Vaginally administered 16, 16-dimethyl-prostaglandin E2 as an agent for pre-operative cervical dilatation

Twenty-one women in the 10th–12th week of pregnancy were treated prior to vacuum aspiration with vaginal suppositories containing 16, 16-dimethyl-PGE₂ (free acid). An average total dose of 3.4 mg led to abortion or adequate cervical dilatation in all patients. Based upon previous experience with the compound, no prophylactic anti-emetic or anti-diarrhetic medication was given. Gastrointestinal side effects were minimal. Excessive bleeding was not observed. In two cases, slight temperature elevation was noted prior to abortion. The low incidence of side effects in combination with the effectiveness of the compound help to make this method an attractive therapeutic adjunct to vacuum aspiration beyond the 10th week of gestation. Under the experimental conditions of this study, the results suggest that vaginally administered 16, 16-dimethyl-PGE₂ can be a safe and effective method for cervical dilatation before vacuum aspiration.     

Vaginally administered 16, 16-dimethyl-prostaglandin E2 as an agent for pre-operative cervical dilatation

Twenty-one women in the 10th–12th week of pregnancy were treated prior to vacuum aspiration with vaginal suppositories containing 16, 16-dimethyl-PGE₂ (free acid). An average total dose of 3.4 mg led to abortion or adequate cervical dilatation in all patients. Based upon previous experience with the compound, no prophylactic anti-emetic or anti-diarrhetic medication was given. Gastrointestinal side effects were minimal. Excessive bleeding was not observed. In two cases, slight temperature elevation was noted prior to abortion. The low incidence of side effects in combination with the effectiveness of the compound help to make this method an attractive therapeutic adjunct to vacuum aspiration beyond the 10th week of gestation. Under the experimental conditions of this study, the results suggest that vaginally administered 16, 16-dimethyl-PGE₂ can be a safe and effective method for cervical dilatation before vacuum aspiration.     

Vaginally administered PGF2alpha for cervical dilatation in nulliparas prior to suction curettage

Because of the need for an atraumatic method to dilate the cervix when performing artificial abortion by suction curettage, cervical dilatation following vaginally administered PGF2alpha was studied. A 50 mg PGF2alpha vaginal suppository was administered to 40 (treated group) first trimester nulliparas 3 hours prior to progressive cervical dilatation from a 19 (circumference in mm) Pratt dilator to a 35 Pratt dialator. The smallest-sized dilator that met resistance was interpreted as being the amount of clinically significant cervical dilatation. The results were compared to 20 (control group) first trimester nulliparas who received no PGF2alpha studied in an identical manner. Independent of gestational age, treated patients were dilated significantly more than the control patients. When subjects of similar gestational age were compared, PGF2alpha treated subjects were more often dilated sufficiently to perform abortion (55%) by suction curettage than control group subjects (5%). Those PGF2alpha subjects needing further dilatation to accept an appropriate sized cannula for their gestational age needed less dilatation than did those subjects of similar gestational age in the control group. No serious complications of PGF2alpha per se were observed and the most frequent side effects, vomiting and diarrhea, did not appear severe enough to limit the clinical practicability of the method.     

Method for quantitative analysis of 16, 16-dimethyl-prostaglandin E2 from plasma using deuterated carrier and gas chromatography-mass spectrometry.

The preparation of 3,3,4,4-²H₄16,16-dimethyl-prostaglandin E₂ (PGE₂), 16,16-dimethyl-5,6-didehydro-PGE₂, and 5,6-³H₂16,16-dimethyl-PGE₂ is described. These compounds have been used for development of a gas-liquid chromatography-mass spectrometry method for quantitative determination of corresponding nondeuterated prostaglandin. The method is based on addition of a known amount of carrier to the sample and after purification and derivation the ratio between the protium and deuterium form is measured in the mass spectrometer. With this technique 40 pg of 16,16-dimethyl-PGE₂ can be determined with a precision of ±2.6%.     

Letter: On the administration of prostaglandins as a pre-operative means of cervical dilatation

Prostaglandin (PG) administration by the intramuscular or extraamniotic route has been reported to be a safe and reliable means of effecting cervical dilatation prior to 1st trimester abortion by suction curettage. At the Mulago Hospital, Kampala, a minimum of 5 cases of 1st trimester abortions were performed weekly using the Karman cannula (KC), a flexible polyethylene catheter which lessens the risk of cervical dilatation. In none of the cases was cervical dilatation required for insertion of a KC of sufficient diameter. Paracervical block with procaine 2% (10 ml) was used for analgesia; in rare cases, 10 mg of diazepan was administered orally or intravenously as a preoperative medication. Complications encountered included: 1) perforation of the uterine fundus; 2) metritis; and 3) retained products of conception. With proper instrumentation, cervical dilatation is no longer required for 1st trimester abortions. PG administered for cervical dilatation is no longer justified because it is time consuming, a source of additional expense, inconvenient, and is associated with uterine cramps and gastrointestinal side effects. In occasional cases, as in undue cervical resistance, the use of PGs may be justified.     

Vaginally administered 16,16-dimethyl-PGE2 for the induction of midtrimester abortion

Thirty patients in the 13th–20th week of gestation underwent therapeutic abortion utilizing vaginally administered 16,16-dimethyl-PGE₂ (free acid) suppositories. The first 15 patients obtained individual doses in the range of 400–1200 μg given every three hours (mean total dose 4.2 mg). In the following 15 patients a fixed dose schedule was used (800 μg followed by 1000 μg every three hours; mean total dose 5.3 mg). All but one of the 30 patients aborted. The mean induction-abortion interval for all patients was 16.8±6.9 hours (mean ± S.D.) With the fixed dose regime the success rate was 100% and the induction-abortion interval 16.0±5.9 hours. Because gastro-intestinal side effects were minimal, neither anti-emetic nor anti-diarrheic medication was required. A slight elevation of temperature was noted in five patients. The uterine response to the vaginal administration of this compound was characterized by a gradual increase in uterine tonus followed by sustained stimulation. The results are interpreted to suggest that the vaginal administration of 16,16-dimethyl-PGE₂ is a useful alternate method for the induction of second trimester abortion. Moreover, this compound seems to cause fewer gastro-intestinal side effects than other prostaglandins administered by the vaginal route at our department.     

