Lysine clonixinate in the treatment of primary dysmenorrhea.

The efficacy and tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle, rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post- and menstrual periods; possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptoms. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24, 24/24 and only 2 out of the 24 patients, respectively. Concomitant symptoms consisted in headache (12), mastalgia (14) and discomfort (12). Results were obtained by averaging the data from the treatment periods with each drug. Menstrual pain was reduced from 2.9 +/- 0.7 to 1.9 +/- 0.7 with P administration and to 0.66 +/- 0.4 with the administration of LC, a highly significant difference between treatments (p < 0.0001). Premenstrual pain was reduced nonsignificantly from 0.79% to 0.58% with P administration and significantly to 0.29% with administration of LC (p < 0.001). Intramenstrual pain affecting all patients at baseline was reduced significantly by 9% with P and also significantly by 50% with LC (p < 0.001). No differences were encountered in concomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p < 0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.

Lysine clonixinate in the treatment of primary dysmenorrhea

The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.

Lysine clonixinate in the treatment of primary dysmenorrhea

The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported. (AU)

Picogram detection of eicosanoids by ultraviolet absorbance after narrow-bore high-performance liquid chromatography. Comparison with conventional-bore column.

Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase high-performance liquid chromatography of eleven eicosanoids. Separation and quantitation by ultraviolet absorbance at 190 nm using conventional-bore ODS columns were compared. Using the improved sensitivity obtained by means of the narrow-bore column, i.e. 250-pg detection limits of a standard solution, analysis of eicosanoids in kidney medulla was achieved. Parallel quantitation by radioactivity, using [1-(14)C]arachidonic acid as substrate, was applied.

Estrogens induce lipoxygenase derivative formation in rabbit lens.

The effect of estrogens on arachidonic acid metabolism was studied in lenses from normal and sex hormone-treated female rabbits. Analysis of the metabolites derived from incubation of these lenses with (1-14C) arachidonic acid provides the first evidence that estradiol activates the lipoxygenase pathway, as indicated by 5-S-hydroxy-6,8,11,14-eicosatetraenoic acid--like product formation, an effect that can be prevented by progestin treatment. Prostaglandin synthesis was not demonstrated by the control or estrogen-treated rabbit lenses, suggesting that lipoxygenase is the major arachidonic acid pathway in the lens.

Pressor effects of indomethacin in two anephric patients with chronic hypotension.

Two anephric patients with chronic hypotension were treated with indomethacin (150 mg/day). Indomethacin increased supine blood pressures from 63 +/- 4/37 +/- 3 mm Hg (mean +/- SD) to 76 +/- 5/48 +/- 6 mm Hg (patient 1) and 93 +/- 6/47 +/- 6 mm Hg to 112 +/- 8/61 +/- 5 mm Hg (patient 2), P less than .01. Similar changes occurred in standing pressures. The increases in pressures were associated with decreases in blood concentrations of prostaglandins 6-keto-F1 alpha, E2, and F2 alpha, measured by radioimmunoassay. These results suggest that indomethacin may raise blood pressure in certain anephric patients by inhibiting synthesis of extra-renal, vasoactive prostaglandins. Indomethacin may be useful in the treatment of chronic hypotension in anephric patients.

Phospholipase C activity in rat kidney. Effect of deoxycholate on phosphatidylinositol turnover.

Rat renal cortical and medullary slices incorporate [14C]arachidonate into phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and triacylglycerols. The percent distribution of [14C]arachidonate among the various phospholipids is similar in renal cortex and medulla, although the total amount of radioactively labeled phospholipids is higher in the renal medulla. Subsequent incubation of prelabeled slices in the presence of deoxycholate induces a loss of radioactivity from [14C]phosphatidylinositol, with a concomitant increase in 1,2-[14C]diacylglycerol. Neutral lipids are not affected. The degradation of phosphatidylinositol to [14C]diacylglycerol indicates the presence of phospholipase C activity. Renal medulla seems to be more sensitive to deoxycholate than the renal cortex. Deoxycholate also induces slightly the disappearance of some 14C radioactivity from phosphatidylethanolamine and phosphatidylcholine, which might reflect activation of phospholipase A2. The activity of the phospholipase C could constitute the first step in the sequence of reactions that leads to the release of arachidonic acid.

High performance liquid chromatography and UV detection for the separation and quantitation of prostaglandins.

A fast and reliable method for the separation and quantitation of arachidonic acid metabolites PGF1 alpha, PGF2 alpha, PGD2, PGE1, PGE2, PGB2, PGA2, 6-keto PGE1, 6-keto PGF1 alpha, TxB2 and 15-keto PGE2 by high-performance liquid chromatography has been developed. Utilizing a single reverse-phase column and a UV spectrophotometer, sensitivity as little as 30 nanograms of each of these prostaglandins can be separated and subsequently detected. Although this study was performed using standards, it is highly promising for future application to biological fluids.

