Biomedical subjects
Publications and source records attributed to M G Briscoe.
Near space and time coincident 200-kHz acoustic backscatter and CTD measurements were taken during an interdisciplinary study of the internal wave packets that propagate through Massachusetts Bay. The data strongly support the contention that acoustic wavefields can be backscattered from turbulent mixing events (microstructure) associated with the internal wave packets.
The Self-Inflicted Injury Severity Form (SIISF) was developed as an epidemiological research tool for identifying individuals in hospital emergency departments who have life-threatening self-inflicted injuries. Data were collected from 715 patients with self-inflicted injuries in two large hospitals. In 295 of these cases, a second set of data was independently collected for assessment of interrater reliability. Validity was assessed by comparing the SIISF results with simultaneously collected Risk-Rescue Ratings. Assessment of interrater reliability found that only 2.4% of physicians disagreed on the suicide method used. The kappa statistic for method used was .94, indicating excellent agreement. The SIISF was found to distinguish between severe and less severe injuries. Thus, it appears to provide a simple method to distinguish patients who have life-threatening self-inflicted injuries.
The thermogenic action of beta-adrenoceptor agonists may be due, in part, to increased metabolism in skeletal muscle. Previous results suggest that vasoconstriction is also necessary, and that the effect can be blocked by vasodilators. Both noradrenaline and the beta-3 agonist, ICI D7114, were studied using two dog hindlimb protocols. During constant perfusion conditions, ICI D7114 caused a significant increase in hindlimb oxygen consumption although it is a vasodilator. Noradrenaline resulted in a smaller rise in oxygen consumption, and produced a marked vasoconstriction. Both noradrenaline and ICI D7114 resulted in decreased oxygen consumption when the blood flow was allowed to vary in response to the drug treatment. The results suggest that changes in tissue oxygen consumption caused by beta-agonists are not related to vasomotion.
Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these species and is replaced by a tissue with the gross characteristics of white adipose tissue. Here we provide evidence that treatment of adult dogs with a beta 3-adrenergic receptor agonist (ICI D7114) that has thermogenic and antiobesity properties leads to the appearance of BAT at several anatomical sites. The presence of BAT was primarily demonstrated by monitoring the inner mitochondrial membrane uncoupling protein and its mRNA, which are unique to the tissue. Neither message nor protein was detected in adipose tissue samples from control dogs but both were detected in samples from dogs treated with ICI D7114. The data suggest that stimulation of beta 3-adrenergic receptors can reactivate nascent BAT (which has the appearance of white adipose tissue) by increasing expression of the gene coding for uncoupling protein or lead to the recruitment of fully differentiated BAT from preadipocyte precursor cells.
1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosphate (GDP)-binding (ED50, 0.15 mg kg-1, p.o.) with no chronotropic effects on the heart at these doses. 2. Reference beta-adrenoceptor agonists, isoprenaline and clenbuterol, also stimulated oxygen consumption and BAT activity but were less selective because they also produced effects on heart rate at these doses. 3. Treatment of conscious rats with ICI D7114 did not attenuate the chronotropic effects on the heart of a subsequent isoprenaline challenge. 4. Administration of ICI D7114 or of its acid metabolite had no effect in a cat soleus muscle model of tremor or on blood potassium levels in the conscious dog, indicating lack of effects at beta 2-adrenoceptors. 5. The results indicate that ICI D7114 may have activity at atypical beta-adrenoceptors in brown adipose tissue leading to increased whole body oxygen consumption.
We have previously reported that the negative inotropic effects of both verapamil and nifedipine on cat papillary muscles are enhanced as pH is lowered from 7.4 to 6.8 and 6.0. These studies have now been extended to compare the relative sensitization by acidosis of verapamil, nifedipine, lidoflazine, perhexilene and diltiazem. Developed tension was recorded in cat papillary muscles and the calcium concentration was adjusted over the range 2 to 10 mM. At pH 7.4, addition of all five drugs moved the dose response curve to the right with pA2 values from 4.82 (lidoflazine) to 9.94 (nifedipine). At pH 6.0, there was eight-fold sensitization by acidosis for verapamil, but four, three, and two-fold sensitization for nifedipine, lidoflazine and perhexilene. Diltiazem, however, was not sensitized by acidosis. The differential effects of acidosis on the negative inotropic properties of the five drugs may reflect their ancillary properties opposite gating of the calcium channel, local anaesthesia, intracellular calcium movement or Na+/Ca2+ exchange, but also suggest that diltiazem may have the property of inhibiting the effects of low pH on cell membranes.
