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Biomedical subjects

C Docherty

Publications and source records attributed to C Docherty.

10 recordsLinked to original sources
PubMed2003

Life before birth: effects of cortisol on future cardiovascular and metabolic function.

UNLABELLED: The concept of fetal programming is an area that is now under rigorous investigation in many laboratories throughout the world. We need to engender a fascination in all segments of society, not just pregnant women, about life in the womb. CONCLUSION: Everyone needs to understand that improving the condition of the fetus will have personal, social and economic benefits. The time has come to realize that, in a sense, it is not just women who are pregnant but it is the family and the whole of society.

Animals↗
PubMed1999

A comparative study of vascular responsiveness of myometrial and omental small resistance arteries in late-gestation sheep.

OBJECTIVE: We determined whether local regulation by vasoactive agents differs in the myometrial and omental vascular beds in the pregnant sheep. Specifically, we hypothesized that there would be blunting of in vitro responses to constrictor agonists, enhancement of sensitivity to dilator agonists, or both in myometrial compared with omental resistance arteries. STUDY DESIGN: We compared in vitro responsiveness of small resistance intramyometrial and omental arteries from near-term pregnant ewes to the vasoconstrictor agents norepinephrine, U46619 (a thromboxane sympathomimetic), and potassium and the vasodilator agents acetylcholine and bradykinin. RESULTS: The vascular sensitivity and the maximum response of intramyometrial small arteries to U46619 was attenuated compared with that of omental arteries. There were no significant differences between the intramyometrial and omental arteries in response to norepinephrine, potassium, acetylcholine, or bradykinin. CONCLUSIONS: These results support regional heterogeneity of regulation of function in different maternal vascular beds during pregnancy. The relative insensitivity of the myometrial arteries to the thromboxane mimetic indicates the existence of decreased constrictor function that may facilitate preservation of uterine blood flow in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Endothelin receptors mediating contraction of rat and human pulmonary resistance arteries: effect of chronic hypoxia in the rat.

1. We examined the endothelin (ET) receptors mediating contractions to ET-1, ET-3 and sarafotoxin S6c (SX6c) in rat pulmonary resistance arteries by use of peptide and non-peptide ET receptor antagonists. Changes induced by pulmonary hypertension were examined in the chronically hypoxic rat. The effect of the mixed ET(A)/ET(B) receptor antagonist SB 209670 on endothelin-mediated contraction was also examined in human pulmonary resistance arteries. 2. In rat vessels, the order of potency for the endothelin agonists was SX6c = ET-3 > ET-1 (pEC50 values in control rats: 9.12+/-0.10, 8.76+/-0.14 and 8.12+/-0.04, respectively). Maximum contractions induced by ET-3 and ET-1 were increased in vessels from chronically hypoxic rats. 3. The ET(A) receptor antagonist FR 139317 (1 microM) had no effect on the potency of ET-1 in any vessel studied but abolished the increased response to ET-1 in the chronically hypoxic vessels. The ET(A) receptor antagonist BMS 182874 (1 microM) increased the potency of ET-1 in control rat vessels without effecting potency in the pulmonary hypertensive rat vessels. 4. Bosentan (non-peptide mixed ET(A)/ET(B) receptor antagonist) increased the potency of ET-1 in control rat vessels but was without effect in the pulmonary hypertensive rat vessels. Bosentan (1 microM) inhibited responses to SX6c in control and chronically hypoxic rat vessels with pKb values of 5.84 and 6.11, respectively. The ET(B) receptor antagonist BQ-788 (1 microM) did not inhibit responses to ET-1 in any vessel tested but did inhibit responses to both SX6c and ET-3 (pKb values in control and chronically hypoxic rat vessels respectively: SX6c 7.15 and 7.22; ET-3: 6.68 and 6.89). BQ-788 (1 microM) added with BMS 182874 (10 microM) did not inhibit responses to ET-1 in control vessels but caused a significant inhibition of responses to ET-1 in chronically hypoxic preparations. 5. SB 209670 inhibited responses to ET-1 in both control and chronically hypoxic vessels with pKb values of 7.36 and 7.39, respectively. SB 209670 (0.1 and 1 microM) virtually abolished responses to ET-1 in the human pulmonary resistance artery. 6. In conclusion, in rat pulmonary resistance arteries, vasoconstrictions induced by ET-1, SX6c and ET-3 are mediated predominantly by activation of an ET(B)-like receptor. However, lack of effect of some antagonists on ET-1 induced vasoconstriction suggests that ET-1 stimulates an atypical ET(B) receptor. The increase in potency of ET-1 in the presence of some antagonists suggests the presence of an inhibitory ET(A)-like receptor. The influence of this is reduced, or absent, in the chronically hypoxic rats. Increased responses to ET-1 are observed in the chronically hypoxic rat and may be mediated by increased activation of ET(A) receptors. SB 209670 is unique in its potency against responses to ET-1 in both control and chronically hypoxic rats, as well as human, isolated pulmonary resistance arteries.

