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Biomedical subjects

C Austin

Publications and source records attributed to C Austin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hypoxia, metabolic inhibition, and isolated rat mesenteric tone: influence of arterial diameter.

The present study examined and compared the effects of severe hypoxia (induced by either substitution of O(2) in the gassing medium with N(2) or by addition of the O(2) scavenger sodium dithionite) and metabolic inhibition (induced by addition of sodium cyanide) on the tone of isolated rat mesenteric resistance vessels. The influence of vessel diameter and the endothelium on responses to these maneuvers was investigated. Hypoxia (due to both substitution of O(2) with N(2) and by addition of 2 mM sodium dithionite) caused near maximal relaxation of all tissues studied. Addition of 10 mM dithionite, however, produced a significantly smaller response. Two mM cyanide also relaxed mesenteric arteries. In small vessels a near maximal relaxation to cyanide was observed, however, in larger vessels the relaxation to metabolic inhibition was significantly less than that observed to hypoxia. Increasing the concentration of cyanide had no further effect on responses. All responses were found to be endothelium-independent. Thus, as the effects of hypoxia and cyanide are not always similar, care must be taken when extrapolating the effects of metabolic inhibition to those of hypoxia. The results of this study suggest that, in large mesenteric vessels at least, an "O(2) sensing step," in addition to effects of metabolism, may be involved in the hypoxic response.

Animals↗
PubMed2000

Mechanisms of 17 beta-oestradiol induced vasodilatation in isolated pressurized rat small arteries.

1. The influence of 17 beta-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 2. 17 beta-oestradiol caused rapid (t1.0 < 5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 microM. 3. The vasodilatory responses in both types of artery were unaffected by 10 microM L-nitro arginine (L-NNA) alone or in the presence of 10 microM indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). 4. Neither the oestrogen receptor antagonist ICI 182,780 (10 microM) nor the protein synthesis inhibitor cycloheximide (100 microM) had any effect on the responses of mesenteric arteries to 17 beta-oestradiol. 5. 17 alpha-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 beta-oestradiol. 6. Membrane impermeant 17 beta-oestradiol conjugated to bovine serum albumin (beta-oestradiol-17-hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. 7. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 beta-oestradiol. 8. These results taken together suggest that the acute effects of 17 beta-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane.

Androstadienes↗
PubMed2000

Fifteen years experience with an in-vitro fertilization surrogate gestational pregnancy programme.

The purpose of our study was to review and evaluate retrospectively the experience of an in-vitro fertilization (IVF) surrogate gestational programme in a tertiary care and academic centre. In a 15 year period from 1984 to 1999, a total of 180 cycles of IVF surrogate gestational pregnancy was started in 112 couples. On average, the women were 34.4 +/- 4.4 years of age, had 11.1 +/- 0.72 oocytes obtained per retrieval, 7.1 +/- 0.5 oocytes fertilized and 5. 8 +/- 0.4 embryos subsequently cleaved. Sixteen cycles (8.9%) were cancelled due to poor stimulation. Except for six cycles (3.3%) where there were no embryos available, an average of 3.2 +/- 0.1 embryos was transferred to each individual recipient. The overall pregnancy rate per cycle after IVF surrogacy was 24% (38 of 158), with a clinical pregnancy rate of 19% (30 of 158), and a live birth rate of 15.8% (25 of 158). When compared to patients who underwent a hysterectomy, individuals with congenital absence of the uterus had significantly more oocytes retrieved (P < 0.006), fertilized, cleaved and more embryos available for transfer despite being of comparable age. IVF surrogate gestation is an established, yet still controversial, approach to the care of infertile couples. Take-home baby rates are comparable to conventional IVF over the same 15 year span in our programme. Patients with congenital absence of the uterus responded to ovulation induction better than patients who underwent a hysterectomy, perhaps due in part to ovarian compromise from previous surgical procedures.

Adult↗
PubMed2000

Simultaneous monitoring of vascular contractility, intracellular pH and intracellular calcium in isolated rat mesenteric arteries; effects of weak bases.

We report the first simultaneous measurements of pHi, [Ca2+]i and tension, upon alteration of pHi, in isolated rat mesenteric arteries loaded with both carboxy SNARF and indo-1. In these vessels (pre-contracted by 30 mM KCl) alterations of pHi, by addition and subsequent washout of weak bases, produced complicated effects on tone. Although the changes in contractility did not mirror the changes in pHi they were, at all times, accompanied by parallel changes in [Ca2+]i.

Alkalies↗
PubMed2000

Subclavian deep vein thrombosis associated with the use of recombinant follicle-stimulating hormone (Gonal-F) complicating mild ovarian hyperstimulation syndrome.

