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Biomedical subjects

B K Evans

Publications and source records attributed to B K Evans.

At least 19 recordsLinked to original sources

Evidence for direct vasoconstrictor activity of melatonin in "pressurized" segments of isolated caudal artery from juvenile rats.

Responses of isolated, 60 mmHg 'pressurized' segments of the distal caudal artery of adult and juvenile Wistar rats to melatonin and the selective alpha 2-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304) were examined using the Halpern pressure myograph. Melatonin showed no direct vasoconstrictor activity in vessels from adult rats, whereas UK-14304 produced moderate vasoconstriction (pD2-7.43 +/- 0.09). In the presence of phenylephrine-induced tone, melatonin produced a variable but small constrictor response (less than 10 microns reduction in diameter) in some vessels; the response to 1 mumol/l UK-14304 was less than in the absence of tone. In vessels isolated from juvenile rats, melatonin caused concentration-dependent vasoconstriction with a maximum response about 70% of the maximum response elicited by UK-14304. Vessels from juvenile rats were more sensitive to melatonin (pD2-9.40 +/- 0.07) than they were to UK-14304 (pD2-8.12 +/- 0.14). In the presence of phenylephrine-induced tone, the vasoconstrictor responses to both melatonin and IK-14304 were markedly less; the sensitivity to melatonin was not different from that seen in the absence of tone. These findings indicate that 'pressurized' segments of the isolated distal caudal artery may provide a simple and convenient, functional model of melatonin receptors. The findings also appear to implicate melatonin in thermoregulatory processes in juvenile rats.

Aging

A pharmacokinetic study of sulphasalazine and two new formulations of mesalazine.

We have examined the pharmacokinetics of enteric coated sulphasalazine compared with two new formulations of mesalazine. These consisted of microgranules of mesalazine coated with Eudragit S in a concentration of either 20 or 25% dry lacquer substance; these in turn were enclosed in capsules coated with Eudragit L. In-vitro dissolution studies of coated microgranules showed that drug release was pH dependent. Studies in 7 normal volunteers showed median peak concentrations of 5-amino-salicylic acid and N-acetyl-5-amino-salicylic acid occurred at about 6 hours with both microgranular preparations, compared with sulphasalazine at 15 h. The microgranule formulation coated with 20% Eudragit S gave serum levels and overall systemic absorption similar to values with sulphasalazine. This new formulation may be of value for delivering mesalazine and other therapeutic agents to the colon.

Adult

Duchenne's muscular dystrophy: review and recent scientific findings.

In this brief review, we describe the clinical manifestations of Duchenne's muscular dystrophy (DMD) and other similar syndromes, outline the history of the dystrophin gene's identification and its relationship to these muscular dystrophies, and relate the importance of the gene's discovery to clinical neurology. We do not discuss treatment.

Animals

Tripotassium dicitrato bismuthate enemas in the treatment of ulcerative proctitis.

Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.

Adult

Paraneoplastic motor neuron disease and renal cell carcinoma: improvement after nephrectomy.

A 74-year-old man had a paraneoplastic motor neuron disease mimicking amyotrophic lateral sclerosis. He had an elevated erythrocyte sedimentation rate, other laboratory abnormalities, and a previously undiagnosed renal cell carcinoma. Four months after nephrectomy, his strength had improved and he had no fasciculations. Seven other patients with cancer and motor neuron disease improved or stabilized after tumor treatment. Even though it is rare, paraneoplastic motor neuron disease is important to diagnose because it may be treatable.

Aged

Quantitative structure--activity relationships and carminative activity II: steric considerations.

The unexplained variation in the relationships between carminative activities and octanol--water distribution coefficients of various classes of compounds was explained. The steric substituent constant (Es) value, van der Waals volume, and molecular connectivity were introduced into a previously derived correlation. Each parameter brought about an improvement, and molecular connectivity was the most successful. Correlations containing molecular connectivity was the most successful. Correlations containing molecular connectivity terms explained the excess variation. The results were in agreement with a mechanism in which carminative activity depended on the availability of the oxygen atom in the functional group of the molecule and was reduced when the substituent attached to the oxygen hindered the interaction between the oxygen atom and the receptor.

Animals

Reinnervation following guanethidine-induced sympathectomy of adult rats.

The reinnervation of various tissues by autonomic neurons has been studied in adult rats which had been sympathectomized by chronic guanethidine treatment (30 or 60 mg/kg/day for 8--15 weeks). In the heart, iris, ileum, mesentery, vas deferens and epididymis, fluorescence histochemistry reveals an almost complete disappearance of adrenergic fibres which is very longlasting. Even after 63 weeks few fluorescent fibres can be seen in these tissues and the density of innervation is not increased by incubation in alpha-methylnoradrenaline. The superior cervical ganglion represents an exception; large numbers of fluorescent fibres but few fluorescent ganglion cells were apparent during recovery. Axon counts carried out by electron microscopy on the vas deferens showed that after recovery for one year the number of axons was similar to that of controls; however, the pattern of innervation was abnormal, small granular vesicles were rarely seen and there was little uptake of 5-hydroxydopamine. On the basis of this evidence and of some pharmacological data it is suggested that there is a limited reinnervation by adrenergic axons accompanied by a great increase in the number of non-adrenergic, possibly cholinergic, axons.

