New ethacridine derivatives as the potential antifungal and antibacterial preparations.

Until the 20th century fungal infections were rather easy cured, and the need of new antifungal drugs was low. However, low choice of antifungal preparations, their toxicity, limited spectrum of action, and ability to produce resistant strains show the need of new effective medicines for systemic fungal diseases in nowadays. Our goal of research was to synthesize new antimicrobial compounds containing three or more pharmacophores in one molecule. The initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S-demethylation to yield 2-amino-substituted thiazolidinones. Ethacridine, nitrofuran aldehydes and nitrobenzene aldehyde as pharmacophoric amino or aldehyde group having compounds have been used. Antimicrobial (antifungal) activity of the new compounds was screened in vitro in these bacterial cultures: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 33499 and fungal cultures: Candida albicans ATCC 60193, Candida glabrata, Candida krusei, Candida kefyr ATCC 8614, Candida tropicalis ATCC 8302, Candida parapsilosis. Results showed that the new compounds were significantly more effective as antimicrobial agents than initial preparation ethacridine. Ethacridine derivatives were not only effective against numerous gram-positive and some gram-negative bacteria, but the spectrum of action has been discovered against fungi. Minimal fungistatic concentration varies in the range 10.0-750 microg/mL and antibacterial concentration is in the range 62.5-1000 microg/mL. Compound 2a having nitrofuryl substituent in the fifth position of tiazolidine cycle was the most active of synthesized ethacridine compounds. The obtained results gave the opportunity to separate the perspective group of potential antiinfective compounds.

Isolation of plasminogen activator inhibitor-2 (PAI-2) from human placenta. Evidence for vitronectin/PAI-2 complexes in human placenta extract.

Plasminogen activator inhibitor-2 (PAI-2), found in human placenta and pregnancy plasma, was prepared in a highly purified and functionally active form from human placenta. The purification was achieved by a combination of Rivanol and ammonium sulfate precipitation, followed by chromatography on DEAE Affigel Blue, hydroxylapatite and phenylalanine-Sepharose. PAI-2, which is precipitated by low Rivanol concentrations, can be selectively redissolved from the pellet by increasing the Rivanol concentration in the presence of a reducing agent, i.e. dithiothreitol. The purified protein shows a molecular mass of 45 kDa in SDS PAGE, cross-reacts with monoclonal antibodies against PAI-2 (Mab'PAI-2), and inhibits the amidolytic activity of urokinase-type plasminogen activator (u-PA) towards the chromogenic substrate Glu-Gly-Arg-pNA (S-2444). The specific activity of the purified inhibitor was 52,300 units/mg, attaining 71,000 units/mg in peak fractions. In the immunopurification of placental extract on anti-PAI-2 Sepharose, the eluate showed the expected reaction with Mab' PAI-2, and it also cross-reacted with anti-vitronectin serum. In order to complement these results, anti-vitronectin Sepharose was used for immunopurification of placenta extract. In Western Blot experiments the eluates of anti PAI-2 Sepharose and anti-vitronectin Sepharose both showed a heterogeneous pattern of high molecular weight bands recognized by either polyclonal antiserum against vitronectin or Mab'PAI-2. In either case, reduction of the eluates releases mainly a 45-kDa band, which is recognized by Mab'PAI-2, or 80-kDa and 76-kDa bands recognized by anti-serum against vitronectin. These data suggest that the predominant form of PAI-2 in placenta extract is heterogeneous and of high molecular mass, containing complexes in which vitronectin is covalently bound to PAI-2 by disulfide bridges.

Second trimester pregnancy termination using extra-amniotic ethacridine lactate.

