A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Bioactivity of marine organisms: Part VIII--Screening of some marine flora of western coast of India.

Methanolic extracts of 31 botanically identified species of marine flora, collected from Gujarat Coast, have been screened for a wide range of biological activities. Of these, 3 extracts showed anti-implantation, 2 had antiviral, 2 showed hypotensive, 1 had anti-inflammatory while 12 extracts showed diuretic activities. The antiviral activity; against EMCV, was confirmed in one alga. The active principles and results of these studies are reported.

Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats.

Hexane extract of the seeds of Nigella sativa L. prevented pregnancy in Sprague-Dawley rats treated orally at 2 g/kg daily dose on days 1-10 post-coitum. Significant antifertility activity was also observed in its column fractions and subfractions. At contraceptive dose, the active hexane extract exhibited only mild uterotrophic activity comparable almost to 0.002 mg/kg dose of 17 varies; is directly proportional to-Ethinylestradiol, but was devoid of any estrogenicity in the immature rat bioassay.

Diagnostic and prognostic significance of serum and tissue trace elements in breast malignancy.

50 cases of breast malignancy constituted the study group. 26 age and sex matched formed the control group. Serum and tissue trace element viz copper, zinc, selenium and molybdenum levels were estimated by atomic absorption photometry. The study group showed significant hypercupremia and molybdenemia, hypozincaemia and hyposeleniamia. The reversal of trend was documented after therapy. The tissue level of copper and molybdenum was high and zinc and selenium was low. An association between serum and tissue level of trace element, stage, histological differentiation was observed. It was postulated that levels of trace elements may help in diagnosis and prognosis of disease.

Antigestagenic activity of Ixora finlaysoniana in rat.

Oral administration of crude ethanolic extract of the serial parts of Ixora finlaysoniana Wall. ex G. Don to adult female rats at 250 mg/kg dose on days 1-5 or 1-7 post-coitum prevented pregnancy in 100% rats. The extract was also effective when administered on days 1 or 1-3 post-coitum, but the minimum effective dose increased with decreased duration of administration and was 1000 mg/kg and 500 mg/kg, respectively, in the two schedules. At lower doses, a significant reduction in implantation number and increased post-implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed after administration of 1000 mg/kg dose of the extract during the peri-implantation period. A slight acceleration in tubal transport rate of embryos and delay in blastocyst formation were observed in rats treated postcoitally with the single anti-implantation dose of the extract. Significantly fewer embryos were recovered after their entry into the uterus. Except in one rat receiving 250 mg/kg dose of the extract on days 1-5, in which one apparently normal zona-free blastocyst was recovered from the uterus, uterine flushings of none of the nonpregnant animals contained any unimplanted embryos by day 10 post-coitum. In immature rat bioassay, the extract was found to possess estrogenic activity as evidenced by dose-dependent increase in uterine weight and cornification of the vaginal epithelium at doses ranging from 50-1000 mg/kg. At the 500 and 1000 mg/kg doses, it also induced premature opening of the vagina. Taking 100% increase in uterine weight as the parameter, the extract was found to be about 1.6X10(5) times less estrogenic than ethinylestradiol. The extent and duration of estrogenic responses exerted by single contraceptive dose of the extract were also markedly lower than that induced by ethinylestradiol. The extract was devoid of any estrogen antagonistic or synergistic activity and did not affect ovarian prenidatory estrogen or progesterone synthesis. The findings indicate that the extract at its contraceptive dose a) exerts a differential estrogenic response at the fallopian tube and the uterine levels, b) does not appear embryocidal, but causes slight asynchrony in development and tubal transport rate of pre-implantation embryos, which together with their loss through vagina after entry into the uterus, due to estrogenic action of the extract, might contribute to its anti-implantation action, and c) its anti-implantation and post-implantation resorptive actions are not mediated via altered ovarian function.

PIP: Colony-bred immature (25-35 gm) and adult (180-220 gm) Sprague-Dawley rats were administered orally an 85% ethanolic extract of powdered aerial parts of Ixora finlaysoniana suspended in distilled water. The extract prevented pregnancy in 100% of rats at a dose of 250 mg/kg on days 1-5 or 1-7 post coitus. However, 1000 mg/kg and 500 mg/kg doses were required to achieve complete contraception increasing with decreased duration of administration of the extract. At sub contraceptive doses, a significant reduction in implantation and a marked increase in post implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed at 1000 mg/kg dose of the extract administered on days 5-7 post coitus. Single oral anti implantation dose (1000 mg/kg) of the extract administered within 24 hours of coitus induced slight acceleration of tubal transport of embryos. Fewer extract-treated rat embryos were recovered from the Fallopian tubes compared with controls on days 4 and 5 to (p 0.01). 1 normal zona free blastocyst was also recovered from the uterine flushings of a rat treated with a 250 mg/kg dose on days 1-5 post coitus, but uterine flushings of none of the 43 remaining nonpregnant rats treated with the various doses on days 1, 1-3, 1-5, or 1-7 yielded any unimplanted embryos by day 10 post coitus. Doses ranging from 50 to 1000 mg/kg once daily for 3 consecutive days induced a dose-independent increase in uterine weight (p 0.001) vs. controls and cornification of the vaginal epithelium in bilaterally ovariectomized rats. Premature opening of the vagina was observed only at 500 and 1000 mg/kg doses. A single oral contraceptive dose of 1000 mg/kg induced a significant increase (p 0.05) vs. the control group in uterine weight and premature opening of the vagina and 40-60% vaginal cornification in all treated rats. In comparison, a single oral contraceptive dose (1.5 mg/kg) of ethinyl estradiol induced stronger and longer estrogenic responses; uterine weight gain at all time intervals was significantly more than with the extract.

