Effects of Polyunsaturated Phospholipid on Cholesterol Efflux in Vitro and in Experimental Animals and Human Subjects

1987 ◽  
pp. 403-406
Author(s):  
J. Koizumi ◽  
A. Postiglione ◽  
B. L. Knight ◽  
A. K. Soutar ◽  
G. R. Thompson
Keyword(s):  
Cholesterol Efflux ◽  
Human Subjects ◽  
Experimental Animals

Thyroid uptake of 201Thallium and its control by TSH

1981 ◽  
Vol 97 (4) ◽  
pp. 461-465 ◽  
Author(s):  
Morelly L. Maayan ◽  
Eugene M. Volpert ◽  
Eugene J. Fine ◽  
Julius Eisenberg ◽  
Ernesto M. Lopez ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Half Life ◽  
Concentration Ratio ◽  
Human Subjects ◽  
Significant Rise ◽  
Experimental Animals ◽  
Medium Concentration ◽  
Thyroid Uptake

Abstract. Patients injected with 201Thallium (201Tl) for myocardial scanning present good thyroid visualization. Determinations in mice injected with 201Tl indicated a high thyroid/serum concentration ratio (T/S). The 201Tl biological half life (t½) in serum (30-135 s) was much shorter than in thyroid (53-55 h) for human subjects and experimental animals. The 1 h 201Tl T/S ratio was comparable to that of 131I and 99m Tc, indicating presence of a gradient for 201Tl also. Increase of endogenous TSH induced by propylthiouracil led to a significant rise in T/S for 99mTc, 131I and 201Tl, whereas TSH inhibition by feeding l-thyroxine led to decrease in T/S for 99mTc and 201Tl. In vitro thyroid/medium concentration ratio (T/M) of 99mTc and 201Tl was decreased after 20' incubation with ouabain, an inhibitor of the Na+,K+, activated ATP-ase. However, perchlorate in vitro or in vivo failed to diminish the 201Tl T/M ratios or to affect the t½ of 201Tl in human subjects, whereas T/M of 201Tl was depressed by KCl addition to the medium.

THE NEWLY SYNTHESIZED COMPOUND E-5510 IS A HIGHLY POTENT ANTIPLATELET AGENT

1987 ◽  
Author(s):  
K Harada ◽  
T Fujimori ◽  
M Kogushi ◽  
M Kogushi ◽  
I Yamatsu ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Human Subjects ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Inhibitory Effect ◽  
Experimental Animals ◽  
Antiplatelet Effect

Our newly synthesized compound, 4-cyano-5,5-bis(methoxy-phenyl)-4-pentenoic acid (E-5510) has highly potent antiplatelet activity. In this paper, the effects of E-5510 on platelet functions in vitro and ex vivo in human and in various experimental animals are examined.E-5510 inhibited human platelet aggregation induced by collagen, arachidonate, ADP, PAF and epinephrine (IC50: 1.5, 0.7, 2.0, 1.6 and 1.1 uM, respectively). Thrombin-induced platelet aggregation, which was not inhibited by aspirin and U-53059 (lC50s: 100 uM), was also inhibited by this compound (IC50: 21uM). The IC50 of E-5510 in thrombin-induced ATP secretion fromhuman platelets was only 2 uM. Platelet adhesion to a collagen coated disk, whichwas measured by the method of Buchanan et al (Prost. Leuko. Med., 21, 157, 1986) was inhibited by E-5510 (IC50: 19.3 uM) butnot by aspirin and U-53059. In the PRP ofthe guinea pig, the beagle and the monkey, E-5510 inhibited collagen-induced platelet aggregation in vitro to the same degree as in human PRP(IC50: 1.2, 0.6 and 1.5 uM, respectively). After being administered orally to guinea pigs, E-5510 exhibited extremely potent ex vivo inhibitory effect in collagen-induced platelet aggregation with a very low ED50 of 0.05 mg/kg. In contrast, the ED50’s of ticlopidine, aspirin and U-53059 were 300 , 27.2 and 1.0 mg/kg, respectively. In beagles and monkeys E-5510 also showed ex vivo antiplatelet effects at 0.01 and 0.003 mg/kg, respectively. This effect continued for more than 8 hrs. and disappeared within 24 hrs. The antiplatelet effect in human PRP was highly correlated with that in PRP of experimental animals in which the ex vivo effects were confirmed at a very low dose. Thus, E-5510 will ensure to exert the antiplatelet effect after oral administration to human subjects.In summary, E-5510 is unique among the known antiplatelet agents since it has potent inhibitory effects on thrombin-induced platelet activation and platelet adhesion to collagen. It was also shown that this compound had an ex vivo antiplatelet effect at an extremely low ED50. Our results suggest that E-5510 will be a beneficial agent for antiplatelet therapy in humans.