OBJECTIVE: To describe two cases of subclavian deep vein thrombosis (DVT) associated with the use of recombinant gonadotropins and mild ovarian hyperstimulation syndrome (OHSS) and review the literature associated with this condition. DESIGN: Retrospective study (case report). SETTING: Tertiary academic IVF program. PATIENT(S): Two women undergoing IVF with intracytoplasmic sperm injection due to male factor infertility. INTERVENTION(S): Ovaluation induction with recombinant FSH, IVF, and therapeutic heparinization. MAIN OUTCOME MEASURE(S): Coagulation studies, resolution of DVT, delivery at term. RESULT(S): Mild OHSS with left subclavian thrombosis occurred in two patients. Laboratory evaluation revealed normal protein C, protein S, antinuclear antibodies (ANA), and absence of antiphospholipid (APA) and anticardiolipin antibodies (ACA). Antithrombin III levels and coagulation studies were also within normal limits. Both patients tested negative for a factor V Leiden mutation and delivered healthy infants at term. CONCLUSION(S): Arm swelling associated with the use of gonadotropins during controlled ovarian hyperstimulation should be promptly evaluated and treated. Subclavian vein thrombosis is a rare complication of ovulation induction, and the possibility that recombinant gonadotropins increase the risk for this complication should be further studied.

Adult↗
PubMed1999

Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a comparison with metabolic inhibition.

1. Hypoxia (PO2 < 5 mmHg) decreased vessel tone in isolated rat mesenteric arteries precontracted with either high [K+] or the thromboxane analogue U46619. This response was not altered by N-nitro-L-arginine (L-NA) and indomethacin. 2. Simultaneous measurement of pHi and tension showed that the decrease in vessel tone was accompanied by an intracellular acidification. Similar reductions in tone and pHi were observed with the metabolic inhibitors 2,4-dinitrophenol (DNP) and sodium azide. 3. The presence of the lactate transport inhibitor alpha-cyano-4-hydroxy-cinnamic acid (CHC) increased the magnitude of the acidification and resulted in a significantly faster reduction in tone in response to hypoxia. Addition of CHC to normoxic tissues caused both a vasodilatation and a reduction of pHi. 4. A decrease in pHi induced on washout of ammonium chloride (NH4Cl) resulted in an increase in tone. 5. Relaxation to hypoxia or metabolic inhibition was unaffected when the change in pHi was neutralized by addition of the weak base trimethylamine (TMA). 6. It is concluded that severe hypoxia decreases tone in isolated rat mesenteric arteries by a mechanism which is independent of nitric oxide and prostaglandins. Both severe hypoxia and metabolic inhibition reduced pHi, although this does not appear to be contributing to the changes in tone observed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Rat-2 fibroblasts express specific adrenomedullin receptors, but not calcitonin-gene-related-peptide receptors, which mediate increased intracellular cAMP and inhibit mitogen-activated protein kinase activity.

Rat-2 fibroblasts demonstrate specific binding of 125I-labelled rat adrenomedullin (KD=0.43 nM; Bmax=50 fmol/mg of protein) in the absence of 125I-labelled calcitonin-gene-related peptide (CGRP) binding. Therefore Rat-2 cells were used to examine the pharmacology and signal transduction pathways of adrenomedullin receptors. We examined the effects of adrenomedullin, the CGRP receptor antagonist CGRP-(8-37) and the amylin antagonists AC187 and AC253 on receptor binding and cAMP production. AC253, AC187 and CGRP-(8-37) inhibited 125I-adrenomedullin binding, with respective IC50 values of 25+/-8, 129+/-39 and 214+/-56 nM. Adrenomedullin dose-dependently increased intracellular cAMP (approximate EC50=1.0 nM). CGRP-(8-37), AC253 and AC187 antagonized adrenomedullin-stimulated cAMP production at micromolar concentrations. Using kinase-substrate assays, Mono Q FPLC and 'phospho-specific' Western blotting, we found that adrenomedullin alone abolished basal mitogen-activated protein kinase (MAPK) activity and dose-dependently inhibited platelet-derived-growth-factor-stimulated MAPK activity. Radioimmunoassay for adrenomedullin of media from Rat-2 cells showed a linear release of adrenomedullin-like immunoreactivity of 3.1 fmol/h per 2x10(6) cells. Gel-filtration chromatography showed that this adrenomedullin-like immunoreactivity co-eluted with synthetic rat adrenomedullin. Northern blotting with a rat adrenomedullin cDNA probe was used to confirm the presence of adrenomedullin mRNA. However, neither Northern blotting nor reverse transcriptase-PCR showed the presence of the cloned adrenomedullin receptor (L1). We conclude that the Rat-2 cell line expresses a specific adrenomedullin receptor (coupled to cAMP production and regulation of MAPK) and secretes adrenomedullin, which may participate in a regulatory control loop.

Animals↗
PubMed1999

Incipient left ventricular rupture complicating anomalous left coronary artery.

