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Weijun Wang, Hee-Yeon Cho, Rachel Rosenstein-Sisson, Nagore I Marín Ramos, Ryan Price, Kyle Hurth, Axel H Schönthal, Florence M Hofman, Thomas C Chen
OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM...
April 14, 2017: Journal of Neurosurgery
Magdalena Kurnik-Lucka, Krzysztof Gil, Andrzej Bugajski, Agata Furgała, Piotr Thor
OBJECTIVES: Previous studies have reported that exogenous salsolinol might contribute to myenteric cell death and altered gastrointestinal motility. Because the entire gut mucosal, entero-endocrine and motor functions are integrated by the enteric nervous system, the aim of the present study was to investigate if prolonged intraperitoneal salsolinol administration alters basic metabolism and nutritional parameters in adult Wistar rats fed normal or high-fat diets. METHODS: Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol with ALZET osmotic mini-pumps for 2 or 4 weeks and fed either a normal or high-fat diet...
December 2016: Neuro Endocrinology Letters
Ai-Li Guan, Tao He, Yi-Bing Shao, Yi-Fan Chi, Hong-Yan Dai, Yan Wang, Li Xu, Xuan Yang, Hua-Min Ding, Shang-Lang Cai
BACKGROUND: Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy...
February 5, 2017: Chinese Medical Journal
Jesus-Servando Medel-Matus, Don Shin, Raman Sankar, Andrey Mazarati
Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (RN)-prefrontal cortex (PFC) serotonergic pathway and in the locus coeruleus (LC)-PFC noradrenergic pathway underlies depressive- and impulsive-like behavioral deficits respectively. We examined possible mechanisms leading to the monoamine dysfunction in brainstem efferents, namely modulatory effects of the neuropeptide galanin on serotonin (5-HT) and norepinephrine (NE) signaling...
March 2017: Experimental Neurology
Mengcheng Shen, Jude Morton, Sandra T Davidge, Zamaneh Kassiri
Hypertension is associated with hypertrophy and hyperplasia of smooth muscle cells (SMCs). Disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme reported to mediate SMC hypertrophy through activation of epidermal growth factor receptor (EGFR). We investigated the role of ADAM17 in Ang II-induced hypertension and end-organ damage. VSMC was isolated from mice with intact ADAM17 expression (Adam17(f/f)) or lacking ADAM17 in the SMC (Adam17(f/f)/Cre(Sm22)). Human VSMCs were isolated from the aorta of donors, and ADAM17 deletion was achieved by siRNA transfection...
February 2017: Journal of Molecular and Cellular Cardiology
Liliana Germán-Castelán, Joaquín Manjarrez-Marmolejo, Aliesha González-Arenas, Ignacio Camacho-Arroyo
BACKGROUND AND AIMS: Progesterone (P) is a steroid hormone involved in the development of several types of cancer including astrocytomas, the most common and malignant brain tumors. We undertook this study to investigate the effects of P on the growth and infiltration of a tumor caused by the xenotransplant of U87 cells derived from a human astrocytoma grade IV (glioblastoma) in the cerebral cortex of male rats and the participation of intracellular progesterone receptor (PR) on these effects...
August 2016: Archives of Medical Research
Yong Cao, Tian-Ding Wu, Hao Wu, Ye Lang, Dong-Zhe Li, Shuang-Fei Ni, Hong-Bin Lu, Jian-Zhong Hu
MicroRNA-210 (miR-210) was initially reported to be associated with hypoxia and plays a vital role in modulating angiogenesis. However, the potential effect and underlying mechanisms of miR-210 activity in rat spinal cord injury (SCI) have not yet been fully illuminated. In the present study, differential microRNA expression after SCI was determined by Microarray analysis. To explore the effect of miR-210 after SCI, we intrathecally injected agomir-210 with Alzet Osmotic Pumps to up-regulated the endogenous miR-210 expression...
January 15, 2017: Brain Research
Veronika Aleksandrovych, Magdalena Kurnik, Magdalena Białas, Andrzej Bugajski, Piotr Thor, Krzysztof Gil
Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis...
2016: Folia Medica Cracoviensia
S Novella, X Vidal-Gómez, A Mompeón, D Pérez-Cremades, G Segarra, P Medina, C Hermenegildo
OBJECTIVE: The role of ageing in the development of vascular disease is currently associated with a rise in oxidative stress. Thromboxane A2 (TXA2) is an inflammatory and oxidant endogenous vasoconstrictor which action increases with ageing and lack of estrogens, both conditions found in menopause. Our aim was to determine superoxide anion (O2-) levels in response to TXA2 in aortic vascular tissue from senescent and ovariectomized mice and the role of cyclooxygenase as source of O2-. DESIGN AND METHOD: Senescence accelerated mice (SAM) were used in this study...
September 2016: Journal of Hypertension
Ayahisa Watanabe, Kei Mayumi, Kyohei Nishimura, Hiromi Osaki
1-Aminobenzotriazole (ABT) is a well-known in vivo nonspecific inhibitor of cytochrome P450 (CYP) enzymes. An effective dosing regimen of ABT for a multiple-administration study is needed to conduct pharmacological studies for proof-of-concept, although it has been established for single-administration study, to characterize the pharmacokinetics of drug candidates. This study demonstrated a suitable dosing vehicle of ABT for continuous administration and increased exposure to antipyrine, which is a nonspecific probe of CYP, using ABT for a long period in mice...
September 2016: Biopharmaceutics & Drug Disposition
Qiqi Long, Xishi Liu, Sun-Wei Guo
BACKGROUND: Surgery is currently the mainstay treatment for solid tumors and many benign diseases, including endometriosis, and women tend to receive substantially more surgeries than men mainly because of gynecological and cosmetic surgeries. Despite its cosmetic, therapeutic, or even life-saving benefits, surgery is reported to increase the cancer risk and promotes cancer metastasis. Surgery activates adrenergic signaling, which in turn suppresses cell-mediated immunity and promotes angiogenesis and metastasis...