OBJECTIVE: To investigate the efficacy of ethacridine lactate by the extra-amniotic route for second trimester pregnancy termination and its associated complications. DESIGN: Retrospective study of women undergoing second trimester termination, over 3 1/2 years, with extra-amniotic ethacridine alone, or extra-amniotic ethacridine supplemented later by extra-amniotic 15-methyl prostaglandin F2 alpha. SETTING: Teaching hospital in Bombay. PATIENTS: 315 consecutive women undergoing late abortions with extra-amniotic ethacridine. Demographic features were similar in the two groups. INTERVENTIONS: In group 1, 207 women had 150 ml of 0.1% ethacridine lactate injected slowly into the extra-amniotic space. In group 2, 108 women had the initial injection supplemented 6 h later by an extra-amniotic injection of 250 micrograms (1 ml) of 15-methyl prostaglandin F2 alpha. MAIN OUTCOME MEASURES: The occurrence of abortion following the induction procedure. The development of complications such as haemorrhage, infection, or injury to the uterus or cervix. RESULTS: The method was successful in 191 women (92%) in group 1 and in 106 (98%) in group 2. The median induction-abortion intervals were 35 and 19 h, respectively (Mann-Whitney U test, P less than 0.001). The corrected complication rate was less than 10% (30 women), with unplanned uterine evacuation in 6% (20), haemorrhage in 1% (4), and pelvic infection in 4% (14). CONCLUSION: The use of extra-amniotic ethacridine lactate provides an effective and safe treatment method for second trimester legal abortion. The induction-abortion interval can be appreciably reduced by supplementary prostaglandin.

PIP: This study investigated the efficacy of ethacridine lactate by the extraamniotic route during 2nd trimester pregnancy termination as well as its associated complications. This retrospective study of 315 women undergoing 2nd trimester terminations over a 3 1/2 year period was based at a teaching hospital in Bombay. Patients received either extraamniotic ethacridine alone or supplemented later with extraamniotic 15-methyl- prostaglandin F2alpha (PGF2alpha). Women were divided into 2 groups--in group 1, 207 women received 150 ml of 0.1% ethacridine lactate injected slowly into the extraamniotic space; in group 2, 108 women had the initial injection supplemented 6 hours later by an extraamniotic injection of 250 mcg (1 ml) of 15-methyl-PGF2alpha. Outcome measures which were evaluated were the occurrence of abortion following the induction procedure and the development of complications such as hemorrhage, infection, and injury to the cervix or uterus. The method was successful in 191 women (92%) in group 1 and in 106 (98%) in group 2. The mean induction-abortion intervals were 35 and 19 hours, respectively (Mann-Whitney U test, p0.001). The corrected complication rate was 10% (30 women), with unplanned uterine evacuation in 6% (20), hemorrhage in 1% (4), and pelvic infection in 4% (14). The authors conclude that the use of extraamniotic ethacridine lactate provides an effective and safe treatment method for 2nd trimester legal abortion. The induction-abortion interval can be appreciably reduced by supplementary PGs.

Induction of second trimester abortion by intraamniotic instillation of Rivanol (ethacridine) combined with oxytocin infusion.

We report our experience of 0.1% intraamniotic Rivanol in the interruption of 100 midtrimester pregnancies (15-24 gestation weeks). The mean injection to abortion interval was 37.2h and there were no complications. Intraamniotic Rivanol injection combined with oxytocin infusion seemed an effective and safe method for terminating second trimester pregnancies.

[Intra-amniotic Rivanol injection for the mid-term interruption of pregnancy]. / Intraamniális Rivanol feltöltés középidös terhességek megszakítására.

Authors report their experiences about the use of intraamniotic Rivanol injection in the interruption of midtrimester pregnancies. Instillation was made between 15-24 gestation weeks with the use of 0.1% Rivanol solution in 108 cases. The abortion occurred averagely 36.9 hours after induction without remarkable complications in all cases. According to their experiences the intraamniotic Rivanol injection is an effective and safe method for the interruption of second-trimester pregnancies.

Mid-trimester abortion by extraamniotic Emcredil versus normal saline.

Data is presented for 40 mid-trimester abortions, induced by 0.1% Emcredil (Group 1--20 cases) and normal saline (Group 2--20 cases) by instillation in the extraamniotic space. It was observed that the 2 groups were comparable for age, parity and period of gestation. The mean induction-abortion interval was 18 hours 9 minutes in Group 1 and 19 hours 19 minutes in Group 2. Abortion was complete in 45% and 65% in Group 1 and Group 2, respectively. With a cutoff time of 30 hours, there were 3 failures, 1 in Group 1 and 2 in Group 2. The induction-abortion interval was significantly less in the more advanced pregnancies in the saline group. There was no complication in either of the 2 groups. It is hypothesized that normal saline also acts by damage of the decidual cells with liberation of prostaglandins locally. Also since normal saline is a cheap and easily available commodity with no contraindication for its use and no side-effects, it seems to hold a lot of promise for induction of mid-trimester abortion.