Animals↗
PubMed1998

Development of endothelin receptors in perinatal rabbit pulmonary resistance arteries.

1. Contractile responses to endothelin-1 (ET-1) and sarafotoxin S6c (S6c) were studied in pulmonary resistance arteries (approximately 320 microm i.d.) from fetal, 0-24 h, 4 day and 7 day rabbits. The effects of the ET(A)-selective antagonist FR139317, the selective ET(B) receptor antagonist BQ-788 and the non-selective ET(A)/ ET(B) receptor antagonist SB 209670, on these responses, were determined. Acetylcholine-induced vasodilation and noradrenaline-evoked contractions were also examined. 2. ET-1 potency was in the following order (pEC50 values): fetal (8.7) = 0-24 h (8.8) = 4 day (8.6) > 7 day (8.0). The order of potency for S6c was 7 days (11.1) = 4 days (10.8) > 0-24 h (9.7) > fetal (8.6). Hence, S6c and ET-1 were equipotent in the fetus but S6c was increasingly more potent than ET-1 with increasing age, being some 1000 times more potent by 7 days. By 7 days, responses to ET-1 were also resistant to both FR139317 and BQ-788. FR139317 inhibited responses to ET-1 in vessels from 0-24 h and 4 day, but not fetal, rabbits (pKb: 6.4 in 4 day rabbits). BQ-788 inhibited responses to ET-1 at all age points except for 7 days (pKb: 6.7 at 0-24 h; 6.2 at 4 days). BQ-788 inhibited responses to S6c at all age points (pKb: 8.5 at 4 days). SB 209670 inhibited responses to ET-1 and S6c at 0-24 h and 4 days (pKb for ET-1: 8.3 and 8.0 respectively; pKb for S6c: 9.2 and 10.2 respectively). 3. Acetylcholine (1 microM) induced vasodilation at all age points (inhibited by 100 microM L-N(omega)-nitroarginine methylester) although the degree of vasodilation was significantly reduced (approximately 75%) at 0-24 h. Noradrenaline induced contraction at all age points except 7 days and its response was significantly enhanced at 0-24 h. 4. Over the first week of life, the potency of S6c increases whilst that to ET-1 decreases suggesting differential development of responses to ET-1 and S6c and heterogeneity of ET(A)- or 'ET(B)-like' receptor-mediated responses. There is no synergism between ET(A) and ET(B) receptors at birth but this is established by 7 days. Immediately after birth rabbit Pulmonary Resistance Arteries are hyperresponsive to ET-1 and noradrenaline but exhibit impaired nitric-oxide dependent vasodilation.

Acetylcholine↗
PubMed1987

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Animals↗
PubMedDate not supplied

Predictors of outcome in a short-term psychiatric day hospital program.

This study assessed selected chronicity, social support, and personality variables as predictors of outcome in a 3-week psychiatric day hospital program. Measured outcome included pre- and post-treatment scores on the BDI, STAI, and SCL-90-R from 224 patients. A single outcome variable based on the average standardized residual changes scores for these measures was derived to assess whether symptom severity at discharge was greater or less than predicted. Predictor variables were analysed using multiple regression. Chronicity variables predicted outcome, with patients hospitalized more than once and those with personality disorders more symptomatic than expected after treatment. Social support and personality variables failed to predict outcome; however, patients who scored higher on the MMPI Si scale were more symptomatic than expected at discharge. Although these results possess marginal clinical utility in terms of accounting for symptom change variation, this study overcame some methodological difficulties seen in prior day hospital literature. Future research should consider a prospective approach, including random treatment assignment, comprehensive and diverse outcome measures, and exploration of specific diagnostic groups.

Adult↗
PubMedDate not supplied

The nurse lecturer's role in mentoring the mentors.

AIM: This article reports on the results of a survey conducted early in 1999 investigating the effectiveness of current arrangements for mentor preparation and ongoing mentor support provided within adult placement areas within Greater Glasgow Health Board. METHOD: A sample of 150 mentors was surveyed with a response rate of 47 per cent (n = 71). RESULTS: Results indicate that although mentors are generally satisfied with the current approach to mentorship preparation, the issue of support from both managers and academic staff is problematic. CONCLUSION: Respondents indicated that they wished to see lecturers visiting the practice placement areas and providing support, particularly in relation to assessment of students. Also highlighted in this study is the need for more effective communication between placement areas and academic staff.

Attitude of Health Personnel↗