Commentary on Gressel's review

Transgenic Research -     

Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine.

OBJECTIVE--To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN--Double blind, double dummy, placebo controlled study with three parallel groups. SETTING--Six specialist lipid clinics in the United Kingdom. PATIENTS--128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES--Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS--Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS--Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations.     

Oestrogens and androgens in blastocoelic fluid and cultures of cells from equine conceptuses of 10-22 days gestation.

Six samples of blastocoele fluid recovered between 10 and 22 days gestation were tested in human clinical radioimmunoassay systems measuring total oestrogens and total androgens. The results were erratic but in 5 cases measurements for oestrogen equivalent to between 1000 and 70,000 pg/ml and for androgen between 1000 and 85,000 pg/ml were recorded. Cells from two blastocysts were cultured in medium 199 with and without horse serum. When the used media were assayed, values equivalent to at least 8000 pg oestrogen/ml were obtained on 7 of 11 occasions. In 9 of 11 samples the androgen concentration exceeded 700 pg/ml. In control media the oestrogen and androgen concentrations did not exceed 120 and 360 pg/ml respectively.     

The meiotic stage of preovulatory oocytes in mares

Confusion exists as to whether the oocytes of the domestic horse are ovulated at the first meiotic metaphase (MI) or the second (MII). In this study eight oocytes were collected from the preovulatory follicles of 16 mares 36 h after human chorionic gonadotropin CG treatment. Six of the eight oocytes were judged to be at MII by the presence of the first polar body and this judgement was confirmed by semithin sectioning in one. Of the two that had no polar body, one was found to be at MII after fixation for chromosomal analysis and the meiotic stage of the other remained undetermined. Since all seven oocytes yielding conclusive evidence were at MII, it was concluded that horse oocytes, like those of most mammals studied, are ovulated after completion of the first meiotic division and formation of the first polar body.     

Sexing two-week old bovine embryos by chromosomal analysis prior to surgical transfer: Preliminary methods and results

Chromosomal analyses of 30 day-14 and four day-15 bovine embryos were attempted from direct preparations of excised trophoblast cells prior to their surgical transfer singly to recipient heifers. The embryos varied in length from 0.6 mm to about 80 mm. Sex determination was successful in 20, uncertain in three and unsuccessful in 11 embryos. Failure to sex embryos was due to the poor quality or absence of metaphase spreads. Transfer of 32 biopsied embryos resulted in 12 pregnancies (37.5%) and seven delayed returns (>26 days) to estrus (21.8%): of these, 10 pregnancies were from eight sexed and two questionably sexed embryos, six of the delayed returns were also from sexed embryos. Thus it appeared that the ability to sex was related to an increased chance of embryo survival after transfer. Transfer failures were attributed to several possible factors such as embryo damage prior to biopsy, the removal of too much trophoblast at biopsy, chromosomal abnormalities and estrus asynchrony of recipient and donor. To date seven, correctly sexed, phenotypically normal fetuses have been obtained: three at term, three at slaughter between 184 and 198 days of gestation, and one spontaneously aborted at 193 days. An eighth phenotypically normal fetus, born at term from one of the questionably sexed embryos, was incorrectly sexed. The overall pregnancy rate of 37.5% in this study compared reasonably well with that of 45.8% reported for single surgical transfers of day-14 and day-15 embryos in a concurrent study.     

Anatomy of the reproductive tract of the female muskox (Ovibos moschatus)

Reproductive tracts from 23 female muskoxen were collected from the Canadian high arctic during annual native muskox hunts. Twenty tracts were collected during the late breeding season and the last third of pregnancy or anoestrus, with 3 additional specimens taken just before the breeding season in August. The non-gravid muskox uterus was very similar to that of sheep and goats except for two features found in parous muskoxen. The first was endometrial pigmentation found only in the caruncles and associated with a dense collection of lipofuscin granules in the endometrial stroma. The second was a prominent 5 mm deep band of muscular tissue protruding from the antimesometrial border of the uterine horns throughout most of their length. The pregnant uterus and the fetal membranes of the muskox resembled homologous structures in domestic ruminants. However, there was no morphological evidence of a corpus luteum during late pregnancy, apart from a luteal scar in the ovary ipsilateral to the pregnant horn. Of the 4 females collected at the end of the breeding season, 2 lactating females were apparently not cyclic while 2 others had more than one CL, suggesting that they had undergone at least 2 cycles without conceiving or remaining pregnant.     

Equine zona pellucida and capsule: Some physicochemical and antigenic properties

The capsule which surrounds the pre-attachment equine embryo has been compared with the zona pellucida (zp) that it replaces, as well as with the rabbit blastocyst coverings, by means of physicochemical and immunological methods. Trypsin solution at pH varying between 7.5 and 9.0 completely solubilized the capsule, as did Na borohydride. However, solutions of pH 2.0 or 12.0, urea, high temperature (65°C, 60 min or 80°C, 30 min), mercaptoethanol and dithiothreitol were able to solubilize the zp but not the capsule at the concentrations used. Indirect immunofluorescence on cryostat sections and whole mounts of fresh or frozen-thawed material showed that 1) common antigens are shared by equine, porcine and bovine zp; 2) day 7 to day 15.5 capsule reacted with anti-capsule-serum but not with anti-zp-serum except for a few patches on the surface of the capsule; 3) anti-capsule-serum, but not anti-zp-serum, reacted with the capsular material recovered along with a broken day 27.5 conceptus; 4) anti-capsule-serum does not react with rabbit blastocyst coverings; 5) anti-capsule antibodies can be absorbed from the anti-capsule-serum by uterine proteins from either pregnant or non-pregnant mares; and 6) the capsule does not contain mouse laminin-like material.