Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two models of experimental colitis, an effect that is not due only to its vasoconstrictor properties. Modulation of NO generation may be a novel therapeutic approach in inflammatory bowel disease.
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PMID:Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. 867 8

Enhanced levels of soluble TNF-receptors (sTNF-R) have been reported in patients with chronic renal failure. The aim of the present study was to evaluate the effects on sTNF-R levels in plasma of haemodialysis patients of the anticoagulation method and of the type of membrane used, as well as the variability of predialysis sTNF-R levels during time. All haemodialysis patients tested (n = 35) showed increased levels of both sTNF-R55 (72.4 +/- 5.7 ng/ml, P < 0.001) and sTNF-R75 (18.2 +/- 2 ng/ml, P < 0.001) before dialysis, as compared with normal healthy controls (< 2.5 ng/ml for both sTNF-R), confirming previous observations. sTNF-R levels were determined before and during haemodialysis at different time intervals in patients receiving either heparin (2500 U, 5000 U, or 10,000 U), low molecular weight heparin, or periodic saline flushing to prevent coagulation of the extracorporal circuit. A transient, small decrease in both sTNF-R levels occurred at the beginning of haemodialysis (t = 15 min) with all anticoagulation methods used. At the end of haemodialysis, sTNF-R55 and sTNF-R75 concentrations were only minimally affected (P > 0.05). Predialysis sTNF-R levels were similar in patients dialysed on either cellulose diacetate or polyacrylonitrile. Finally, there were only minimal variations in predialysis sTNF-R levels in individual patients during the 1 week observation period. Although the biological consequences of the increased TNF-binding ability of serum from haemodialysis patients is still unclear, it could play a role in the complex immunological perturbations of uraemic patients.
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PMID:Increased plasma levels of soluble tumor necrosis factor-receptors in uraemic patients: effects of dialysis, type of membrane, and anticoagulation method. 780 Feb 12

Recently, murine peritoneal exudate polymorphonuclear leucocytes (PMNs) have been proved to secrete complement C3. In this report we show the secretion of C3 by normal human blood PMNs. ELISA assay was used to detect secreted C3 in culture supernatants of PMNs, while immunoperoxidase staining was used for intracellular C3 detection. 12-o-tetradecanoyl phorbol 13 acetate (TPA) had a flushing effect on C3 secretion by PMNs but not macrophages, suggesting a special C3 storing capability in PMNs. Dioctanoyl glycerol, mezerein and calcium ionophore A23187 caused the same marked increase in C3 secretion by PMNs. This suggests the contribution of protein kinase C and the calmodulin pathway in the mechanism of C3 secretion, similar to murine peritoneal exudate PMNs. In some cases of systemic lupus erythematosus, C3 secretion by blood PMNs was increased but no similar response to TPA could be detected.
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PMID:The secretion of the third component of complement (C3) by human polymorphonuclear leucocytes from both normal and systemic lupus erythematosus cases. 841 68

A simple device which releases chlorhexidine acetate into dental unit water supplies is described. The device comprised methyl methacrylate resin containing 40% by weight of chlorhexidine powder, cast into a rod shape and placed in a reservoir. After initial cleaning by flushing with hypochlorite, five dental units were fitted with the device and five units acted as controls. The device successfully kept four units virtually free of bacteria over a 3-month period but effective cleaning of the tubing within the units was found to be essential for success. Sustained release of chlorhexidine offers one means of tackling the problem of contaminated water in dental units, without resorting to complex pumping or metering systems.
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PMID:Control of bacteria in dental water supplies. 846 Nov 99

Amlodipine belongs to the dihydropyridine class of calcium channel blockers. Both short and long term studies indicate that amlodipine effectively lowers mild to moderately elevated blood pressure and relieves symptoms of angina pectoris. In comparative studies, its antihypertensive efficacy is similar to that of other established agents such as beta-blockers, diuretics, ACE inhibitors and other calcium channel blockers (including the dihydropyridines); limited comparative data are, however, available in patients with angina pectoris. Amlodipine may offer potential in patients with congestive heart failure. Vasodilator adverse events such as oedema, headaches, and flushing are commonly observed with amlodipine. The drug does not appear to cause postural hypotension, reflex tachycardia or cardiac conduction disturbances. Comparative studies suggest that amlodipine is at least as well tolerated as other standard agents. Thus, amlodipine provides an attractive therapeutic option for the treatment of hypertension, and offers potential for patients with angina pectoris. Its beneficial effects in patients with congestive heart failure require confirmation in future studies.
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PMID:Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. 852 73

