NIM-76, the odorous and volatile fraction of neem oil, was investigated for its antifertility activity in vivo in rats, rabbits and rhesus monkeys. The drug is effective when applied before coitus but not so when applied during post-coital stages. It, therefore, appears to act mainly by its spermicidal effect. No alteration in the estradiol (E2) and progesterone (P) values was observed after the application of the drug in monkeys.

Neem oil, an oil extracted from the seeds of Azadirachta indica has been found to act as a good spermicidal agent. Pre and post coital application of the oil intravaginally prevented pregnancy in rhesus monkey.

Depot-medroxy progesterone acetate (DMPA) was jet deposited into the uterus/cervix of rats, rabbits and rhesus monkeys with the help of a modified jet injection apparatus. Since the drug was delivered under pressure, it was distributed deep into the muscular layers around the place of deposition. After one deposition the drug acted as an effective contraceptive for a period of three months. The merits of this delivery technique are discussed.

The volatile, odorous fraction of neem oil coded as NIM-76 obtained by steam distillation was investigated for in vitro spermicidal activity. The data showed that the minimum concentration which inhibited spermatozoal motility was 0.25 mg/ml for rat and 25 mg/ml for human spermatozoa. The effect of the drug on spermatozoal motility was found to be dose-dependent. The activity of this drug was not altered in the presence of vaginal or cervical mucus. Intra-vaginal application of NIM-76 in rabbits showed no irritation to the vaginal mucosa.

The purpose of this study was to determine whether the antifertility effect of the antiestrogenic substance neem oil, extracted from the seeds of Azadirachta indica, acts directly on the uterus or through absorption from the vaginal epithelium into the general circulation. In 4 groups of rats the left uterine horn was ligated 2 days after coitus. Rats in group A were used as controls. In group B 25 mcl neem oil was administered intravaginally on days 2-4 with the animals in head down position for 3 minutes to ensure that the neem oil was uniformly distributed in the vagina. In group C the neem oil was administered on days 4-6, and in group D on days 7-9, i.e., after implantation. The ligatures were removed on day 12, and no viable implantation sites were found in either horn. The study showed that the neem oil exerts its effect on the endometrium through absorption into the general circulation from the vaginal epithelium. The antiestrogenic quality of neem oil explains its anti-implantation effect. But the postimplantation effect, which caused implanted fetuses to be either resorbed or expelled, may be due to direct toxicity, to a fall in progesterone level, or to interference with the uterine utilization of progesterone.

Haematologic studies were carried out in 20 high altitude natives during two months stay at plains (200 m) and on their return to an altitude of 3,500 m. Haemoglobin, erythrocyte count, haematocrit and reticulocyte count decreased rapidly on arrival to plains and attained minimum level by the end of fourth week. All these parameters increased rapidly on return to high altitude and were found to attain maximum values by 23rd day on return to high altitude. Mean cell volume and mean cell haemoglobin showed significant increase at altitude. Blood volume and red cell mass increased significantly at altitude. It is concluded that the high altitude natives of Ladakh were well adapted to hypoxic environment due to normocythaemic hypervolemia.

Indigenously available neem oil in its natural form was tested for its spermicidal activity (in vitro and in vivo). Undiluted neem oil was found to possess strong spermicidal action (within 30 seconds) against rhesus monkey and human spermatozoa in vitro. When used intravaginally in a dose of 20 mcl in rats and 1.0 ml in rhesus monkeys and human subjects before sexual intercourse the oil was found to be 100% effective in preventing pregnancy in the test subjects. The oil did not reveal any side effects as confirmed by histopathological studies. (authors)

Zusammenfassung: Ionisiertes Kupfer als empfängnisverhütendes Mittel beim männlichen Rhesusaffen Kupfer wurde mittels Iontophorese bei einer Stromstärke von 7 mAmp. über fünf Minuten im Vas deferens des Rhesusaffen eingelagert. Nach der Ioniesierung wurde ein Verlust der Motilität der Spermatozoen bei Zunahme der toten und abnormalen Formen gefunden. Auf der Seite der Kupfer-Deponierung ließen sich atrophische Veränderungen im Vas deferens (Erosionen, Schichtung des hochcylindrischen Epithels in diesen Bezirken, engeres Lumen, keine Spermatozoen) nachweisen. Am epididymalen Ende zeigte das Vas deferens normale histologische Struktur mit beweglichen Spermatozoen (kein Lumenverlust). Der Hormonstatus blieb unverändert. Dieses Verfahren war über einen Zeitraum von 7 Monaten wirkungsvoll.

