Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Employing optical density methods, platelet aggregation in response to 1.275, 1.7, and 3.4 micrometer adenosine diphosphate was tested in 46 patients with migraine and 46 controls matched by age, sex, and race. The migraine patients demonstrated platelet hyperaggregability when compared with controls, as manifested by a lower threshold for the platelet-release reaction and increased platelet stickiness following aggregation. There was no correlation of platelet hyperaggregability with the severity of migraine or with the occurrence of migraine-associated neurologic symptoms, suggesting that platelet hyperaggregability is a concomitant feature of the migraine syndrome but not dependent on the occurrence of the actual headache. As platelet hyperaggregability may predispose to development of intravascular platelet aggregates or mural thrombi, the hyperaggregability found here may help explain the increased incidence of stroke and heart attack in migraine patients that has been reported elsewhere.
 ...
PMID:Platelet aggregability in migraine. 56 34

The cerebral vasodilator response induced by topical nitroglycerin and nitroprusside was examined in cats equipped with cranial windows for the observation of the cerebral microcirculation. In cats subjected to chronic unilateral trigeminal ganglionectomy, the vasodilator responses to nitroprusside and nitroglycerin were markedly depressed on the denervated side. Application of a selective calcitonin gene-related peptide (CGRP) antagonist [CGRP(8-37)] on the innervated side reduced the response to nitrodilators to the same extent as seen on the denervated side. The vasodilator response to acetylcholine was unaffected by trigeminal ganglionectomy. CGRP(8-37) almost abolished the vasodilator response to nitroglycerin and sodium nitroprusside and to CGRP, but did not affect the response to adenosine or to adenosine diphosphate. Pretreatment with LY83583, a drug that lowers cyclic GMP levels, diminished the vasodilation to CGRP and to nitroprusside but not to adenosine. We conclude that the nitrovasodilators activate sensory fibers to release CGRP, which in turn relaxes cerebral vascular smooth muscle by activating guanylate cyclase. Hence, nitrovasodilators possess a novel mechanism of action within the cephalic circulation which may explain both the occurrence of vasodilation and headache.
 ...
PMID:Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. 157 43

The investigators conducted a clinical study on antithrombotic effectiveness in ischemic stroke at Siriraj Hospital Medical School, Mahidol University from May 1987 to May 1989. Twenty-nine patients, 16 males and 13 females were enrolled in the study. The ages of the patients ranged from 30-87 years with a mean age of 63 +/- 11 years. Ticlopidine (250 mg) could significantly inhibit platelet aggregation induced by ADP and collagen within 24 hours of drug administration. After 1 week to 6 months, only aggregation by ADP was still inhibited significantly without significant effects on fibrinolytic activity and prostacyclin. Hematocrit was significantly decreased at the 1st and 2nd month of treatment. Serious side effects were skin rash and severe headache while the other common ones were dizziness, and diarrhea but these effects disappeared without discontinuing the drug. Most patients who suffered from nausea, diarrhea and headache, had temporary elevated SGPT. It may be concluded that only half of the recommended dose of ticlopidine has inhibitory effects on both phases of ADP-induced aggregation without interfering with fibrinolytic activity and can maintain prostacyclin. However, it also possesses either serious or common side-effects. This drug, therefore, should be used with the awareness of the clinician.
 ...
PMID:Clinical study on antithrombotic effects of ticlopidine in ischemic stroke. 174 38

Platelet aggregation induced by ADP, collagen and platelet-activating factor was studied in common (migraine without aura) and classical migraine (migraine with aura) patients during and between attacks. The EC50* values for ADP and platelet-activating factor were significantly higher, whilst that for collagen was significantly lower in classical migraine patients during headache-free intervals compared to healthy volunteers. The EC50 values obtained for common migraine sufferers during symptom-free periods were similar to those of controls. During attacks, the EC50 value for ADP, but not for collagen and platelet-activating factor, was significantly higher than that of the controls. In healthy subjects a positive correlation was found between ADP and collagen-induced aggregation. In contrast, there was a U-shaped correlation matrix in classical migraine patients. The present observations show that platelet aggregation is altered in migraine patients and this raises the possibility that platelet-activating factor may be involved in the pathogenesis of migraine.
Cephalalgia 1990 Aug
PMID:Platelet aggregation of migraineurs during and between attacks. 224 63

To assess efficacy and side effects during chronic oral therapy, we studied the effect of ketanserin (Kn) in 17 hypertensive patients for a period up to 1 year. Ketanserin controlled blood pressure satisfactorily in 25%, in part in 50% and had little or no effect in 25%. Reduction in diastolic pressure equalled that in systolic pressure at rest and after exercise and during handgrip. Pulse rate was slowed. Dosage in excess of 60 mg of Kn per day caused troublesome central nervous system symptoms or headache in some patients. A nonsteroidal antiinflammatory drug appeared to antagonize the antihypertensive effect of Kn in one patient. Red cell rigidity and platelet aggregation to ADP and collagen were significantly decreased. Serum potassium and uric acid were significantly decreased; serum creatinine increased during Kn treatment. The antihypertensive and pulse slowing effects of Kn were confirmed during the year's study, in a randomized placebo-controlled crossover study.
 ...
PMID:Clinical studies with ketanserin in hypertension. 241 40