A 4-month-old girl presented with 2 weeks of symptoms and physical signs of heart failure. Echocardiography demonstrated marked left ventricular dilation, thinning of the myocardium with anterolateral akinesis, mitral regurgitation, a moderate pericardial collection, and an anomalous left coronary artery from the pulmonary artery. At operation there was a tense hemopericardium and a site of imminent rupture through a transmural anterior infarction. The anomalous artery was reimplanted in the ascending aorta, and an extensive infarct resection and ventricular repair performed. Support with a left ventricular assist device was required for 3 days, but the infant subsequently made a satisfactory recovery. Left ventricular rupture is a very rare complication of this lesion, but should be considered if there is evidence of a pericardial collection.

Coronary Vessel Anomalies↗
PubMed1998

Lineage analysis using retroviral vectors.

Knowledge of the genealogical relationships of cells during development can allow one to gain insight into when and where developmental decisions are being made. Genealogical relationships can be revealed by a variety of methods, all of which involve marking a progenitor cell and/or a group of cells and then following the progeny. The use of replication-incompetent retroviral vectors for the analysis of lineal relationships in developing vertebrate tissues is described. An overview of the relevant aspects of the retroviral life cycle is given, and the strategies and current methods in use in our laboratory are described.

Animals↗
PubMed1998

A review of the actions and control of intracellular pH in vascular smooth muscle.

OBJECTIVE: This review is an account of the physiological issues involved in the effects of pH on vascular smooth muscle tone. The following criteria were considered when reviewing the literature: (i) the type of smooth muscle, i.e. either tonic or phasic, (ii) the source of the smooth muscle i.e. pulmonary, systemic, large artery, resistance artery, vein or cell line, (iii) the effects of changing intracellular or extracellular pH alone, (iv) the acute or chronic effects of altered pH (v) the influence of extracellular pH on intracellular pH and (vi) the influence of altered intracellular pH on basal or agonist induced tone. Studies of the effects of pH on the individual intracellular components of vascular tone, specifically sarcoplasmic reticulum and contractile proteins function are considered. Finally, the pH sensitivity of molecular components that contribute to smooth muscle cell tone are reviewed. CONCLUSIONS: There appear to be distinct differences in the response of large arteries and resistance arteries to altered intracellular pH which may be based on the different properties of the smooth muscle within the wall of each blood vessel. Similarly, systemic and pulmonary vessels may respond differently, but no systematic study exists to allow a more definitive conclusion. Factors controlling intracellular pH such as intracellular buffering power and sarcolemmal pH regulating mechanisms may differ across the vascular bed and may contribute to some of the differences observed in response to altered extracellular pH. Finally, few studies have examined the pH sensitivity the intracellular processes involved in basal tone and pharmaco-mechanical coupling in vascular smooth muscle. More information concerning these latter aspects of smooth muscle function is required to progress the understanding of the modulator action on pH on vascular tone.

Arteries↗
PubMed1998

Effects of 17beta-oestradiol on rat isolated coronary and mesenteric artery tone: involvement of nitric oxide.

Pre- and post-menopausal women receiving oestrogen replacement therapy have a significantly reduced risk of cardiovascular disorders. It has been suggested that this protection might be partly a result of a direct relaxant effect of oestrogens on coronary arteries. This study examines and directly compares the effects of 17beta-oestradiol on rat isolated coronary and mesenteric vessels. The influence of nitric oxide on these responses was also investigated. 17Beta-oestradiol caused similar concentration-dependent relaxation of isolated coronary and mesenteric resistance arteries pre-contracted with either KCl (60 mM) or 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin (U46619; 1 microM). The relaxation responses to 17beta-oestradiol were significantly reduced, but not totally inhibited, in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; they were not altered by indomethacin, an inhibitor of prostaglandin synthesis. The responses to 17beta-oestradiol in the presence of L-NAME were not dependent on the vessel studied or the pre-contracting agent used. These results suggest that nitric oxide might contribute to the vasodilatory effects of 17beta-oestradiol in rat isolated coronary and mesenteric resistance arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Evaluation of predictive factors for multiple pregnancies during gonadotropin/IUI treatment.

PURPOSE: Our purpose was to analyze factors for their predictability of multiple pregnancies in patients treated with a combination of human menopausal gonadotropins (hMG) and intrauterine insemination (IUI). METHODS: The records of all patients conceiving through treatment with hMG/IUI were reviewed for factors predictive of multiple pregnancy. RESULTS: Ninety-one pregnancies reviewed included 78 singleton (86%), 8 twin (9%), and 5 higher-order pregnancies (5%). The total number of follicles > 10 mm was greater in the multiple-pregnancy group and there was a decreased number of postwash sperm in the multiple-pregnancy group. Otherwise there was no significant difference in the factors analyzed. CONCLUSIONS: No factor or combination of factors predicts multiple pregnancies to a degree that it would be helpful in managing or counseling patients.

Female↗