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  • Aerospace Medicine  (4)
  • Multiphase, Granular, and Particle-Laden Flows  (2)
  • SDS-PAGE  (2)
  • brain  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Pb-induced alterations in tyrosine hydroxylase activity in rat brain (1997)
    Springer
    Molecular and cellular biochemistry 175 (1997), S. 137-141 
    Details
    ISSN: 1573-4919
    Keywords: Pb ; dopamine biosynthesis ; tyrosine hydroxylase ; brain ; SDS-PAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Our previous studies have shown that exposure to low levels of Pb results in significant reductions in dopamine (DA) and its metabolites (3,4-dihyroxyphenylacetic acid, DOPAC and homovanillic acid, HVA) in nucleus acumbens (NA). This area of brain receives dopaminergic projections from the ventral tegmentum and is considered vital in manifestation of many behavioral responses. Similarly, basal and K+-induced release of DA was found significantly reduced in the Pb-exposed rats as compared to the controls in this brain region. Additional studies indicated that acute infusion of Pb in nucleus acumbens caused significant release of DA. Based on these observations it was postulated that the reductions in DA contents and in the basal and stimulus-induced release of DA in NA were manifestations of attenuated dopaminergic activity in this brain region. However, the mechanism of this attenuation is not yet clear. Studies reported here were designed to evaluate the role of a key regulatory enzy me in biosynthesis of DA, i.e. tyrosine hydroxylase (TH) in Pb-induced reductions in dopaminergic activity. The results of these studies indicated that 50 and 500 ppm Pb produced 22.8 and 56% inhibition of TH activity in vitro respectively, and that the enzyme activity was reduced to 43% in rats exposed to 50 ppm lead for 30 days as compared to the controls. The alterations in TH activity in Pb-exposed animals were further confirmed by Western blot analysis. Collectively, these results suggest that Pb-induced inhibition of TH activity in rat brain may contribute to the reductions in dopaminergic activity observed in Pb-exposed animals. (Mol Cell Biochem 175: 137–141, 1997)
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006891830182
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Region - specific alterations in tyrosine hydroxylase activity in rats exposed to lead (1998)
    Springer
    Molecular and cellular biochemistry 189 (1998), S. 19-24 
    Details
    ISSN: 1573-4919
    Keywords: brain ; pb ; tyrosine hydroxylase ; SDS-PAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies from our laboratory showed that subchronic exposure to low levels of Pb resulted in significant decrease in dopamine (DA) content, attenuation of stimulus-induced release of DA in the dopaminergic projection area of nucleus accumbens (NA), and alterations in tyrosine hydroxylase (TH) activity in rat whole brain homogenates. The present study reported here was conducted to assess the functional integrity of DA synthesis in different brain regions of rats subchronically (90-days) exposed to 50 ppm Pb by measuring the activity of the rate limiting enzyme, tyrosine hydroxylase, in seven brain regions. In Pb-exposed rats, TH activity was reduced in two of the seven brain regions investigated, i.e., nucleus accumbens (42% reduction) and frontal cortex (61% reduction) when compared to controls. In contrast, Pb exposure did not affect the TH activity in cerebellum, brainstem, hippocampus, hypothalamus and striatum. The changes in TH activity in nucleus accumbens (NA) and frontal cortex (FC) in Pb-exposed rats were further confirmed by Western blot analysis using TH polyclonal antibody. Collectively, these results indicate that low level subchronic Pb exposure may affect TH protein in these brain regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006896111280
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  • 3
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    Caustics-induced coalescence of small droplets near a vortex (2017)
    American Physical Society (APS)
    Details
    Publication Date: 2017-03-02
    Description: Author(s): P. Deepu, S. Ravichandran, and Rama Govindarajan A simple model of droplets being centrifuged out of a vortex shows that caustics lead to a rapid formation of large drops through coalescence. Polydispersity in droplet size enhances this process. [Phys. Rev. Fluids 2, 024305] Published Tue Feb 28, 2017
    Keywords: Multiphase, Granular, and Particle-Laden Flows
    Electronic ISSN: 2469-990X
    Topics: Physics
    Published by American Physical Society (APS)
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    PAPER CURRENT
  • 4
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    Solid-on-solid contact in a sphere-wall collision in a viscous fluid (2018)
    American Physical Society (APS)
    Details