Copper was deposited by iontophoresis into vasa deferentia of animals, using 1 m. amp. current for 30-90 sec. in rat and 3 m. amp. current for 60 sec. in rabbits. The method was effective for a period of 9 months as a contraceptive. The effect of the metal was localised at the site of deposition and there was no effect on other reproductive organs. The mating behaviour and testosterone levels did not change. The utility of the technique in male contraception is discussed.

Body fluid compartments were studied in a group of high altitude natives after a stay of two months at sea level and during 12 days at an altitude of 3,500 m. Measurements of total body water and extracellular water were made on day 3 and 12 of reinduction to altitude, while plasma volume was measured on day 12 only. The intracellular water, blood volume and red cell mass were computed from the above parameters. Total body water and intracellular water decreased by 3.3% (P<0.001) and 5.0% (P<0.001) respectively by the 3rd day at altitude and did not change thereafter. Extracellular water increased progressively at altitude, but the increase was not significant. Blood volume and red cell mass increased significantly while plasma volume decreased at altitude. These data were compared with that of low landers. This study suggested body hypohydration on high altitude induction in low landers as well as in high altitude natives on reinduction.

Body fluid compartments were studied in a group of sea level residents at sea level and during 12 d of acute exposure to an altitude to 3,500 m. Measurements of total body water and extracellular water were done on the third and 12th days of exposure, while plasma volume was measured on 12th day only. The intracellular water, blood volume, and red cell mass were computed from the above parameters. Total body water and extracellular water decreased progressively, the decrease being 4.7% (p less than 0.001) and 6.0% (p less than 0.05) respectively on the 12th day. Plasma volume and blood volume decreased significantly with a slight increase in red cell mass. Intracellular water, computed from total body water and extracellular water, decreased by 4.3% on 12th day. This study suggested hypohydration on acute altitude exposures.

Haematologic changes were studied in 16 albino rabbits during acclimatisation, deacclimatisation, and reinduction to hypobaric hypoxia. Of these, four animals died during reinduction. Haemoglobin, haematocrit, and red blood cell count attained maximum values by the 15th day during acclimatisation and by the 10th day during reinduction. Reticulocyte count reached maximum level by the fifth day, both during acclimatisation and reinduction. All these parameters returned to initial control levels by the 10th day of deacclimatisation. The erythrocytes became macrocytic during acclimatisation and remained so during deacclimatisation and reinduction. Blood volume increased on acclimatisation, returned to control values during deacclimatisation, and remained low at this level on reinduction. Red cell mass increased both during acclimatisation and reinduction and returned to control levels on deacclimatisation. Plasma volume did not change on acclimatisation and deacclimatisation, but was reduced on reinduction. The erythrocyte life span and erythrocyte glutamic oxaloacetic transaminase (EGOT) decreased during acclimatisation and reinduction. There was no change in RBC osmotic fragility, indicating no change in the integrity of the red cell wall. The deaths during reinduction were possibly due to haemoconcentration and increased blood viscosity as a result of reduction in plasma volume. It has been concluded that reinduction to hypoxia after a phase of deacclimatisation imposes a more severe stress than experienced during acclimatisation.

Body fluid compartments were studied in rabbits divided into three groups--control, exposed to acute hypoxia, and exposed to hypoxia after treatment with 2 mg frusemide intramuscularly. Total body water, extracellular body water, and plasma space were determined using the triple radiotracer technique. Total body water decreased insignificantly with no change in extracellular body space on exposure to hypoxia. Plasma volume and blood volume showed a significant decrease with a significant increase in haematocrit. In rabbits pretreated with frusemide, total body water, extracellular body water, plasma volume, blood volume, and interstitial fluid space decreased significantly on hypoxic exposure. This study suggested hypohydration on acute hypoxic exposure with a loss of intracellular water, while pretreatment with frusemide resulted in further hypohydration with a loss from both intracellular and extracellular compartments. The results have been discussed in relation to suggested use of diuretics on induction to high altitude.