scholarly journals Age-dependent changes in phenytoin tissue bindings in rats: Comparison between in vivo and in vitro tissue-to-blood partition coefficients (Kp values) of phenytoin.

1987 ◽  
Vol 10 (9) ◽  
pp. 470-477 ◽  
Author(s):  
YOSHITERU KATO ◽  
JUNJI HIRATE ◽  
KAZUO SAKAGUCHI ◽  
MASAHARU UENO ◽  
ISAMU HORIKOSHI
Keyword(s):  
Partition Coefficients ◽  
Age Dependent

Equilibrium distribution of radioxenon in tissue: xenon-hemoglobin association curve

1961 ◽  
Vol 16 (6) ◽  
pp. 1065-1070 ◽  
Author(s):  
Hadley L. Conn
Keyword(s):  
Partition Coefficients ◽  
Equilibrium Distribution ◽  
Hemoglobin Concentration ◽  
Gas Diffusion ◽  
In Vivo Studies ◽  
Diffusion Method ◽  
Body Tissues ◽  
Gas Diffusion Method

In vitro and in vivo studies were made of the equilibrium distribution of radioxenon in various organs and tissues of the dog and the xenon uptake compared with a water standard. Tissue-blood partition coefficients were calculated. The radioxenon-hemoglobin association curve was determined for dog and human hemoglobin and methemoglobin. The uptake of radioxenon by blood, due in particular to xenon-hemoglobin affinity, was appreciably greater than uptake either by water or by most other body tissues. Fat and brain were notable exceptions. Consequently, tissue-blood partition coefficients were about eight for fat, one for brain, and significantly less than one for other tissues studied. Acceptable accuracy for blood flow determinations with a radioxenon inert gas diffusion method would seem to depend on the use of a partition coefficient correction in turn corrected at least for the existing hemoglobin concentration. The uptake of xenon by hemoglobin had the characteristics of a solubility or a quasi-solubility phenomenon. The problem of the nature of the interaction is apparently not resolved. Submitted on June 19, 1961

scholarly journals In Vivo Quasi-Elastic Light Scattering Eye Scanner Detects Molecular Aging in Humans

2020 ◽  
Vol 75 (9) ◽  
pp. e53-e62
Author(s):  
Olga Minaeva ◽  
Srikant Sarangi ◽  
Danielle M Ledoux ◽  
Juliet A Moncaster ◽  
Douglas S Parsons ◽  
...  
Keyword(s):  
Light Scattering ◽  
Human Lens ◽  
Fetal Life ◽  
Healthy Human ◽  
Elastic Light Scattering ◽  
Lens Proteins ◽  
Age Dependent ◽  
Molecular Aging

Abstract The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. We used quasi-elastic light scattering (QLS) to measure age-dependent signals in lenses of healthy human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro. Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.

scholarly journals Age-dependent mechanical properties of rat femur: Measured in vivo and in vitro

1991 ◽  
Vol 62 (3) ◽  
pp. 248-252 ◽  
Author(s):  
Karl Indrekvam ◽  
Otto Schnell Husby ◽  
Nils R. Gjerdet ◽  
Lars B. Engester ◽  
Norvald Langeland
Keyword(s):  
Mechanical Properties ◽  
Rat Femur ◽  
Age Dependent

scholarly journals Protein modification during biological aging: selective tyrosine nitration of the SERCA2a isoform of the sarcoplasmic reticulum Ca2+-ATPase in skeletal muscle

1999 ◽  
Vol 340 (3) ◽  
pp. 657-669 ◽  
Author(s):  
Rosa I. VINER ◽  
Deborah A. FERRINGTON ◽  
Todd D. WILLIAMS ◽  
Diana J. BIGELOW ◽  
Christian SCHÖNEICH
Keyword(s):  
Skeletal Muscle ◽  
Atpase Activity ◽  
Biological Aging ◽  
Tyrosine Nitration ◽  
Age Dependent ◽  
Slow Twitch Muscle ◽  
Slow Twitch ◽  
Fast Twitch