September 2016: American Journal of Obstetrics and Gynecology
I A Gallardo-Ortíz, S N Rodríguez-Hernández, J J López-Guerrero, L Del Valle-Mondragón, P López-Sánchez, R M Touyz, R Villalobos-Molina
The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1 -adrenoceptors (α1 -ARs) expression was explored. Alzet(®) minipumps filled with Ang II (200 ng kg(-1)  min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective α1D -AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses...
September 2015: Autonomic & Autacoid Pharmacology
Loqman A Mohamed, Jeffrey N Keller, Amal Kaddoumi
Recently, we showed that rivastigmine decreased amyloid-β (Aβ) brain load in aged rats by enhancing its clearance across the blood-brain barrier (BBB) via upregulation of P-glycoprotein (P-gp) and low-density lipoprotein receptor-related protein 1 (LRP1). Here, we extend our previous work to clarify P-gp role in mediating rivastigmine effect on Aβ brain levels and neuroprotection in a mouse model of Alzheimer's disease (AD) that expresses different levels of P-gp. APPSWE mice were bred with mdr1a/b knockout mice to produce littermates that were divided into three groups; APP(+)/mdr1(+/+), APP(+)/mdr1(+/-) and APP(+)/mdr1(-/-)...
April 2016: Biochimica et Biophysica Acta
Yung-Ting Kuo, Ping-Hsiao Shih, Shu-Huei Kao, Geng-Chang Yeh, Horng-Mo Lee
Denervation-mediated skeletal muscle atrophy results from the loss of electric stimulation and leads to protein degradation, which is critically regulated by the well-confirmed transcriptional co-activator peroxisome proliferator co-activator 1 alpha (PGC-1α). No adequate treatments of muscle wasting are available. Pyrroloquinoline quinone (PQQ), a naturally occurring antioxidant component with multiple functions including mitochondrial modulation, demonstrates the ability to protect against muscle dysfunction...
2015: PloS One
Ya-Hui Ko, Ming-Shian Tsai, Ru-Wen Chang, Chun-Yi Chang, Chih-Hsien Wang, Ming-Shiou Wu, Jin-Tung Liang, Kuo-Chu Chang
It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg(-1) d(-1)) for 2 weeks...
2015: Frontiers in Physiology
Aurélie Ledreux, Heather A Boger, Vanessa K Hinson, Kelsey Cantwell, Ann-Charlotte Granholm
The anti-Parkinsonian drug rasagiline is a selective, irreversible inhibitor of monoamine oxidase and is used in the treatment of Parkinson׳s disease (PD). Its postulated neuroprotective effects may be attributed to MAO inhibition, or to its propargylamine moiety. The major metabolite of rasagiline, aminoindan, has shown promising neuroprotective properties in vitro but there is a paucity of studies investigating in vivo effects of this compound. Therefore, we examined neuroprotective effects of rasagiline and its metabolite aminoindan in a double lesion model of PD...
January 15, 2016: Brain Research
Daniel G Donner, Grace E Elliott, Belinda R Beck, Andrew C Bulmer, Alfred K Lam, John P Headrick, Eugene F Du Toit
The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX)...
January 2016: Endocrinology
Shaul Schreiber, Miaad Bader, Vardit Rubovitch, Chaim G Pick
OBJECTIVES: Methylphenidate (MPH), a psychostimulant used for treatment of attention deficit hyperactivity disorder (ADHD), is widely used by patients on antidepressants and methadone maintenance treatment (MMT). Preclinical studies showed MPH to exert analgesic effects when given alone or with morphine. METHODS: Using the hotplate assay on mice, we studied the interaction of acute doses of MPH with sub-threshold doses of methadone and different antidepressant medications and the interaction of increasing doses of MPH with chronic methadone...
November 3, 2015: World Journal of Biological Psychiatry
Monika Liguz-Lecznar, Renata Zakrzewska, Malgorzata Kossut
Tumor necrosis factor-α (TNF-α) is one of the key players in stroke progression and can interfere with brain functioning. We previously documented an impairment of experience-dependent plasticity in the cortex neighboring the stroke-induced lesion, which was accompanied with an upregulation of Tnf-α level in the brain of ischemic mice 1 week after the stroke. Because TNF receptor 1 (TnfR1) signaling is believed to be a major mediator of the cytotoxicity of Tnf-α through activation of caspases, we used an anti-inflammatory intervention aimed at Tnf-α R1 pathway, in order to try to attenuate the detrimental effect of post-stroke inflammation, and investigated if this will be effective in protecting plasticity in the infarct proximity...
October 2015: Neurobiology of Aging
Suleyman Sandal, Suat Tekin, Fatma Burcu Seker, Ali Beytur, Nigar Vardi, Cemil Colak, Tuba Tapan, Sedat Yildiz, Bayram Yilmaz
Apelin is a novel bioactive peptide as the endogenous ligand for APJ. Apelin and APJ have also been identified in the testis, hypothalamic nuclei such as arcuate, supraoptic and paraventricular nuclei, implicating roles in the control of reproduction. Therefore, the present study was designed to investigate the effects of chronic central infusion of apelin-13 on LH, FSH and testosterone levels and testis morphology. 21 Wistar-Albino male rats received continuous intracerebroventricular infusion via Alzet osmotic mini pumps filled artificial cerebrospinal fluid (vehicle) or apelin-13 at concentrations of 1 or 10 nmol (10 μl/h) for seven days...
August 18, 2015: Neuroscience Letters
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