Plasma levels of the prostacyclin analogue, iloprost, were measured by antibody/GC/MS in healthy male volunteers given 1 and 3 ng/kg per min i.v. for 45 min, and 1 microgram/kg p.o. Following i.v. infusion, the steady-state plasma levels of iloprost were strictly dose-dependent (46 +/- 8 pg/ml and 135 +/- 24 pg/ml). The disposition was biphasic with half-lives of 3-4 min and 0.5 h. After oral administration, absorption of the drug was extremely rapid, the maximum plasma level of 251 +/- 32 pg/ml being achieved after 10 +/- 6 min. The bioavailability was 16 +/- 4%. Platelet aggregation induced by 2 microM ADP was reduced by 53% and 68% at the end of the two different infusions, and by 68% 15 min after p.o. administration. The ex-vivo inhibition of platelet aggregation by iloprost was not affected by preceding drug treatment. The cAMP content of platelets was increased by a factor of 2.5 at the end of the infusions and to a lesser extent 15 min after oral dosing. A slight increase in heart rate occurred during the infusion and within 30 min after oral administration; blood pressure was virtually unaffected. Except for transient side-effects (facial flush and headache) no adverse reactions were observed.
 ...
PMID:Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man. 242 42

The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng X kg-1 X min-1 for 4 h and oral administration of 0.1 and 0.48 microgram/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml X min-1 X kg-1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min, respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 microgram/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolites were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor- and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduced by 60% during the i.v. infusion and 15 min after oral administration of 0.48 microgram/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.
 ...
PMID:Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers. 244 64

Safety, tolerance, and pharmacology of 9-beta-methylcarbacyclin calcium (ciprostene calcium) was investigated in healthy male volunteers. This stable prostacyclin analogue was infused intravenously into groups of 12, 11, and three volunteers for three, six, and eight hours, respectively, in doses up to 480 ng/kg/min. Based on the tolerance data obtained, a single-blind, placebo-controlled study was conducted. Seven subjects were infused for 8 hr/d for three days with ciprostene at a maximum dose of 160 ng/kg/min and seven subjects received placebo. One subject from each group did not complete the infusion schedule, and they were not included in the final analysis. During infusion of ciprostene, consistent changes in blood pressure and heart rate did not occur. Most frequent adverse drug reactions consisted of headache, restlessness, nausea, perspiration, flushing, and jaw pain. As compared with placebo, ADP-induced platelet aggregation was inhibited during the infusion period (P = .048). Significant (P = .04) elevations of platelet cyclic AMP were observed in subjects during infusion of ciprostene. Pre- versus postinfusion routine laboratory evaluations, fibrinogen concentration, antiplasmin activity, and plasminogen and template bleeding times remained unchanged. Placebo- and drug-treated subjects had a daily postinfusion shortening of euglobulin clot lysis time (ECLT). The preinfusion minus postinfusion ECLT for ciprostene subjects on days 2 and 3 (133 and 118 min, respectively) compared with placebo (239 and 217 min) suggest a trend to increased fibrinolytic activity. Based on the outcome of this trial, it is estimated that ciprostene is about 15 times less potent than prostacyclin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tolerance and pharmacology of ciprostene, a stable epoprostenol (prostacyclin) analogue in humans. 300 77

Sixteen patients who presented under the age of 40 years with amaurosis fugax have been studied. Follow up from the time of presentation was one to 13 years with a median of 3 years. One patient whose attacks of uniocular visual loss were associated with headache developed a permanent uniocular field defect. None of the other patients has suffered permanent visual loss, or had symptoms of cerebral or myocardial ischaemia. All angiograms were normal and it is suggested that carotid angiography is unnecessary in this age group. Four out of ten patients studied demonstrated evidence of platelet hyperaggregability to low concentrations of arachidonic acid and adenosine diphosphate with spontaneous aggregation. However, in six patients treated with aspirin, including three with previous platelet hyperaggregability, there was no change in the frequency of their attacks implying that the observed platelet abnormalities were not the cause of the amaurosis fugax.
 ...
PMID:Amaurosis fugax under the age of 40 years. 310 96

In fourteen untreated migraine patients with a mean age of 40 years platelet sensitivity to 5HT, EN and ADP was investigated during the prodromal phase (three patients), 12-48 h after headache (three patients) and during the headache-free period (eight patients). Platelet sensitivity was tested using an optical density method and was calculated by the percentage of disaggregation (%DA) occurring 3 min after the peak aggregation. Platelet release reaction was assessed using beta-thromboglobulin (beta-TG) as an indicator. Platelet sensitivity to low concentrations of 5HT, EN and ADP (0.3 X 10(-9) M/ml) was most marked during the headache and prodromal phases. The least platelet sensitivity in migraineurs was detected during the headache-free interval, but was still higher than in the control group. beta-TG levels were increased during the headache phase indicating platelet release reaction. A general hyperaggregability of platelets in migraineurs has been demonstrated and in addition a varying sensibility of platelets to low concentrations of 5HT, EN and ADP has been established.
Cephalalgia 1985 May
PMID:Evidence of enhanced platelet aggregation and platelet sensitivity in migraine patients. 316 Apr 75


1 2 3 4 5 Next >>