Prostaglandin metabolism in the fetal and maternal vasculature.

The capacity of fetal and maternal blood vessels to synthesize the antithrombotic vasodilator agent prostacyclin (PGI2) suggests that this substance participates in the circulatory adjustments to pregnancy. We studied the capacity of fetal and maternal blood vessels to metabolize [1(-14)C]arachidonic acid; thin-layer chromatography was used to separate PGE2, PGF2alpha, and 6-keto-PGF1alpha (the stable hydrolysis product of PGI2), and these were then quantitated by scintillation counting. Fetal vascular tissues (aorta, ductus arteriosus, and pulmonary arteries) generated tenfold more PGI2 than PGE2. Prostacyclin accounted for more than 50% of the prostaglandins synthesized by fetal blood vessel measured by recovery of its hydrolysis product, 6-keto-PGF1alpha. In contrast, in the mature animals, the aorta and pulmonary artery generated less PGI2 than did fetal tissue, whereas the mesenteric arteries exhibited high biosynthetic capacity comparable to that of the fetal vasculature. Release of prostaglandins by the umbilical blood vessels and ductus arteriosus was also measured by mass fragmentography. The identity of 6-keto-PGF1alpha was confirmed by mass spectroscopy. The high and almost identical capacity of all fetal blood vessels, except the umbilical arteries and veins, to synthesize PIG2 could reflect an important role for this prostaglandin in the regulation of the fetal circulation.

Endogenous prostaglandin synthesis inhibitor in the renal cortex. Effects on production of prostacyclin by renal blood vessels.

1. The capacity of various tissues of the porcine kidney to convert [1-14C]arachidonic acid into radiolabelled prostaglandins was studied. 2. Only after removal from the cortical matrix, were renal blood vessels able to convert arachidonic acid into prostaglandins (primarily prostacyclin). In contrast, convoluted tubules showed a low capacity to metabolize arachidonic acid. 3. The failure to demonstrate prostaglandin synthesis by renal cortical slices is related to the presence of an inhibitor of cyclo-oxygenase. Thus the addition of renal cortical incubate to isolated vascular tissues and ram seminal vesicles inhibited their ability to synthesize prostaglandins. 4. Slices of renal medulla metabolized arachidonic acid primarily to prostaglandin F2alpha; lesser amounts of prostaglandin E2 and prostacyclin were generated. 5. The large capacity of the renal vasculature to generate prostacyclin is consistent with an important role for this prostaglandin in regulation of renin release and renal haemodynamics.

Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus.

Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro. After incubation of slices of ductus arteriosus in Krebs' solution with (1-14C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguishable from 6 keto-PGF1alpha as determined by its chromatographic motility and resistance to alkaline conversion to PGB. The PGI2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF1alpha, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.

Role of naturally occurring vasoactive principles in hypertension. State of the art.

Hypertension may result from excessive activity of one or more components of the blood pressure-elevating system. These include the adrenergic nervous system, the renin-angiotensin axis, and mineralocorticoids (aldosterone), which potentiate each other, reinforcing their effects on renal hemodynamics and electrolyte transport and thereby affecting extracellular fluid volume, vascular tone, and reactivity. We consider of no less importance in the genesis of hypertension the failure of one or more components of the blood pressure-lowering system: the kallikrein-kinin system, prostaglandin, or one or more lipids associated with the renomedullary interstitial cells. As a corollary of this hypothesis, if one assumes tonic activity of these opposing blood pressure-regulating systems, in the case of a deficiency of the vasodepressor system, hypertension should result. That is, unopposed activity of the pressor system should be sufficient to increase blood pressure without an increase in the "basal level" of its activity. Hypertension, then, may be considered to result from either uncompensated deficiencies or excesses, which may be relative or absolute, of one or more components of the vasodepressor and vasopressor systems.

Comparison of colposcopy directed biopsies and cold knife conization in patients with abnormal cytology.

One hundred patients with abnormal cytology were evaluated by colposcopy, and histologic material was obtained by directed biopsies, cold knife conization and endocervical curettage. The colposcopy directed biopsies provided the diagnosis in 94 per cent of the patients, and the colposcopic impression was accurate in 89 per cent of the patients. Cold knife conization was performed in 98 patients, since two patients had invasive carcinoma on colposcopic directed biopsy. In 75 patients, the histopathologic finding on cone biopsy was in complete agreement with the directed biopsies. In 11 patients, the directed biopsies were a degree higher than on cone biopsy, and in six patients the histopathologic findings were a degree lower. In six patients the colposcopic directed biopsies missed the diagnosis of dysplasia. No patients with carcinoma in situ or invasive carcinoma were missed by the colposcopic directed biopsies.