Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers

Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load. Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II). Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6. Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.

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Abstract 17545: Vasoconstriction During Mental Stress Predicts Severity of Mental Stress Induced Myocardial Ischemia

Circulation ◽

10.1161/circ.132.suppl_3.17545 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Nino Isakadze ◽

Ayman Alkhoder ◽

Arshed A Quyyumi ◽

Viola Vaccarino ◽

J. Douglas Bremner ◽

...

Keyword(s):

Risk Factors ◽

Dose Response ◽

Vascular Function ◽

Mental Stress ◽

Stress Test ◽

Recovery Phase ◽

Response Relationship ◽

Dose Response Relationship ◽

Peripheral Vasoconstriction ◽

Pulse Wave Amplitude

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. Hypothesis: We hypothesized that increased digital microvascular constriction during both mental stress and recovery are predictive of increased severity of mental stress ischemia. Methods: We evaluated 204 patients with stable CAD with high quality vascular data using a standardized mental stress test using a public speaking task. Peripheral artery tonometry (PAT) (Itamar Inc) was used to assess digital microvascular tone. Vasoconstriction was calculated as the ratio of pulse wave amplitude during speech/recovery and the last 3 minutes of baseline, with lower ratio indicating more vasoconstriction. 99mTc sestamibi myocardial perfusion imaging was performed at rest and with mental stress. A summed difference score (SDS) quantifying severity of reversible perfusion defects (inducible ischemia) comparing rest and stress images was computed using a standard 17-segment model. Four categories of increasing severity were based on cut points of 0, 3, and 6. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Each category of increase in ischemia severity was associated with a 10% (p=0.04) decrease in speech PAT ratio (Figure) and 11% (p=0.02) decrease in recovery PAT ratio. After multivariable adjustment for sociodemographics, traditional risk factors, medical history, medication use, and psychological risk factors, the associations persisted, with B=-11%, p=0.02 for speech PAT ratio, and B=-8%, p=0.04 for recovery ratio. Conclusion: Peripheral vasoconstriction during mental stress speech as well as recovery predicts MSI severity in a dose-response relationship.

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A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

Acta Endocrinologica ◽

10.1530/acta.0.0410268 ◽

1962 ◽

Vol 41 (2) ◽

pp. 268-273 ◽

Cited By ~ 9

Author(s):

Ralph I. Dorfman

Keyword(s):

Dose Response ◽

Subcutaneous Injection ◽

Response Relationship ◽

Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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Dose-response relationship between lymph insulin and glucose uptake reveals enhanced insulin sensitivity of peripheral tissues

Diabetes ◽

10.2337/diabetes.41.2.241 ◽

1992 ◽

Vol 41 (2) ◽

pp. 241-253 ◽

Cited By ~ 16

Author(s):

Y. J. Yang ◽

I. Hope ◽

M. Ader ◽

R. A. Poulin ◽

R. N. Bergman

Keyword(s):

Insulin Sensitivity ◽

Glucose Uptake ◽

Dose Response ◽

Response Relationship ◽

Dose Response Relationship ◽

Peripheral Tissues

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Faculty Opinions recommendation of Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13741.471237 ◽

2006 ◽

Author(s):

Paolo Vineis

Keyword(s):

Lung Cancer ◽

Dose Response ◽

Response Relationship ◽

Dose Response Relationship ◽

Cooking Fumes

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Faculty Opinions recommendation of Activation of mTORC1 signalling in rat skeletal muscle is independent of the EC-coupling sequence but dependent on tension per se in a dose-response relationship.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736043008.793568723 ◽

2019 ◽

Author(s):

Craig A Goodman

Keyword(s):

Skeletal Muscle ◽

Dose Response ◽

Response Relationship ◽

Rat Skeletal Muscle ◽

Dose Response Relationship ◽

Ec Coupling ◽

Per Se ◽

Coupling Sequence

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The dose-response relationship between interval-training and VO2max in well-trained endurance runners: A systematic review

Journal of Sports Sciences ◽

10.1080/02640414.2021.1876313 ◽

2021 ◽

pp. 1-18

Author(s):

Arran Parmar ◽

Thomas W. Jones ◽

Philip, R. Hayes

Keyword(s):

Systematic Review ◽

Dose Response ◽

Interval Training ◽

Response Relationship ◽

Dose Response Relationship ◽

Endurance Runners

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Mathematical Interpretation of the Pharmacodynamics of Homoeopathic Medicines

Homœopathic Links ◽

10.1055/s-0040-1717132 ◽

2021 ◽

Vol 34 (01) ◽

pp. 003-016

Author(s):

John Michel Warner

Keyword(s):

Immune System ◽

Immune Responses ◽

Dose Response ◽

Oral Route ◽

Response Relationship ◽

Dose Response Relationship ◽

Force Line ◽

Administration Routes ◽

Medicinal Substances ◽

Medicine Administration

AbstractAccording to Hahnemann, homoeopathic medicines must be great immune responses inducers. In crude states, these medicines pose severe threats to the immune system. So, the immune-system of an organism backfires against the molecules of the medicinal substances. The complex immune response mechanism activated by the medicinal molecules can handle any threats which are similar to the threats posed by the medicinal molecules. The intersectional operation of the two sets, medicine-induced immune responses and immune responses necessary to cure diseases, shows that any effective homoeopathic medicine, which is effective against any disease, can induce immune responses which are necessary to cure the specific disease. In this article, this mechanism has been exemplified by the action of Silicea in human body. Also, a neuroimmunological assessment of the route of medicine administration shows that the oral cavity and the nasal cavity are two administration-routes where the smallest doses (sometimes even few molecules) of a particular homoeopathic medicine induce the most effective and sufficient (in amount) purgatory immune responses. Administering the smallest unitary doses of Silicea in the oral route can make significant changes in the vital force line on the dose–response relationship graph. The dose–response relationship graph further implicates that the most effective dose of a medicine must be below the lethality threshold. If multiple doses of any medicine are administered at same intervals, the immune-system primarily engages with the medicinal molecules; but along the passage of time, the engagement line splits into two: one engages with the medicinal molecules and another engages with diseases. The immune system's engagement with the diseases increases along the passage of time, though the engagement with the medicinal molecules gradually falls with the administration of descending doses. Necessarily, I have shown through mathematical logic that the descending doses, though they seem to be funny, can effectively induce the most effective immune responses.

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