A review of Indian medicinal plants with interceptive activity.

PIP: 48 Indian plant species mentioned in ancient literature as inducers of menstruation or abortion have been tested in rats or mice for anti-implantation activity. An additional 65 plants not cited in old sources have been tested for anti-implantation activity. All are tabulated by systematic and local name, plant part used, activity reported in recent literature, estrogenic or anti-estrogenic activity, and literature reference. 40 plants were found to have anti-implantation activity. 23 plants were tested in rodents for abortifacient activity, and all but 2 were active in 50% or more. Some of these have been extracted for the active alkaloid, and one extract, from Pueraria tuberosa, is being tested clinically. Many of the abortifacients were traditionally used either as coating of abortion sticks to be inserted in the cervix, or as gastrointestinal irritants. Those with toxic, neurotoxic, or estrogenic effects were eliminated for further tests. The fact that many plants were found to be active even though they were not mentioned in classic literature, suggests that all Indian plants should be tested at random for anti-implantation effects, under strict WHO guidelines.^ieng

Postcoital contraceptive efficacy and hormonal profile of Lepidium capitatum.

PIP: Hexane soluble fraction of the Lepidium captiatum plant collected in Himachal Pradesh, India, was administered orally to colony bred albino mice, rats, and golden hamsters to test the plant's postcoital antifertility efficacy and estrogenic and antiestrogenic activities. 2.5 kg of the whole air-dried and powdered plant was extracted 4 times with 90% ethanol, which was evaporated under reduced pressure. The resultant aqueous suspension was partitioned 3 times with hexane and concentrated under vacuum to achieve the hexane soluble and hexane insoluble fractions. Oral administration of 250 mg/kg of crude ethanolic extract of the whole plant on postcoital days 1-5 prevented pregnancy in about 77% of mated female rats. The hexane soluble fraction inhibited pregnancy in 100% of the rats at a dose of 250 mg/kg and in 50% at 125 mg/kg. In comparison to controls, there was a significant reduction in implantation number at both 125 mg/kg and 625 mg/kg doses. The extract failed to prevent pregnancy in hamsters even at a daily dose of 500 mg/kg on postcoital days 1-5. No contraceptive efficacy of the hexane insoluble extract was observed in rats or hamsters. The extract exhibited potent estrogenic activity at the contraceptive dose, without antiestrogenic activity. A significant uterotrophic effect was seen even at 1/40 of the contraceptive dose. When administered orally for 3 consecutive days, the hexane soluble fraction induced normal implantations at 250 mg/kg and lower doses in adult female mice undergoing experimentally induced delayed implantation. The maximum response in terms of the percentage of pregnant animals and the average number of implantations was observed at 125 mg/kg dose. The experimental results confirm the frank estrogenicity of the extract.^ieng

Research on plants for fertility regulation in India.

PIP: This present review of Indian plants investigated for fertility regulation includes published literature of the country and unpublished data of the Central Drug Research Institute (CDRI), located in Lucknow, India. Publications without supportive experimental data have not been included. It is evident from the data presented in the tables that most of the investigators have failed to include the valuable information on the time and place of collection and proper botanical authentication, if conducted, in their publications. The plants evaluated at the Institute do contain this information and their herbaria sheets are available at CDRI. The plants, with part used, type of extract, isolated compound/chromatographic fraction, dose, route and schedule of administration with animal used, and percentage activity are given in tables. The plants are classified according to their activity profile and presented accordingly. Plants for which the hormonal profile or toxicity data have been reported are dealt with under each type of activity. Most of the investigators did not develop the active plants, probably because of inconsistent results in repeat tests or lack of facilities. Major attention has been devoted to identifying plants with interceptive properties. The schedules used are more or less uniform and acceptable. On the basis of preliminary toxicity data, extracts/compounds from "Aristolochia indica," "Artemisia scoparia," "Hibiscus rosa sinensis," "Laccardia lacca," and "Plumbago zeylanica" exclude themselves from consideration for follow-up. Wherever done, the hormonal profiles revealed estrogenic activity in active extracts/fractions/compounds from "Artabotrys odoratissimus," "Datura quercifolia," "Daucus carota," "Embelia ribes," "Hibiscus rosa sinensis," "Pueraria tuberosa" and "Tabernaemontana heyneana." Thus they are not ideal for follow-up. Some more plants can be excluded initially because of low activity or equivocal reports on activity. The remaining plants, in order of priority, for follow-up should be "Ensete superbum," "Achyranthes aspera," "Lygodium flexosum," "Sapindus trifoliatus," "Polygonum hydropiper," and "Abrus precatorius." The next priority could be given to plants with weak estrogenicity. The CDRI has observed 100% anti-implantation activity by 4 plants in hamsters. These should be the potential plants for development since they appear to interfere with progesterone synthesis or utilization.^ieng

Screening of Indian plants for biological activity: Part VII--Spermicidal activity of Indian plants.

PIP: Extracts of about 1600 Indian plants were tested for spermicidal activity. A small quantity of rat vasal or epididymal contents was placed on 2 drops of plant solution, mixed, and examined under a phase contrast microscope. Results were scored positive if 100% of spermatozoa became immotile. Tests were repeated 3 times. and sperm revival tested by addition of buffer to the immobilized sperm sample. Plant extracts showing positive activity were tested on liquified human semen. 30 plants showed spermicidal activity in rats, of which 16 caused instantaneous immobilization of human spermatozoa. Studies are underway on the isolation of active constituents and subsequent structural relationships.^ieng