scholarly journals IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 79
Author(s):  
Stephan Wueest ◽  
Eleonora Seelig ◽  
Katharina Timper ◽  
Mark P. Lyngbaek ◽  
Kristian Karstoft ◽  
...  
Keyword(s):  
Exercise Training ◽  
Human Subjects ◽  
Receptor Blockade ◽  
Model Assessment ◽  
Serum Samples ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Homeostatic Model Assessment ◽  
Obese Human

Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (−2.7 ± 8.2% in the placebo vs. −20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.

Analogy Models for Prediction of Human Toxicity

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 103-116
Author(s):  
Sven Hellberg ◽  
Lennart Eriksson ◽  
Jörgen Jonsson ◽  
Fredrik Lindgren ◽  
Michael Sjöström ◽  
...  
Keyword(s):  
Human Subjects ◽  
Toxicity Testing ◽  
In Vitro Cytotoxicity ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
In Vitro Tests ◽  
Human Toxicity ◽  
Efficient Data ◽  
Basal Cytotoxicity

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

Abstract 226: Serum Amyloid A Isoforms and the Capacity to Mediate Cholesterol Efflux

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Hussein Yassine ◽  
Olgica Trenchevska ◽  
Chad Borges ◽  
Dobrin Nedelkov ◽  
Randall W Nelson ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Serum Amyloid A ◽  
Hdl Cholesterol ◽  
Acute Phase Reactant ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Cholesterol Levels ◽  
Acute Phase Reactant Protein

Serum Amyloid A (SAA) is an acute phase reactant protein that exists in multiple isoforms, can form HDL, and participates in cholesterol efflux. In vitro studies suggest that the SAA 2.1 isoform has an increased capacity to mediate cholesterol efflux compared to the other isoforms. We examined SAA isoforms using a novel mass spectrometric immunoassay (MSIA) and HDL’s cholesterol efflux capacity (via ABCA-1 and SR-BI) in samples from 59 subjects with (n=33) and without type 2 diabetes (n=26). SAA 1.1 levels were detectable in 58, SAA 2.1 in 14 and SAA 2.2 in 36 of the 59 subjects. SAA 2.1 levels significantly correlated with SR-BI cholesterol efflux (r=0.71, p=0.01, n=14), but not ABCA-1 mediated efflux (r=0.1, P=0.1). This correlation was not explained by changes in HDL phospholipids, Apo A-I or HDL cholesterol levels. In contrast, SAA 2.2 or 1.1 levels did not correlate with changes in SR-BI or ABCA-1 mediated efflux. Although the SAA 2.1 isoform is less frequently detected in plasma, our data confirm that it is closely linked with HDL mediated cholesterol efflux, particularly that is SR-BI mediated.

scholarly journals A systematic review of the neurobiological aspects of memory in the aging process

2011 ◽  
Vol 5 (4) ◽  
pp. 310-321
Author(s):  
Eduardo Moreira de Oliveira ◽  
Priscilla Tiemi Kissaki ◽  
Tiago Nascimento Ordonez ◽  
Thaís Bento Lima-Silva
Keyword(s):  
Systematic Review ◽  
Aging Process ◽  
Human Subjects ◽  
Basic Research ◽  
Brain Regions ◽  
Morphological Alterations ◽  
Search Terms ◽  
Processing Information ◽  
Normal Human

Abstract A systematic review of the neuroanatomical literature was performed to determine the neuropharmacological aspects most relevant to the study of memory processes. Articles were retrieved using the search terms "biology of memory", "memory and aging", "memory impairment", "elderly and memory," and their equivalents in Portuguese. Of the studies surveyed, five studies dealt with epidemiological and demographic issues, 12 were clinical trials i.e. were based on testing and implementation of instruments in human subjects, 33 studies were basic research involving studies of mice, rats and non-human primates, and biochemical and in vitro trials and finally, 52 studies were literature reviews or book chapters which in our view, fell into this category. Conclusions: The work sought to highlight which neural networks are most involved in processing information, as well as their location within brain regions and the way in which neurotransmitters interact with each other for the formation of these memories. Moreover, it was shown how memory changes during the normal human aging process, both positively and negatively, by analyzing the morphological alterations that occur in the brain of aging individuals.

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