtained in the absence or presence of selected antidepressants. Desipramine, an active metabolite of imipramine, produced a contraction and potentiated NA-induced contraction at the distal urethra without affecting the proximal urethra. Further, nortriptyline and amoxapine, tricyclic antidepressants, produced a contraction and potentiated NA-induced contraction at the distal urethra...
February 8, 2019: Clinical and Experimental Pharmacology & Physiology
Huda Mohammed Alkreathy, Mayson H Alkhatib, Safaa Ahmed Al Musaddi, Khadijah Saeed A Balamash, Nadia Nour Osman, Aftab Ahmad
Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improve the absorption and specificity of drugs towards tumor cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects...
February 6, 2019: Clinical and Experimental Pharmacology & Physiology
Meric A Altinoz, Aysel Ozpinar, Alp Ozpinar, Jennifer L Perez, İlhan Elmaci
Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as an urinary antiseptic. Methenamine is higly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. At acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine gained a renewal of interest due to antibiotic resistant bacteria urinary tract infections; interestingly, bacteria can not gain resistance to formaldehyde...
February 5, 2019: Clinical and Experimental Pharmacology & Physiology
Amol Sherikar, Rakesh Dhavale, Manish Bhatia
The main aim of this work is to find out novel chemical moieties with potent anti-inflammatory and vasorelaxant activities with reduced gastric toxicities. For fulfilling the above aim, here we investigated novel chalcones (1, 3-diphenylprop-2-en-1-one derivatives) with nitric oxide (NO) and hydrogen sulfide (H2 S) donating potency for anti-inflammatory activity by carrageenan-induced rat paw edema. These molecules then further evaluated for in-vitro NO-releasing potency and vasorelaxation effect on isolated adult goat aortic tissue...
February 3, 2019: Clinical and Experimental Pharmacology & Physiology
Chaoming He, Yanyan Sun, Bo Yan, Haiyun Chen, Yu Zheng, Ying Tang
We report a case of a 105-year-old woman who was treated with Alteplase for acute ischaemic stroke (AIS). On arrival, this centenarian Woman had sudden-onset aphasia and right-sided hemiparesis, her baseline National Institutes of Health Stroke Scale (NIHSS) score was 21. An acute noncontrast brain CT scan showed only mild white matter disease. After assessing the patient's risk-benefit ratio, the patient was administered intravenous Alteplase (0.9 mg/kg) 2.5 hours after symptom onset. Her right hemiparesis and aphasia eased within 24 hours after Alteplase treatment...
January 29, 2019: Clinical and Experimental Pharmacology & Physiology
Shuji Gamoh, Tatsuo Shiba, Donald J DiPette, Ryuichi Yamamoto
Many hypertensive animal models have been developed and used to elucidate the pathophysiology of hypertension and to develop antihypertensive drugs. Among them, the spontaneous hypertensive rat (SHR), deoxycorticosterone acetate (DOCA)-treated and high salt intake rat (DOCA-salt), and high sodium-fed Dahl salt-sensitive rat (HS) models are commonly used. Multiple studies have been conducted; however, elevation in blood pressure in these models due to the reactivity of adrenergic vasoconstriction has not been well characterized in a centralized experiment...
January 29, 2019: Clinical and Experimental Pharmacology & Physiology
Welder Zamoner, Iara Ranona Sousa Prado, André Luis Balbi, Daniela Ponce
Vancomycin is an antibiotic used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis may lead to multiple organ failure; it is considered a risk factor for the development of acute kidney injury (AKI), with an overall mortality rate of around 45%, which can reach the surprising rate of 70% with the combination of AKI and sepsis...
January 9, 2019: Clinical and Experimental Pharmacology & Physiology
Parvaneh Mohseni-Moghaddam, Seyed Shahabeddin Sadr, Mehrdad Roghani, Somayeh Arabzadeh, Safoura Khamse, Elham Zamani, Marjan Hosseini, Fatemeh Moradi
Temporal lobe epilepsy (TLE) is one of the most prevalent types of epilepsy in human. Huperzine A (Hup-A) has been reported to possess antioxidative and anti-inflammatory properties; however, its role in TLE induced by kainic acid has not been determined. The current study investigated the protective effects of Hup-A (0.1 mg/kg) in kainic acid-induced model of TLE in the rat. In our study, we found that Hup-A significantly prevented the seizure intensity and learning and memory deterioration which was assessed by Morris water maze (MWM) and novel object recognition task (NOR)...
January 8, 2019: Clinical and Experimental Pharmacology & Physiology
Kathryn S Clark, Claire Coleman, Rhiannon Shelton, Lydia A Heemstra, Colleen M Novak
Caffeine and its derivatives have been used, alone and in combination with other phytochemicals, as weight-loss supplements. Caffeine affects several physiological and behavioral aspects of energy balance, including increasing locomotor activity. Here, we investigate the potential for caffeine to enhance activity thermogenesis and energy expenditure (EE) even when activity level is held constant. To do this, EE and muscle thermogenesis were measured in rats during treadmill walking regimens, with and without caffeine (25 mg/kg, i...