Inducing labour with vaginally administered prostaglandin E2.

In 50 consecutive pregnant women at a 125-bed community hospital with 1000 deliveries annually, labour was induced with prostaglandin E2 administered intravaginally. There were no stillbirths or neonatal deaths, and complications in the mothers were few. In nine women (18%) oxytocin was subsequently administered because of a failure of labour to progress; in spite of this, cesarean section was required in two (4%) of the patients. The overall cesarean section rate was 6%. Prostaglandins have been used routinely to induce labour in the United Kingdom for several years. This noninvasive method is safe, effective and well received by women in a community hospital setting, including those wanting "natural childbirth".     

6-keto-prostaglandin E1 is not equipotent to prostacyclin (PGI2) as an antiaggregatory agent

A direct comparison of the relative potencies of the two antiaggregatory prostaglandins PGI2 and 6-keto-PGE1 showed PGI2 was at least 20 times more potent than 6-keto-PGE1 when tested against ADP-induced human platelet aggregation. This marked difference in potency was even more evident when the ability of PGI2 and 6-keto-PGI2 to stimulate platelet cyclic AMP levels was determined. When cyclic AMP levels were measured direct comparisons were difficult because the respective dose response curves were not parallel, but 10 ng of PGI2 was equivalent to 300 ng of 6-keto-PGE1. PGI2 was also more potent (10-20 times) than 6-keto-PGE1 as a disaggregatory agent, and the disaggregatory activity of both prostaglandins was enhanced by the phosphodiesterase inhibitor 1-methyl-3-isobutylmethylxanthine. PGI2 was also more active than 6-keto-PGE1 as an inhibitor of thrombus formation in dog coronary arteries in vivo. In vivo, 6-keto-PGE1 was at least 10 times less potent thatn PGI2, the exact difference could not be determined because 6-keto-PGE1 caused significant falls in blood pressure before anti-platelet activity could be detected. PGI2 is an intrinsically more potent anti-aggregatory molecule than 6-keto-PGE1, but these data do not rule out the possibility that some of the activities attributed to PGI2 could be the result of the conversin of PGI2 and/or 6-keto-PGF1 alpha to 6-keto-PGE1.     

Potential of doxorubicin as an antileishmanial agent.

Doxorubicin, a well characterized anticancer drug, was tested in vitro and in vivo for activity against Leishmania donovani. Activity in vitro was very high against both the promastigote and amastigote forms of this parasite with 50% effective dose (ED50) values on the order of 0.43 microM and 0.86 microM, respectively. An in vivo inhibition of spleen parasite burden up to 95% in an infected mouse model was achieved when a dosage of 625 micrograms doxorubicin/kg body weight/day was given in 4 consecutive doses, which is far less than the toxic dose. These results suggest that doxorubicin is highly active against visceral leishmaniasis and may be considered with second-line therapeutic agents such as amphotericin B and pentamidine.     

人乳头瘤病毒16型早期基因E6、E7的克隆及表达

高危人乳头瘤病毒16型的感染与宫颈癌的发病密切相关。HPV16E6和E7蛋白在大多数HPV16相关宫颈癌及其癌前病变中持续表达,因此E6和E7蛋白可作为制备HPV16相关肿瘤及其癌前病变治疗性疫苗的靶抗原〔2〕。采用套式PCR方法,从宫颈癌患者组织中扩增出E6、E7基因并成功构建了包含E6、E7的表达质粒PET-E6、PET-E7。SDS聚丙烯酰胺凝胶电泳和Western-blotting分析结果表明,外源基因E6,E7在T7启动子控制下可获得稳定表达。     

Radioprotection in E. coli by an agent from M. radiodurans.

An agent extracted from the radioresistant bacterium M. radiodurans was found to protect several strains of E. coli from X-radiation. Optimal radioprotection was observed when the repair-proficient B/r strain was irradiated in the presence of the agent under hypoxic conditions. It is proposed that this agent acts to modify damage incurred in the presence of reduced oxygen concentrations so that this damage might be subsequently repaired.     

Fate of mimosine administered orally to sheep and its effectiveness as a defleecing agent.

Mimosine was administered orally to Merino sheep once daily for periods of 1-3 days, either as the isolated compound or in the foliage of Leucaena leucocephala. A single daily dose of mimosine of 450 or 600 mg/kg body weight was effective for defleecing sheep. A daily dose rate of 300 mg/kg was effective for defleecing sheep if given on two successive days. The effectiveness of a treatment for defleecing sheep was related to the concentration of mimosine in plasma following dosing; defleecing ensued when the concentration of mimosine in plasma was maintained above 0-1 mmol/l for at least 30 h. The main products excreted in urine were mimosine and 3,4-dihydroxypyridine (DHP); small amounts of mimosinamine were also excreted. During the first day following dosing, the major excretory product was mimosine; DHP was an important component during the second and third days. In the three days following the start of dosing, between 32 and 53% of the mimosine given was accounted for as mimosine in the urine. Following an intravenous infusion of mimosine, no DHP was detected in urine; most of the mimosine was excreted intact but a small amount (c. 9%) was excreted as mimosinamine.     

Endocervical prostaglandin E2 gel for preinduction cervical softening

A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.