The Exercise-Dose Response Curve to Nifedipine in β-Blocked Patients with Stable Angina Pectoris

SummaryElevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen β-gene.The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the BclI polymorphism of the fibrinogen β-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA).In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student t-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen β-gene polymorphisms.Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen β-gene polymorphisms.

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OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

Acta Endocrinologica ◽

10.1530/acta.0.0560619 ◽

1967 ◽

Vol 56 (4) ◽

pp. 619-625 ◽

Cited By ~ 1

Author(s):

Hans Jacob Koed ◽

Christian Hamburger

Keyword(s):

Ascorbic Acid ◽

Luteinizing Hormone ◽

Dose Response ◽

Response Curve ◽

Dose Response Curve ◽

Human Origin ◽

Response Curves ◽

Significant Difference ◽

The Mean ◽

Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

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HYPERTROPHIC ADRENALS AND THEIR RESPONSE TO STRESS AFTER LESIONS IN THE MEDIAN EMINENCE OF TOTALLY HYPOPHYSECTOMIZED PIGEONS

Acta Endocrinologica ◽

10.1530/acta.0.0370565 ◽

1961 ◽

Vol 37 (4) ◽

pp. 565-576 ◽

Cited By ~ 19

Author(s):

Richard A. Miller

Keyword(s):

Dose Response ◽

Median Eminence ◽

Response Curve ◽

Liver Parenchyma ◽

Dose Response Curve ◽

Pars Distalis ◽

Adrenal Enlargement ◽

Response To Stress ◽

Lethal Doses ◽

Chromaffin Tissue

ABSTRACT Four per cent formaldehyde, insulin, or epinephrine in oil was injected for 5 days into pigeons subjected to varying degrees of hypophysectomy alone or together with large lesions in the median eminence and hypothalamus. Adrenals atrophied after the removal of the pars distalis alone or together with the neurohypophysis in untreated pigeons but showed markedly hypertrophic interrenal tissue (cortex in mammals) after treatment with formaldehyde or insulin. The slope of the dose-response curve was similar in operated and unoperated pigeons. The accumulation of bile in the liver parenchyma, which may occur after removal of the pars distalis, is an endogenous stress which was associated regularly with adrenal hypertrophy. After very large lesions of the median eminence and ventral hypothalamus in addition to total hypophysectomy, adrenals hypertrophied rather than atrophied, and the response to formaldehyde paralleled that in intact and »hypohysectomized« pigeons. Interrenal tissue was stimulated regularly; chromaffin tissue was partially degranulated, sometimes showed hyperplasia with colchicine, but only occasionally appeared hypertrophied. Epinephrine in nearly lethal doses caused only minimal adrenal enlargement. After adrenal denervation followed by hypophysectomy, the adrenals were still stimulated by formaldehyde. It appears that the interrenal tissue of the pigeon responds to a humoral stimulus not of hypophyseal origin in the absence of the hypophyseal-hypothalamic system.

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ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

Acta Endocrinologica ◽

10.1530/acta.0.042s017 ◽

1963 ◽

Vol 42 (2_Suppl) ◽

pp. S17-S30

Author(s):

Fred A. Kind ◽

Ralph I. Dorfman

Keyword(s):

Dose Response ◽

Active Compound ◽

Subcutaneous Injection ◽

Response Curve ◽

Parent Compound ◽

Dose Response Curve ◽

Relative Potency ◽

Reference Standard ◽

Highly Active ◽

Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

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Treatment of stable angina pectoris. „Mother Courage and her children”

Orvosi Hetilap ◽

10.1556/oh.2008.28317 ◽

2008 ◽

Vol 149 (7) ◽

pp. 291

Author(s):

Viktor Nagy ◽

István Czuriga

Keyword(s):

Angina Pectoris ◽

Stable Angina ◽

Stable Angina Pectoris

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