The interactions between ICI 118, 587 (Corwin) a beta 1-selective partial adrenergic agonist, and atenolol (Tenormin), propranolol (Inderal) and verapamil were examined first in anaesthetised dogs pretreated with syrosingopine and vagotomised. ICI 118, 587 was administered iv in cumulative doses of 0.1 to 1000 micrograms X kg-1. In four animals, heart rate increased from 102 +/- 4 to 188 +/- 12 beats X min-1 with a KA of 2.5 +/- 0.9 micrograms X kg-1. ICI 118, 587 was then administered to five groups each of four animals pretreated with atenolol (250 micrograms X kg-1 and 500 micrograms X kg-1iv), propranolol (250 micrograms X kg-1 and 500 micrograms X kg-1) or verapamil (200 micrograms X kg-1 plus 5 micrograms X kg-1 X min-1 iv). Both atenolol and propranolol shifted the dose response curve to the right but verapamil did not. Atenolol did not lower the maximal heart rate response to ICI 118,587. Both propranolol and verapamil slowed heart rate significantly (P less than 0.05) after, but not before, ICI 118,587. Further studies were then carried out in vitro. Cat papillary muscles were superfused with physiological saline at pH 7.4 and with either atenolol or ICI 118,587 at 5 X 10(-5) mol X litre-1. Tension was recorded at Lmax over a [Ca2+] range of 0.5 to 8 X 10(-3)mol X litre-1. The pA2 for verapamil against Ca2+ in the presence of atenolol and ICI 118,587 was 5.25 +/- 0.10 and 6.57 +/- 0.22 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of acidosis on the myocardial sensitivity to verapamil and nifedipine were examined by measuring the changes in tension in cat papillary muscles perfused in oxygenated physiological saline. Calcium concentration was altered over a range of 2 to 12 mmol . litre-1 and pH adjusted to 7.4, 6.8 or 6.0. Addition of verapamil or nifedipine moved the calcium dose response to the right. At pH 7.4 a Schild plot confirmed competitive interaction between verapamil and calcium, with a calculated dissociation constant (KB) for verapamil of 4.6 +/- 0.2 micrograms . cm-3. At pH 6.0 the slope was less than 1.0 (not significant, P = 0.2) but KB was significantly lower (P less than 0.01) at 0.62 +/- 0.4 microgram . cm-3. Similar enhancement of sensitivity by lowered pH was found for nifedipine. It is proposed that partial inhibition of the slow channel by acidosis increases the sensitivity to calcium entry blockers. This might create a differential effect between normal and diseased tissue in vivo.
The changes in tension with increasing calcium concentration were examined in papillary muscles isolated from cats, rabbits, and rats, and in isolated rat atria. Similar curves were determined for cat femoral artery and lower descending aorta from rabbits and rats. In all tissues, the concentration of verapamil (KB) was determined which achieved a calcium dose ratio of 2. Rat myocardium was the most (KB = 3.38 +/- 0.18 X 10(-6) mol . litre-1) and rabbit the lest (KB = 1.18 +/- 0.01 X 10(-5) mol . litre-1) sensitive to verapamil. Cat tissue was intermediate; rat atria and ventricle were similar. By contrast, arterial sensitivity was always greater with arterial-myocardial sensitivity ratios varying from 175 +/- 7 in the cat to 1073 +/- 97 in the rabbit. This technique is a formal evaluation of the arterial-myocardial sensitivity of calcium entry blockers and may permit prediction of the myocardial and vasodilator properties of novel compounds.
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Optimal conditions for cryopreservation of nematode larvae have been established using Nematospiroides dubius. Ruminant nematode larvae were infective up to three and a half years after freezing if introduced by laporotomy (intestinal nematodes) or by oral challenge (abomasal nematodes). The advantages of cryopreservation over normal storage of larvae are discussed.
In sheep, 3-tert butyl 4'5 dicyano 6 methyl 2' bromo salicylanilide was found to be active against mature Fasciola hepatica down to 0.2 mg/kg but was toxic at 1.5 mg/kg.
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