Postmenopausal women experiencing hot flashes in whom estrogen replacement is contraindicated have alternatives available to them; however, there is no clearly defined treatment modality. The literature addressing many of these alternatives has serious limitations, which include the small number of women enrolled and lack of comparative studies between agents. Each patient needs to be assessed in terms of her current medical status, concomitant medications, and the degree to which vasomotor instability interferes with everyday activities. The literature suggests that megestrol acetate 20 mg bid may provide significant relief. Women who opt to use megestrol acetate must be told in advance that the effects will not be felt immediately particularly if tamoxifen is used concomitantly. Clonidine and medroxyprogesterone may constitute potential alternatives, but patients may not be able to tolerate the adverse effects. Because of the lack of literature supporting their clinical use, options such as vitamin E and ginseng need to be approached cautiously. Exercise has a role in alleviating some of the complications associated with menopause, such as heart disease and osteoporosis, but its effect on neurotransmitters and hormone concentrations, and how this relates to the treatment of hot flashes have not been characterized. Patients should be told that regular physical activity, a balanced diet, avoidance of alcohol and caffeine, and stress reduction may be of additional help in decreasing vasomotor flushing.
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PMID:Alternatives to estrogen for the treatment of hot flashes. 922 57

To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.
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PMID:Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension. 949 99

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects.
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PMID:Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. 959 22

Thirty postmenopausal women were randomized to receive either continuous combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women) and were monitored to determine the relationship between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregular bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy were measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and endometrial flushing. The levels of PP14 in uterine flushings were significantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentrations of PP14 found in flushings after ccHRT were considerably greater than those found in flushings after tibolone; levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concentration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plasma and uterine CA125 were unchanged by either treatment. Histological analysis of the endometrium from women after 12 months of HRT treatment showed that 86% (6/7) of women on ccHRT had secretory activity as compared to 44% (4/9) women on tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were more likely to have irregular bleeding (P < 0.05). Our studies have shown that endometrial PP14 but not CA125 concentrations are raised to a significant degree by two different forms of period-free HRT regimens. Increased PP14 concentrations in uterine flushing may suggest endometrial stimulation of some form and predict the predilection to irregular bleeding. Thus uterine PP14 concentrations may be used to monitor endometrial responses in women on HRT.
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PMID:A prospective randomized controlled study comparing the morphological and biochemical responses of the endometrium to two different forms of 'period-free' hormone replacement therapy. 975 7

A GnRH antagonist (Antarelix) treatment was used during the breeding season of Romanov ewes, to investigate whether LH pulses are required the day before the preovulatory surge for normal early embryo development in vivo (Expt 1) and in vitro (Expt 2). In Expt 1, at the onset of oestrus after removal of a fluorogestone acetate sponge, group A0.5 (n = 22) received a subcutaneous injection of 0.5 mg Antarelix, and ovulation was induced with an intravenous injection of 3 mg pig LH 24 h later. The control group (group C, n = 20) were untreated. All ewes were mated naturally at 36 and 48 h after oestrus and embryos were recovered 8 days after sponge removal. There were significant differences in the decrease in LH and in the increase in FSH concentration after Antarelix treatment between treated and control groups. The ovulation rate and embryo recovery rate were not significantly different between the two groups but the blastocyst rate was lower (P < 0.0001) in group A0.5 than in group C, with more unfertilized or degenerated oocytes in group A0.5 (69.2%). In Expt 2, 24 h after sponge removal, group A (n = 10) and group B (n = 10) received one subcutaneous injection of 0.5 mg Antarelix. The control group (group C, n = 10) was left untreated. LH pulsatility was re-established in group B with hourly intravenous injections of 5 micrograms ovine LH for 24 h. Oocytes were collected by flushing the oviducts 28 h after the LH surge, and were fertilized and cultured in vitro for 7 days. Ovulation and cleavage rates were not significantly different among the three groups but a higher rate of blastocysts (P < 0.01) was obtained after Antarelix treatment when LH pulsatility was re-established (group B). Oestradiol concentration was strongly depressed (P < 0.0003) after Antarelix treatment in group A, but was maintained after injection of LH pulses in group B, although at a lower value than before the preovulatory surge in the control group. In conclusion, inhibition of endogenous LH pulses 1 day before the preovulatory surge was not essential for ovulation and in vitro fertilization but was associated with a decrease in plasma oestradiol concentrations and inferior embryo development both in vivo and in vitro. When LH pulsatility was re-established, oestradiol concentrations increased and embryo development was restored.
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PMID:Reduction of the developmental competence of sheep oocytes by inhibition of LH pulses during the follicular phase with a GnRH antagonist. 1064 47


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