    Publication Date: 2018-04-10
    Description: Author(s): Sumit Kumar Birwa, G. Rajalakshmi, Rama Govindarajan, and Narayanan Menon New experiments show that collisions between a sphere and a plane immersed in a viscous fluid involve direct mechanical contact, in contrast to expectations based on earlier theory. An electrical probe is used to monitor short-time mechanics of contact formation during the rebound of the sphere. [Phys. Rev. Fluids 3, 044302] Published Mon Apr 09, 2018
    Keywords: Multiphase, Granular, and Particle-Laden Flows
    Electronic ISSN: 2469-990X
    Topics: Physics
    Published by American Physical Society (APS)
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  • 5
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    Effects of Modeled Microgravity on Expression Profiles of Micro RNA in Human Lymphoblastoid Cells (2010)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: Among space radiation and other environmental factors, microgravity or an altered gravity is undoubtedly the most significant stress experienced by living organisms during flight. In comparison to the static 1g, microgravity has been shown to alter global gene expression patterns and protein levels in cultured cells or animals. Micro RNA (miRNA) has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. miRNA represents a class of single-stranded noncoding regulatory RNA molecules (~ 22 nt) that control gene expressions by inhibiting the translation of mRNA to proteins. However, very little is known on the effect of altered gravity on miRNA expression. We hypothesized that the miRNA expression profile will be altered in zero gravity resulting in regulation of the gene expression and functional changes of the cells. To test this hypothesis, we cultured TK6 human lymphoblastoid cells in Synthecon s Rotary cell culture system (bioreactors) for 72 h either in the rotating (10 rpm) to model the microgravity in space or in the static condition. The cell viability was determined before and after culturing the cells in the bioreactor using both trypan blue and guava via count. Expressions of a panel of 352 human miRNA were analyzed using the miRNA PCRarray. Out of 352 miRNAs, expressions of 75 were significantly altered by a change of greater than 1.5 folds and seven miRNAs were altered by a fold change greater than 2 under the rotating culture condition. Among these seven, miR-545 and miR-517a were down regulated by 2 folds, whereas miR-150, miR-302a, miR-139-3p, miR-515-3p and miR-564 were up regulated by 2 to 8 folds. To confirm whether this altered miRNA expression correlates with gene expression and functional changes of the cells, we performed DNA Illumina Microarray Analysis and validated the related genes using q-RT PCR.
    Keywords: Aerospace Medicine
    Type: JSC-CN-22412 , 18th IAA Humans in Space Symposium: The Next Golden Age; Apr 11, 2011 - Apr 15, 2011; Houston, TX; United States
    Format: application/pdf
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  • 6
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    Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space (2008)
    In:  Other Sources
    Details
    Publication Date: 2019-07-19
    Description: The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less significantly after 1 and 2 hours. At 2 hours approximately 20% of the drug still remained in the circulation. After 96 hrs of HLU the changes in acetaminophen PK were less prominent. These data indicate that short term HLU causes significant changes in acetaminophen PK most likely associated with HUL-related hemodynamic changes. However, after 96 hour these changes diminished. This suggests hemodynamic adaptation to the HUL conditions that possibly occurs also in real space conditions.
    Keywords: Aerospace Medicine
    Type: 43rd Annual ACLPS Meeting; Jun 05, 2008 - Jun 07, 2008; Philadelphia, PA; United States
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    NASA TECHNICAL REPORTS
  • 7
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    Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice (2007)
    In:  Other Sources
    Details
    Publication Date: 2019-07-19
    Description: The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half-life time in the HLU mice points towards slower drug elimination from the circulation.
    Keywords: Aerospace Medicine
    Type: 79th Annual Scientific Meeting of the Aerospace Medical Association; May 11, 2008 - May 15, 2008; Boston, MA; United States
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  • 8
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    Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment (2005)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.
    Keywords: Aerospace Medicine
    Type: In vitro cellular & developmental biology. Animal (ISSN 1071-2690); 41; 4-Mar; 118-23
    Format: text
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