New technique for managing second trimester intrauterine fetal death.

In this study, a new method for terminating second trimester pregnancies complicated by intrauterine fetal death is analysed. The technique consisted of a combination of extraamniotic ethacridine lactate with intramuscular sulprostone (16-phenoxy-omega-17,18,19,20 tetranor PGE2 methyl sulfonylamide). Objective documentation of the efficacy of this method was obtained by continuous monitoring of intrauterine pressure in two patients. The method was found to be simple, safe, cheap and effective and deserves increased acceptance.

Second trimester abortion with ethacridine lactate plus carboprost--which is the best time to administer the carboprost?

Extra-amniotic ethacridine lactate plus intramuscular prostaglandin has become a popular method for terminating second trimester pregnancies. In this study, intrauterine pressure was continuously monitored in order to objectively compare the efficacy of 3 different times of administration of Carboprost (15-methyl PGF2 alpha) - at 2 hours, 4 hours and 8 hours after the instillation of ethacridine lactate. The best results were obtained with the administration of Carboprost 8 hours after the instillation of the extra-amniotic ethacridine lactate. The synergistic effect of ethacridine lactate and Carboprost is optimal after this time. This is probably because the ethacridine lactate will have produced sufficient cervical ripening to ensure optimal efficacy of the prostaglandin-induced uterine contractions in expelling the products of conception.

International colloquy on the management of intrauterine fetal death.

Management of intrauterine fetal death is a common medial problem. The risks of time-related development of consumptive coagulopathy and intrauterine infection with speticemia force the clinician to terminate pregnancy as soon as possible while still taking into account the mental distress of the patients. Rapid surgical intervention (e.g. hysterotomy) is associated with a considerable risk of maternal morbidity and mortality. The following reports from international experts present a topical survey of current methods for the management of fetal demise. This background of clinical experience from different countries should serve to stimulate discussion on problems associated with intrauterine fetal death and ultimately lead to practical advice that will be of benefit to the patients.

Vasectomy with rivanol injection and fertility control by vital staining with eosin.

A material is presented of 66 males who were treated with Rivanol injection during vasectomy in order to obtain immediate sterility. The fertility control was established using vital eosin staining on seminal fluid at home. One case of recanalization occurred. All patients had infertile spermatozoa or aspermia 10 days after surgery. Increased frequency of complications was not observed. Vital staining with eosin is found to be practical and easily used.

PIP: A trial of injection of the vas deferent duct with ethacridine lactate (Rivanol) 1% as a perioperative procedure during vasectomy, to ensure immediate sterility was conducted on 66 Danish men between January 1983 through January 1984. 14 patients were excluded for personal or technical reasons or did not comply with follow up, leaving 52 study subjects. Vasectomy was performed under local anesthesia by resecting 0.5-1.0 cm of the vas. The central vas was flushed with 2.0 ml Rivanol 1% 4 times at 2 min intervals before ligation and embedding in membranes with Dexon 3.0. Patients were instructed in vital staining with eosin as follows: collect semen, 30 minutes later draw up in a capillary tube, apply 1 drop on a slide layered with dried eosin, mix 1 minute, cover with a clean slide, draw the cover slide off longitudinally, and air dry. All subjects had infertile (red stained) sperm or azoospermia at 10 days. Azoospermia occurred in 51 men (86.7%) within 3 months. 2 patients developed sperm granuloma, one with infection that required re-operation because of recanalization. 80% complained of pain which was associated with the wound in 73%, but 33% noted pain in the lower abdomen, often described as an oppressive feeling, probably due to Rivanol, usually disappearing within 10 days. there were no pregnancies. This were no pregnancies. This method greatly simplified post-vasectomy follow up.

Second trimester abortion by rivanol with or without cervical dilatators. A randomized comparison.