January 8, 2019: Clinical and Experimental Pharmacology & Physiology
Yangui Wang, Cuizhong Liu, Xin He, Yingzhao Li, Yan Zou
Endothelial progenitor cells (EPCs) are critical for vascular regeneration and function, but are reduced in hypertensive disorders of pregnancy. We aimed to determine the possible effects of antihypertensive drugs, such as metoprolol, methyldopa, and nifedipine, on EPC number and functions in patients with gestational hypertension and preeclampsia. We collected blood samples from 30 normal pregnant women, 67 patients with gestational hypertension and 48 patients with preeclampsia. The patients received no drug or an antihypertensive drug, such as metoprolol, methyldopa, or nifedipine, between 20 to 24 weeks of gestation...
January 7, 2019: Clinical and Experimental Pharmacology & Physiology
Qian Wang, Meng-Fei Yu, Wen-Jing Zhang, Bei-Bei Liu, Qing-Yang Zhao, Xi Luo, Hao Xu, Yu-Shan She, Dun-An Zang, Jun-Ying Qiu, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Lu Xue, Weiwei Chen, Li-Qun Ma, Xiaowei Nie, Chenyou Shen, Shu Chen, Shanshan Chen, Quan Liu, Jiapei Dai, Gangjian Qin, Yun-Min Zheng, Yong-Xiao Wang, Ronghua ZhuGe, Jingyu Chen, Qing-Hua Liu
Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans...
January 4, 2019: Clinical and Experimental Pharmacology & Physiology
Aleksandra Suszka-Świtek, Artur Pałasz, Łukasz Filipczyk, Itiana Castro Menezes, Kinga Mordecka-Chamera, Tommaso Angelone, Katarzyna Bogus, Flora Bacopoulou, John J Worthington, Ryszard Wiaderkiewicz
The recently discovered peptide phoenixin (PNX) and its receptor GPR173 are novel factors that exhibit a large spectrum of regulatory activity, especially when considered as a central modulator of GnRH-related hormonal control of reproductive processes. It has been already proven that GnRH agonists and antagonists can modulate peptidergic signaling in the HPG axis. Despite these findings, there is so far no information regarding the influence of treatment with GnRH analogues on SMIM20/phoenixin signaling in the hypothalamic-pituitary-gonadal axis...
January 4, 2019: Clinical and Experimental Pharmacology & Physiology
Yang Yu, Leilei Wang, Man Gao, Hongbo Guan
Preeclampsia (PE) is a leading cause of maternal and perinatal death. Accumulated evidence suggests that many long non-coding RNAs (lncRNAs) abnormally expressed in placentas from PE patients, and they may play functional roles in the development of PE. The present study aimed to investigate the functional role TUG1 in PE and explore the potential molecular mechanisms. Clinically, the expression of TUG1 in placental tissues from PE and normal controls were determined. In vitro, human trophoblast HTR-8/SVneo and JAR cells were employed for loss or gain-of-function assays...
December 21, 2018: Clinical and Experimental Pharmacology & Physiology
Hao Yuan, Hongyan Zhao, Jiafeng Wang, Hong Zhang, Lihua Hong, He Li, Hongze Che, Zhimin Zhang
Pulpitis suppressed the level of let-7c-5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let-7c-5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let-7c-5p in DPSCs was up-regulated and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let-7c-5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected...
December 21, 2018: Clinical and Experimental Pharmacology & Physiology
Vikhyat S Bebarta, Normalynn Garrett, Joseph K Maddry, Allyson Arana, Susan Boudreau, Maria Castaneda, Patricia Dixon, David Tanen
Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), norepinephrine (NE), or saline. Thirty swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring...
December 21, 2018: Clinical and Experimental Pharmacology & Physiology
Kai Li, Yunjun Zhang, Dongqi He, Hongbin Han, Lan Yuan
The study introduced a homogeneous orthogonal diffusion model to describe the diffusion pattern of agents in the rat brain. Magnetic Resonance Imaging was performed post-injection of paramagnetic drugs into the caudatum of the rat brain at predetermined time intervals. The signal intensity on Magnetic Resonance Images was converted to agents' concentration, and the standard least square method was employed to estimate the diffusion coefficients. The diffusion coefficients calculated along the three orthogonal axes were D1 = (0...
December 20, 2018: Clinical and Experimental Pharmacology & Physiology
Wenyi Gu, Lihui Wang, Yanheng Wu, Jun-Ping Liu
Recent clinical success of immunotherapy that inhibits the negative immune regulatory pathway programmed cell death protein-1/PD-1 ligand 1 (PD-1/PD-L1) has initiated a new era in the treatment of metastatic cancer. However, greater challenges remain to treat all cancers. The molecular architecture in the immune synapse constituting positive engagements for immune activation and negative checkpoints against immune hyperactivity is regulated dynamically by interaction between proteostasis and tumour microenvironment...
December 19, 2018: Clinical and Experimental Pharmacology & Physiology
Andrzej Kotela, Piotr Wojdasiewicz, Paweł Łęgosz, Sylwia Sarzyńska, Katarzyna Drela, Łukasz Pulik, Beata Kaleta, Monika Kniotek, Jan Borysowski, Łukasz A Poniatowski, Ireneusz Kotela
Hemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of hemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA...
November 29, 2018: Clinical and Experimental Pharmacology & Physiology
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