Animals

Chronic guanethidine treatment of female rats including effects on the fetus.

Adult virgin female rats were injected daily with low doses (5 or 10 mg/kg) or a high dose (30 mg/kg) of guanethidine for 12 or 18 weeks respectively. 'Short' and 'long' noradrenergic neurones were unaffected by low doeses. This contrasts markedly to earlier findings in male rats in which long-term damage of 'short' noradrenergic neurones occurred, and indicates a basic difference between 'short' noradrenergic neurones in male and female rats. Widespread degeneration of both types of neurones followed treatment with high doses and little reinnervation was observed 8 weeks after cessation of treatment. Fertility, pregnancy and litter size were apparently unaffected. Some teratogenic effects were observed in the offspring of female rats treated with guanethidine (10 or 25 mg/kg/day) before and throughout pregnancy. However, these effects had largely disappeared by the time the offspring were 10 weeks old. Since noradrenergic neurones of newborn rats are particularly sensitive to damage by guanethidine it would appear that either very little guanethidine crosses the placental barrier or that noradrenergic neurones are not susceptible during prenatal development to the cytotoxic effects of guanethidine.

Adrenergic Fibers

Influence of neuronal activity levels on the cytotoxic effects of guanethidine.

Reduction of activity levels in the noradrenergic innervation of the iris of the rat by decentralization of the superior cervical ganglion resulted in a marked increase in sensitivity of these fibers to damage by chronic guanethidine treatment (15 mg/kg/day) as shown by fluorescence histochemistry. Guanethidine also had an increased cytotoxic effect on the decentralized nerve cell bodies. These results suggest that the relative inactivity of male "short" noradrenergic neurons may contribute to their sensitivity to damage by guanethidine. The nature of the damage produced in other tissues by this dose of guanethidine indicates that levels of neuronal activity are not the only factor determining sensitivity to the cytotoxic effects of this drug.

Animals

Quantitative structure-activity relationships and carminative activity.

Carminative activities of 34 alcohols, esters, ethers, phenols, and carbonyl compounds were determined using the guinea pig isolated ileum preparation and are expressed as the ability to produce a 50% inhibition (ID50) of a standard response to carbachol. Aqueous solubilities were measured at 37 degrees using either UV absorption or GLC. The ratios of solubility to ID50 were reasonably constant, suggesting nonspecific biological activity, similar to that previously observed with general anesthetics. Hansch analysis indicated that carminative activities were largely controlled by solubility, as indicated by octanol-water distribution coefficients. The principal remaining factor appeared to be the steric availability of the oxygen atom in the functional group of the compound.

Animals

Effects of chronic bretylium treatment on the sympathetic neuron and the smooth musculature of the rat.

The effects of chronic i.p. injection of high doses of bretylium on sympathetic nerves on the smooth musculature of the vas deferens of adult and newborn rats were examined using fluorescence histochemistry, light and electron microscopy and organ bath physiological techniques. Bretylium treatment caused mitochondrial swelling, loss of cristae and the formation of electron-dense inclusions in the mitochondria of sympathetic neurons. However, neuron degeneration was not observed and fluorescent histochemical appearance of adrenergic neurons was normal. A small transient supersensitivity of the isolated vas deferens of bretylium-treated rats to noradrenaline, but not to acetylcholine, occurred. There was, however, considerable increase in the maximal contractile response to both noradrenaline and acetylcholine. In high calcium concentrations acetylcholine-induced contractions of vasa deferentia from bretylium-treated rats were significantly greater than control; there was no difference in magnitude of noradrenaline-induced contractions.

Acetylcholine

Intracranial injections of 6-OHDA. Comparison of catecholamine-depleting effects of different volumes and concentrations.

Fluorescence histochemistry was used to assess monoamine depletion after injections of 6-OHDA into selected brain areas. Two volumes (2 and 4 mul) and 4 concentrations (1, 2, 4 and 8 mug/mul) of 6-OHDA were injected into the olfactory tubercle, the posterior lateral hypothalamus and the lateral hyopthalamus. Selective destruction of catecholamine-containing neurons resulted from all injections of 6-OHDA with the exception of the 2 lowest doses (2 and 4 mul of 1 mug/mul) and the highest dose (4 mul of 8 mug/mul) which produced nonspecific damage of brain parenchyma. The results indicate that, in addition to the selection of an effective dose, it is also possible to choose a site of injection which will produce a maximal area of specific depletion. In cases where injections into terminal areas caused limited specific depletion the same dose injected into preterminal axons often caused a more widespread loss of fluorescence. With volume, concentration and anatomical location being important variables to consider, caution is needed in the interpretation of behavioural experiments. When using 6-OHDA it is necessary to show that specific depletion of catecholamines has been achieved.

Animals