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Biomedical subjects

R J Fitzpatrick

Publications and source records attributed to R J Fitzpatrick.

14 recordsLinked to original sources

Antibacterial activity and mutagenicity studies of water-soluble phosphazene high polymers.

Eight water-soluble phosphazene high polymers, [NPR2]n (R, organic, water-solubilizing side-group; n, approx: 15,000) and the small-molecule counterparts of the polymers were examined for antibacterial activity against six different strains of bacteria (Escherichia coli, Salmonella typhimurium (TA 100), Salmonella pullorum, Streptococcus faecalis, Bacillus subtilis and Pseudomonas aeruginosa). Antibacterial testing was carried out by measuring zones of inhibition and changes in solution turbidity over time. In addition, the antibacterial activity of the surfaces of cross-linked poly[di(methoxyethoxyethoxy)phosphazene] (MEEP) hydrogels were investigated. A number of the high polymers, as well as the MEEP hydrogels, impeded bacterial growth. Only E. coli was unaffected by the phosphazenes. A possible explanation for the antibacterial character of the polymers is presented. The same compounds were monitored for potential mutagenic activity using the Salmonella typhimurium tester strains TA 100 and TA 98. None of the high polymers or their small-molecule analogues showed mutagenic activity in either strain of Salmonella at the concentrations tested. The use of these materials as coatings for artificial implants is discussed.

Anti-Bacterial Agents

Increased hyaluronate synthesis and changes in glycosaminoglycan ratios and molecular weight of proteoglycans synthesised by cultured cervical tissue from ewes at various stages of pregnancy.

Culture of cervical tissue with radiolabelled precursors showed that, in pregnant ewes, net hyaluronate synthesis increased between days 120-140 but that the marked polydispersity of hyaluronate remained unchanged. In the less sulphated of two proteoglycan populations, the proportion of heparan sulphate increased and that of dermatan sulphate decreased, while the less polydisperse more highly sulphated species showed a significant increase in molecular weight with pregnancy.

Animals

Dilatation of the uterine cervix.

Dilatation of the cervix at parturition necessitates changes in the physical characteristics of cervical collagen and glycosaminoglycans which are probably hormone-dependent. The infusion of prostaglandin F2alpha (PGF2alpha) into the arterial blood supply to uterus and cervix of sheep pregnant for about 125 days resulted in cervical dilatation after 24 hours but this response was inconsistent; one factor affecting the response appeared to be the progesterone status, low circulating progesterone being associated with dilatation. Preliminary experiments in goats in which pregnancy is terminated by removal of the corpora lutea at day 125, subject to modification by the administration of progesterone, indomethacin or PGF2alpha, support the view that PGF2alpha evokes softening and dilatation of the cervix but that this is blocked by progesterone.

Animals

Concentration of oestradiol, progesterone, luteinizing hormone and follicle-stimulating hormone in the jugular venous plasma of ewes during the oestrous cycle.

Changes in the concentrations of ovarian steroids and pituitary gonadotrophins were measured by radioimmunoassay in the jugular plasma of six Clun Forest ewes throughout the oestrous cycle. The concentration of oestradiol began to rise 12-14 h before the onset of oestrus from values of 11-2 +/- 0-36 (S.E.M.) pg/ml during the luteal phase to 21-1 +/- 2-01 pg/ml at -8 to 0 h (oestrus). There was no distinct increase during the luteal phase. Circulating progesterone varied in a cyclic manner with the highest values at the mid-luteal phase (3-70 +/- 0-28 ng/ml; n = 28). In five out of six ewes the concentration was still quite high (1-86 +/- 0-43 ng/ml) at 35 h before the onset of oestrus. The concentration declined rapidly thereafter, reaching minimum values about 12 h before oestrus coincident with the increase in oestradiol concentration. Plasma LH increased from very low values of 2-59 +/- 0-09 ng/ml during the luteal phase to 75-3 +/- 7-4 ng/ml about 9 h after the onset of oestrus. Two peaks of plasma FSH concentration were detected after the onset of oestrus. The first peak (171-0 +/- 35-5 ng/ml) coincided with the LH peak and the second (133-0 +/- 10-7 ng/ml) occurred about 24 h later at a time when LH values were low. The mean FSH concentration at other times during the cycle was 61-9 +/- 2-8 ng/ml.

