ABSTRACT
AIMS: The interaction of quinolone and indoloquinazoline alkaloids concerning their antimycobacterial activity was studied. METHODS AND RESULTS: The antimycobacterial and modulating activity of evodiamine (1), rutaecarpine (2) and evocarpine (3) was tested on mycobacteria including three multidrug-resistant (MDR) clinical isolates of Mycobacterium tuberculosis. Antagonistic effects were concluded from fractional inhibitory concentration (FICI) values. Interaction energies of the compounds were calculated using GLUE docking module implemented in GRID. 1 and 2 exhibited weak inhibition of rapidly growing mycobacteria, however, 1 was active against Myco. tuberculosis H37Rv (MIC = 10 mg l(-1) ) while 2 was inactive. Both 1 and 2 showed a marked antagonistic effect on the susceptibility of different mycobacterial strains to 3 giving FICI values between 5 and 9. The interaction energies between compounds 1 and 2 with compound 3 suggested the possibility of complex formation in solution. CONCLUSIONS: Indoloquinazoline alkaloids markedly reduce the antimycobacterial effect of the quinolone alkaloid evocarpine. Complex formation may play a role in the attenuation of its antimycobacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study gives a striking example of antagonism between compounds present in the same plant extract which should be considered in natural product based screening projects.
Subject(s)
Alkaloids/antagonists & inhibitors , Anti-Bacterial Agents/pharmacology , Drug Antagonism , Mycobacterium tuberculosis/drug effects , Quinazolines/antagonists & inhibitors , Quinolones/antagonists & inhibitors , Humans , Mycobacterium tuberculosis/physiology , Plant Extracts/antagonists & inhibitors , Tuberculosis/drug therapy , Tuberculosis/microbiologyABSTRACT
A modified ultra-rapid freezing technique was introduced in January 1989 in our clinical in-vitro fertilization freezing programme. Thus, we wish to report our 1 1/2 year experience with ultra-rapid freezing as a simple and inexpensive method of routine cryopreservation. Of 181 frozen-thawed embryos, 110 (61%) survived with 50-100% blastomeres intact, and were used in 91 embryo replacements. Nine clinical pregnancies were established including two sets of twins. There was one miscarriage and one ectopic pregnancy. So far, five patients have delivered six normal, healthy infants and two other pregnancies are normally ongoing, including another twin pregnancy. These results were similar to those obtained by the conventional slow freezing method using propanediol. There is no doubt that there is a marked advantage of ultra-rapid freezing when compared to previous methods in terms of cost and time. We therefore believe that more clinical attention should be given to ultra-rapid freezing and it should become increasingly the method of choice for human embryo freezing in IVF programmes.
Subject(s)
Cryopreservation/methods , Embryo, Mammalian , Fertilization in Vitro/methods , Clinical Protocols , Cryoprotective Agents , Dimethyl Sulfoxide , Female , Humans , Phosphates , Pregnancy , Sodium ChlorideABSTRACT
A human egg and embryo freezing program for non-fertilized eggs and spare embryos has been established in our in vitro fertilization clinic. In the following we report on our first experience with different methods of human pre-embryo cryopreservation. In a simple evaluation we have compared different conventional freezing techniques using cryoprotectant substances such as glycerol, DMSO and 1.2 propanediol and an "ultrarapid" technique. So far we have achieved 6 normal ongoing and 2 biochemical pregnancies out of a total number of 61 embryo transfers. This equals 9.8% pregnancy rate per embryo transfer. Two methods seem preferable, i.e. sucrose and 1.2 propandiol which has the highest success rate and the ultrarapid method which gives a good rate of embryo survival on the one hand and a simple handling on the other.
Subject(s)
Embryo Transfer/methods , Fertilization in Vitro/methods , Tissue Preservation/methods , Female , Follow-Up Studies , Freezing , Humans , PregnancyABSTRACT
A simple and rapid assay for estimation of total urinary estrogens is presented. The test is based on a commercial latex agglutination inhibition assay designed for urinary estrogens in pregnancy. To obtain the appropriate sensitivity range for the application of the test it was necessary to concentrate the urine using self contained C 18 mini cartridges. A fairly good correlation was found between the obtained values from the urine and estradiol-17 beta estimated by radio-immunoassay in serum (correlation coefficient r = 0,77). Comparing those results and regarding the number of follicles present at ultrasonic examination, and/or laparoscopy a value of 23,79-31,29 mg/l TE in urine/follicle was calculated according to 300-400 pg/ml serum/follicle, at which ovulation should be induced. Even withstanding the inherent limitations of this semiquantitative test and some loss of precision in terms of absolute values, when combined with ultrasound, excellent guidelines were established by this rapid and simple test to determine ovulation induction by hCG.