The accumulation of covalently modified proteins is an important hallmark of biological aging, but relatively few studies have addressed the detailed molecular-chemical changes and processes responsible for the modification of specific protein targets. Recently, Narayanan et al. [Narayanan, Jones, Xu and Yu (1996) Am. J. Physiol. 271, C1032-C1040] reported that the effects of aging on skeletal-muscle function are muscle-specific, with a significant age-dependent change in ATP-supported Ca2+-uptake activity for slow-twitch but not for fast-twitch muscle. Here we have characterized in detail the age-dependent functional and chemical modifications of the rat skeletal-muscle sarcoplasmic-reticulum (SR) Ca2+-ATPase isoforms SERCA1 and SERCA2a from fast-twitch and slow-twitch muscle respectively. We find a significant age-dependent loss in the Ca2+-ATPase activity (26% relative to Ca2+-ATPase content) and Ca2+-uptake rate specifically in SR isolated from predominantly slow-twitch, but not from fast-twitch, muscles. Western immunoblotting and amino acid analysis demonstrate that, selectively, the SERCA2a isoform progressively accumulates a significant amount of nitrotyrosine with age (≈ 3.5±0.7 mol/mol of SR Ca2+-ATPase). Both Ca2+-ATPase isoforms suffer an age-dependent loss of reduced cysteine which is, however, functionally insignificant. In vitro, the incubation of fast- and slow-twitch muscle SR with peroxynitrite (ONOO-) (but not NO/O2) results in the selective nitration only of the SERCA2a, suggesting that ONOO- may be the source of the nitrating agent in vivo. A correlation of the SR Ca2+-ATPase activity and covalent protein modifications in vitro and in vivo suggests that tyrosine nitration may affect the Ca2+-ATPase activity. By means of partial and complete proteolytic digestion of purified SERCA2a with trypsin or Staphylococcus aureus V8 protease, followed by Western-blot, amino acid and HPLC-electrospray-MS (ESI-MS) analysis, we localized a large part of the age-dependent tyrosine nitration to the sequence Tyr294-Tyr295 in the M4-M8 transmembrane domain of the SERCA2a, close to sites essential for Ca2+ translocation.

scholarly journals Autoimmunity-Associated Gut Commensals Modulate Gut Permeability and Immunity in Humanized Mice

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 529-536 ◽  
Author(s):  
Baskar Balakrishnan ◽  
David Luckey ◽  
Veena Taneja
Keyword(s):  
Immune Response ◽  
Type Ii Collagen ◽  
Gut Permeability ◽  
Associated Bacteria ◽  
Epithelial Integrity ◽  
Inflammatory Monocytes ◽  
Age Dependent ◽  
Th17 Cytokines

Abstract Objective Although the etiology of rheumatoid arthritis (RA) is unknown, recent studies have led to the concept that gut dysbiosis may be involved in onset. In this study, we aimed to determine if human gut commensals modulate the immune response and gut epithelial integrity in DQ8 mice. Methods DQ8 mice were orally gavaged with RA-associated (Eggerthella lenta or Collinsella aerofaciens) and non-associated (Prevotella histicola or Bifidobacterium sp.) on alternate days for 1 week in naïve mice. Some mice were immunized with type II collagen and oral gavage continued for 6 weeks and followed for arthritis. Epithelial integrity was done by FITC-Dextran assay. In addition, cytokines were measured in sera by ELISA and various immune cells were quantified using flow cytometry. Results Gut permeability was increased by the RA-associated bacteria and was sex and age-dependent. In vivo and in vitro observations showed that the RA-non-associated bacteria outgrow the RA-associated bacteria when gavaged or cultured together. Mice gavaged with the RA-non-associated bacteria produced lower levels of pro-inflammatory MCP-1 and MCP-3 and had lower numbers of Inflammatory monocytes CD11c+Ly6c+, when compared to controls. E. lenta treated naïve mice produce Th17 cytokines. Conclusions Our studies suggest that gut commensals influence immune response in and away from the gut by changing the gut permeability and immunity. Dysbiosis helps the growth of RA-associated bacteria and reduces the beneficial bacteria.