Animals

Changes in cervical function at parturition.

In sheep and goats changes in the wall of the uterine cervix associated with parturition were studied in relation to the preparturient sequence of endocrine events. Evidence was obtained of separation of collagen fibrils, possibly due to changes in the electrostatic binding of the fibrils by glycosaminoglycans. The mechanical properties of the cervix were investigated quantitatively on isolated tissues by radial loading to destruction, and by progressive extension on a tensometer; the extension experiments revealed that at parturition (but not before) the cervical wall acts mechanically as if composed of two different tissues, one of which, the collagen layer, changes profoundly at parturition to facilitate dilatation. Resistance to dilatation (compliance) was investigated in vivo using indwelling intracervical balloons which could be inflated with water at standard speed. This permitted serial observations in the same animal during the progress of parturition induced with foetal dexamethasone (sheep) or maternal cloprostenol (goats). Compliance increased progressively in all 13 parturient animals, but not in untreated controls, and this increase occurred coincidentally with the expected fall in progesterone and rise in oestrogen concentrations: it occurred before the preparturient rise in PGF. Meclofenamic acid administration to cloprostenol treated goats successfully delayed the PGF surge and delayed parturition but did not delay the increase in compliance which reached maximum within the 36 hours of treatment with the PG synthetase inhibitor.

Animals

Concentration of steroids in bovine peripheral plasma during the oestrous cycle and the effect of betamethasone treatment.

Testosterone, oestradiol and progesterone were measured in peripheral plasma during the oestrous cycle of 6 heifers. Oestradiol and progesterone results confirmed earlier reports. Concentration of testosterone on the day of oestrus was 40+/-3 pg/ml (mean+/-S.E.M.), and two peaks were detected during the cycle, one 7 days before oestrus (1809+/-603 pg/ml) and the other (78+/- 7 pg/ml) on the day before the onset of oestrus. The concentration of progesterone declined in most cases 1 day after the maximum concentration of testosterone. Betamethasone treatment in 5 heifers extended luteal function by an average of 10 days: plasma androstenedione and oestradiol concentrations were unaltered; cortisol values were depressed for at least 16 days after treatment; testosterone concentrations were lowered by 13+/-2-4% during treatment, and except in one heifer the peak on Day -7 was abolished.

Adrenal Glands

Parturition in the goat: plasma concentrations of prostaglandin F and steroid hormones and uterine activity during late pregnancy and parturition.

Changes in plasma concentrations of hormones and uterine activity associated with spontaneous parturition in the goat were examined. No change in oestradiol-17beta concentration was detected during the experimental period, but oestradiol-17alpha consistently increased in concentration 3-4 days before parturition. This was followed by an increase in prostaglandin F two days later, while a pre-partum decline in progesterone concentration occurred 18-20 h after the significant increase in prostaglandin F. The onset of uterine contractions coincided with a significant decline in progesterone concentration and a period of continually rising prostaglandin F and oestradiol-17alpha concentrations. Uterine activity expressed in Montevideo units did not change until 10-8 h before foetal expulsion. These results support the hypothesis that in the goat the elevated prepartum concentration of prostaglandin F brings about luteolysis and a subsequent decline in progesterone concentration.

Animals

Mechanical properties of the ovine cervix during pregnancy, labour and immediately after parturition.

The stretch modulus (stress/strain) of strips of ovine cervical tissue in vitro was measured at different stages of gestation. A decrease in stretch modulus implies softening of the tissue. There was a gradual but progressive reduction in the stretch modulus with advancing pregnancy between 30 and 140 days gestation with a marked increase between 140 days gestation and the onset of labour (P less than 0.005). After the first trimester, the uterine end of the cervix was usually more distensible than the vaginal end. No further reduction in the stretch modulus of the cervix occurred between labour and delivery of the fetus. The results of this study suggest that while there is some softening of the ovine cervix during pregnancy, most of the softening takes place immediately prior to the onset of labour and delivery of the fetus.

Animals