Fifty women undergoing second trimester legal abortion were randomly assigned to one of three groups: 1. given Rivanol and left with balloon catheter in the cervical canal with addition of oxytocin infusion. 2. same treatment as above but catheter removed and replaced by a Lamicel cervical dilatator, 5 mm in diameter; 3. as group 2, but with a 6 mm Laminaria tent inserted. Induction-abortion interval and need for analgesics were recorded, as well as possible side effects and complications. No statistical differences were found between the three groups for any of the parameters. We have thus not been able to show any advantages of using Laminaria or Lamicel osmotic cervix dilatators in second trimester abortions.

Comparison of the results of card, rivanol, complement-fixation, and milk ring tests with the isolation rate of Brucella abortus from cattle.

Specimens from 4,553 cows were examined by card, Rivanol, and complement-fixation (CF) tests and bacteriologic culture. A ring test was performed on milk from 1,003 of these cows. The isolation rate of Brucella abortus correlated directly with antibody titers, and the field strain predominated in adult-vaccinated cows when the Rivanol test titer was greater than + 100 and the CF test titer was greater than 4 + 40. The CF test had the best balance of sensitivity and specificity in adult-vaccinated cows. The false-negative rate for the Rivanol and CF tests was higher in nonadult-vaccinated cows.

Interruption of pregnancy by cervical rivanol predilatation.

Experience obtained in 1361 cases of first trimester pregnancy interruption with cervical Rivanol predilatation is reported. Rivanol-induced predilatation of the cervical canal prior to interruption was found to be an efficient procedure. The dilating effect of Rivanol could not be enhanced by i.m. administration of 5 IU oxytocin. After the interruption of more advanced pregnancies a higher degree of dilatation of the cervix was observed. The necessity of further dilatation prior to vacuum aspiration is, in the majority of cases, not higher than 2-2.5 H, which is insignificant on the softened cervix. The immediate complications of medical induction and interruption were infrequent and not severe. Thus, cervical predilatation with Rivanol prior to vacuum aspiration is a recommendable method of pregnancy interruption, worthy of widespread application.

Early complications of first trimester interruption of pregnancies with rivanol predilatation.

The early complications of the non-invasive interruption of 1361 first trimester pregnancies induced by Rivanol predilatation were studied. For this purpose the patients were called back for follow-up examination 6 weeks after the operation. The number of patients reporting at the control examination was 769. The number of febrile complications of genital origin was low. Slight postoperative bleeding exceeded the amount of normal menstruation only in 4.9% of the patients and, in general, it did not last longer than 7 days. The same applied to abdominal and lumbar complaints. The proportion of early complications was lower than after interruptions with the D + VA and D + C methods. The first menstruation after the operation did not differ from the earlier menstruation pattern of the particular patient in 75.9% of the cases. This also showed that the use of Rivanol did not involve lasting and severe damage to the endometrium.

Examination of gestations and deliveries subsequent to rivanol-induced interruption of first trimester pregnancies.

The pregnancies and deliveries of 550 parturient women were studied. The women previously had undergone interruption of pregnancy induced by Rivanol predilatation of the cervical canal. As controls served the data of 557 pregnancies and deliveries in which the pregnant women had formerly undergone invasive interruption of pregnancy. In addition the data of further 531 women were studied whose last delivery occurred before term or of a small for dates baby. The examinations showed that the necessitating cerclage occurrence of cervical incompetence was significantly lower in pregnancies following non-invasive interruption than after those following invasive interruption. There were no differences in the start and course of delivery and in the number of complications that could be traced back to the method of interruption. There was no difference in the intactness, site of adherence, separation and gross structure of the placenta. The condition of neonates at delivery was similar in the two groups. On the other hand, in the group of invasive interruptions the proportion of neonates that needed medical treatment was higher. An important observation was that after non-invasive interruption the proportion of preterm and small for dates births was significantly lower. These findings may be important in everyday practice.

Radiometric assay for direct quantitation of rat liver cytochrome P-450b using monoclonal antibodies.

A simple and sensitive assay has been developed that is capable of detecting as little as 0.2 ng of the major isozyme of cytochrome P-450 (P-450b) isolated from the livers of phenobarbital-induced rats. This assay employs monoclonal antibodies generated against cytochrome P-450b to directly quantify the levels of this enzyme in various tissues. Separation of bound from free labeled antibody is achieved by using 6,9-diaminoacridine lactate (Rivanol). The useful range of the assay is between 1 and 100 ng of P-450b.