scholarly journals Species differences in the metabolism and excretion of sulphasomidine and sulphamethomidine

1969 ◽  
Vol 111 (2) ◽  
pp. 173-179 ◽  
Author(s):  
J W Bridges ◽  
S R Walker ◽  
R T Williams
Keyword(s):  
Partition Coefficients ◽  
Species Differences ◽  
Species Difference ◽  
Acetyl Derivative ◽  
The Other ◽  
Main Metabolite ◽  
Monkey Liver ◽  
Liver Homogenates

1. The excretion of 2,4-dimethyl-6-sulphanilamidopyrimidine (sulphasomidine; Elkosin) and 4-methoxy-2-methyl-6-sulphanilamidopyrimidine (sulphamethomidine) given orally was examined in man, rhesus monkey, rabbit and rat. 2. About 70% of sulphasomidine (0·1g./kg.) is excreted mainly unchanged in the urine by these species in 24hr.; less than 15% of the dose is acetylated and there is no marked species difference in the fate of this drug. 3. Sulphamethomidine is excreted more slowly than sulphasomidine, and in the rat, rabbit and monkey the main metabolite is the N4-acetyl derivative. In man, only 20–30% of the dose is excreted in 24hr. and nearly 70% of this is sulphamethomidine N1-glucuronide, which is also excreted by the monkey but not by the rat or rabbit. There is therefore a marked species difference in the metabolism of sulphamethomidine. 4. Sulphamethomidine N1-glucuronide was synthesized and shown to be identical with the glucuronide isolated from monkey urine. 5. Sulphasomidine, sulphamethomidine and sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) were acetylated by rabbit or monkey liver homogenates. Although sulphasomidine is poorly acetylated in vivo, it is acetylated in vitro at rates comparable with those of the other two drugs. 6. The solubilities, partition coefficients and plasma-protein-binding of the drugs were measured. 7. The results are discussed.

scholarly journals The Function of TIF2/GRIP1 in Mouse Reproduction Is Distinct from Those of SRC-1 and p/CIP

2002 ◽  
Vol 22 (16) ◽  
pp. 5923-5937 ◽  
Author(s):  
Martine Gehin ◽  
Manuel Mark ◽  
Christine Dennefeld ◽  
Andrée Dierich ◽  
Hinrich Gronemeyer ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Stromal Cells ◽  
Critical Role ◽  
Physiological Role ◽  
Mouse Homolog ◽  
Nuclear Receptor Coactivators ◽  
Age Dependent ◽  
Testicular Degeneration

ABSTRACT Human TIF2 (hTIF2) is a member of the p160 family of nuclear receptor coactivators, which includes SRC-1 and p/CIP. Although the functions of hTIF2 and of its mouse homolog (GRIP1 or mTIF2) have been clearly established in vitro, their physiological role remains elusive. Here, we have generated mice lacking mTIF2/GRIP1 and examined their phenotype with a particular emphasis on reproductive functions. TIF2−/− mice are viable, but the fertility of both sexes is impaired. Male hypofertility is due to defects in both spermiogenesis (teratozoospermia) and age-dependent testicular degeneration, and TIF2 expression appears to be essential for adhesion of Sertoli cells to germ cells. Female hypofertility is due to a placental hypoplasia that most probably reflects a requirement for maternal TIF2 in decidua stromal cells that face the developing placenta. We conclude that TIF2 plays a critical role in mouse reproductive functions, whereas previous reports have not revealed serious fertility impairment in SRC-1−/− or p/CIP−/− mutants. Thus, even though the three p160 coactivators exhibit strong sequence homology and similar activity in assays in vitro, they play distinct physiological roles in vivo, as their genetic eliminations result in distinct pathologies.

scholarly journals Age-dependent decrease in human cardiac β-adrenergic and muscarinic receptor function: in vitro and in vivo study

1998 ◽  
Vol 31 ◽  
pp. 177
Author(s):  
O.-E. Brodde ◽  
K. Becker ◽  
J. Jakubetz ◽  
U. Konschak ◽  
U. Poller ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
In Vivo Study ◽  
Receptor Function ◽  
Age Dependent
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