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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. PGD2 (DP)-receptors mediate inhibition of platelet aggregation and vasodilatation. If receptor reserve were greater on platelets it might be possible to separate these effects. To determine whether such a difference in receptor reserve exists, we have examined the effects of a highly selective DP-receptor partial agonist 192C86 on platelet aggregation and the cardiovascular system in healthy volunteers. 2. Using an open, dose-escalating study design, four male volunteers received constant rate intravenous infusions of 192C86 for up to 60 min. Ex vivo platelet aggregation to ADP and collagen in platelet-rich plasma (PRP) and whole blood (WB) was studied at baseline, after 15, 30 and 60 min of each infusion and at 180 min post-infusion. Heart rate (HR), systolic and diastolic (DBP) blood pressure were measured at frequent intervals. Adverse experiences were monitored by checklist. Facial flushing was assessed by the volunteer using a visual analogue scale, by an observer using a numerical scale and by full-face colour photographs. Blood was taken for assay of plasma 192C86 concentrations by radio-immunoassay (r.i.a.). 3. 192C86 (0.007-0.058 micrograms kg-1 min-1) inhibited platelet aggregation to ADP and collagen both in PRP and WB in a dose-dependent manner. However, this was always accompanied by a decrease in DBP, increase in HR and facial flushing. Plasma concentrations of 192C86 were at or below the limits of sensitivity of the r.i.a. (0.5 ng ml-1). 4. The highest infusion rate was stopped after 20 min due to symptomatic hypotension on standing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of a prostaglandin DP-receptor partial agonist (192C86) on platelet aggregation and the cardiovascular system in healthy volunteers. 145 68

Many general signs familiar to physicians can be found on the skin in cardiac patients. These include (a) cyanosis, central and peripheral, (b) erythremia, flushing and erythema, (c) digital clubbing and (d) alteration in texture. Specific cardiac conditions often have useful diagnostic cutaneous clues. Of these the association of coronary heart disease, hyperlipidemia and xanthomas is the most important. Rare syndromes such as the "leopard syndrome" often have distinctive skin signs. Multisystemic disorders may affect the heart and skin simultaneously or in sequence. They include collagen vascular diseases, amyloidosis, sarcoidosis and relapsing polychondritis. Finally iatrogenic disease arising from treatment of cardiac or cutaneous disease may induce changes in one or the other organ. The heart and the skin have much in common. These manifestations help elucidate the cause, evaluate the diagnosis, and follow the treatment and progress of these diseases.
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PMID:Cutaneous manifestations of cardiac diseases. 225 49

Using newborn rat calvaria, we determined the effects of oxygen tension on bone cell metabolism in vitro. Halved calvaria were incubated in medium either in air or after flushing nitrogen or oxygen and studied for collagen synthesis, calcium uptake, and DNA content. The percentages of DNA content, radioactive proline count in mg of bone tissue, and radioactive proline count combined with counts of medium and bone tissue in the nitrogen-exposed group were less than those of their pair-matched controls. Percent calcium counts per DNA and calcium uptake per mg of tissue were greater in the nitrogen-exposed group than in the pair-matched controls. In contrast, no difference was found in any measurements in the oxygen-exposed group compared with controls. It is concluded that collagen synthesis, in contrast to proline uptake, is not affected by low oxygen, whereas calcium uptake is greatly enhanced. Furthermore, low oxygen tension exerts a greater effect on bone cell metabolism than does the hyperoxic condition.
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PMID:The effect of oxygen tension on collagen synthesis and calcium uptake in newborn rats' calvaria in vitro. 231 96

Forty-six elderly patients (mean age 60 years) suffering from diabetes mellitus (DM), or essential or arteriosclerotic hypertension (HT) were divided into 4 groups. Group 1 served as a control, group 2 was administered 1500 mg niceritrol, group 3 was administered 162 mg acetylsalicylic acid (ASA), and group 4 was administered both 1500 mg niceritrol and 162 mg ASA/day for 8 weeks. Niceritrol lowered serum levels of beta-lipoprotein and total cholesterol and increased HDL cholesterol, usually in 8 weeks. ASA did not affect the lipid-lowering effects of niceritrol. Platelet aggregation induced by epinephrine (1 microgram/ml), collagen (1 microgram/ml), and ADP (2 microM) was depressed in groups 2, 3 and 4. Degrees of depression were higher in groups administered ASA (groups 3 and 4) than in the group administered niceritrol alone (group 2). Plasma fibrinogen levels were lowered in groups administered niceritrol (groups 2 and 4) in 8 weeks. Apparent whole blood viscosity measured at shear rates of 37.6/s and 376/s was improved only in group 4 in 8 weeks, while hematocrit did not change during the study. Because flushing, the most frequent side effect of niceritrol, can be easily controlled by a low dose of ASA, and because the combination of the 2 drugs has some beneficial effects on blood rheology, this combination is considered worthwhile for treatment and prevention of atherosclerosis.
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PMID:The effects on lipids, blood viscosity and platelet aggregation of combined use of niceritrol (Perycit) and a low dose of acetylsalicylic acid. 400 83

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
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PMID:A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. 608 4

Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.
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PMID:The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. 620 61

Following an open pilot study, BW 245C , a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms BW 245C produced significant (p less than 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C . Platelet aggregation responses to ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms BW 245C . Aggregation responses to collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms BW 245C and also at 120 minutes after 50 micrograms BW 245C . Bleeding time was unchanged in response to either dose of BW 245C . There was no change in headache or abdominal discomfort scores following either dose of BW 245C . Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.
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PMID:Effects of single oral dose administration of a hydantoin prostaglandin analogue BW 245C in man. 672 64

We report the case of a 41-year-old man infected with human immunodeficiency virus who had two episodes of aseptic meningitis that occurred 2 weeks apart; the first was associated with ingestion of trimethoprim-sulfamethoxazole (TMP-SMZ) and the second was associated with ingestion of TMP alone. Onset of fever, headache, and flushing was abrupt, followed by somnolence, hearing loss, and aphasia. Analysis of the CSF showed pleocytosis and an elevated protein level. The findings resolved within 48 hours after withdrawal of the drug. We also review 18 previously reported cases of TMP-SMZ- or TMP-induced meningitis, 17 of which occurred in women. In all of these cases, a similar abrupt onset and resolution were noted. Six of the 18 patients had collagen-vascular diseases. All but two of these patients had multiple recurrent episodes of meningitis before the diagnosis was made. We conclude that the diagnosis of TMP-SMZ- or TMP-induced meningitis should be considered when a patient receiving these drugs has recurrent episodes of aseptic meningitis.
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PMID:Trimethoprim-induced aseptic meningitis in a patient with AIDS: case report and review. 781 61

Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization.
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PMID:Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation. 847 58

Damage to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation, and is believed to be responsible for the wrinkled appearance of sun-exposed skin. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).
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PMID:Molecular basis of sun-induced premature skin ageing and retinoid antagonism. 855 87


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