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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 271 records · Page 15Linked to original sources
PubMed1983

Prolonged estrogen treatment induces changes in opiate, benzodiazepine and beta-adrenergic binding sites in female rat hypothalamus.

Exposure of the rat brain to estradiol is known to modify certain neurotransmitter binding sites. We have now examined the influence of long-term (3 months) treatment with this steroid. Opiate and benzodiazepine receptors are both elevated in hypothalamus but not in amygdala or cerebral cortex. In contrast, the affinity, but not maximum binding, of hypothalamic beta-adrenergic sites is reduced 5-fold. Our results confirm and extend previous reports that hypothalamic neurotransmitter binding sites are particularly sensitive to estrogen feedback.

Amygdala↗
PubMed1983

Treatment of the acute migraine attack--current status.

The main treatment of the acute migraine attack remains sleep, sedation, an anti-nauseant and analgesics, and in some patients 1 or 2 mg of ergotamine tartrate. Drugs containing large amounts of caffeine should not be used. Absorption of drugs may be impaired in a migraine attack. Metoclopramide is probably the anti-emetic of choice because it is an effective anti-nauseant and promotes normal gastrointestinal activity. Domperidone has a similar action but is said not to go through the blood-brain barrier, so is less likely to cause extrapyramidal reactions. All drugs, including analgesics such as aspirin and paracetamol, are best given in a soluble or effervescent form. Where vomiting occurs early in the attack, suppositories may be indicated. Ergotamine tartrate is necessary in about one third of attacks and is best given by suppository or by inhalation. Doses higher than 2 mg per attack or 6 mg in one week may cause toxic symptoms, the early signs of which are headache, nausea, vomiting and a feeling of not being very well. The non-drug treatments of an acute attack include pressing on the temporal artery, hot and cold compresses and relaxation.

Acetaminophen↗
PubMed1983

Photoperiodic modification of opiate but not beta-adrenergic or benzodiazepine binding sites in hamster brain.

Exposure to short photoperiods induces gonadal regression in the golden hamster. This is accompanied by a fall in serum gonadotropins and changes in hypothalamic neurotransmitter turnover. We have attempted to correlate these changes with alterations in neurotransmitter receptor binding parameters. Compared to hamsters held in long photoperiods, opiate ([3H] naloxone) binding in hamsters exposed to short photoperiods is elevated in whole brain and in cerebral cortex but not in hypothalamus. However, beta-adrenergic ([3H] dihydroalprenolol) and benzodiazepine ([3H] flunitrazepam) binding are unaffected in whole brain, cerebral cortex or hypothalamus. Thus, changes in hypothalamic noradrenaline turnover rate previously reported may not be correlated with changes in beta-adrenergic binding.

Alprenolol↗
PubMed1983

Increased arterial pressure variability after arterial baroreceptor denervation in fetal lambs.

Baroreceptor reflexes can be demonstrated during fetal life, but whether baroreceptors normally regulate fetal arterial pressure is unknown. This problem was addressed directly by measuring arterial pressure and analyzing its variation in eight unanesthetized fetal lambs throughout the last third of gestation, and comparing these data with similar measurements made in seven fetal lambs with denervated arterial baroreceptors. Measurements were made at 5-minute intervals over 24 hours in a total of thirty-three experiments. The coefficient of variation of mean arterial pressure (standard deviation of mean arterial pressure/mean value of mean arterial pressure) expressed as a percentage was used as an index of blood pressure variability. Coefficients averaged 7.0% in intact lambs and 12.1% in barodenervated lambs (P less than 0.001), signifying considerably increased variability of mean arterial pressure after barodenervation. Mean arterial pressure averaged over 24 hours was not different between the two groups prior to 120 days (0.8) of gestation. Between 120 days and term, mean pressure was significantly greater in the denervated fetuses (65 cm H2O) than in the sham-operated controls (60 cm H2O, P less than 0.025). These data demonstrate that a baroreceptor-blood pressure reflex functions during late gestational development in lambs and signify an important role of arterial baroreceptors in regulating fetal arterial pressure. Failure to regulate arterial pressure in the barodenervated fetus could result in significant alterations in placental perfusion and exchange, and in the regional delivery of oxygen and substrates to developing organs in these animals.

Animals↗
PubMed1983

Opiatergic control of LH secretion is eliminated by gonadectomy.

We have studied the stimulatory effects of naloxone and the inhibitory influence of the opiate peptide, FK 33-824, on LH secretion in the gonadectomized rat. Our results indicate that endogenous and exogenous opiate involvement in LH release disappear coincident with the removal of gonadal steroid feedback. At 7 days post-surgery naloxone is no longer able to stimulate LH secretion in male or female rats. Similarly, by 7 days in the male, and 21 days in the female, FK 33-824 is unable to inhibit LH secretion. We conclude that the coupling of hypothalamic opiate receptors to the LH regulatory mechanisms is dependent upon gonadal steroids. The most important of these appear to be estradiol and testosterone, since careful priming of long-term gonadectomized rats with these steroids is able to largely restore the LH responses to naloxone and FK 33-824.

Animals↗
PubMed1983

Opiatergic control of gonadotropin secretion during puberty in the rat: a neurochemical basis for the hypothalamic 'gonadostat'?

We have examined (1) the effects of naloxone and an opiate peptide, FK 33-824, on LH and FSH secretion in immature male and female rats and (2) the influence of sexual maturation on the ability of this peptide to inhibit LH secretion. FK 33-824 potently inhibits LH secretion in the 48-h-gonadectomized rat. This effect could be blocked by coinjection of naloxone, suggesting that the peptide exerts its influence through opiate receptors. An endogenous opiate component in the control of LH secretion was demonstrated by examining the effect of naloxone injection alone. Naloxone rapidly stimulated LH secretion in the intact or the acutely gonadectomized rat. Naloxone or FK 33-824 did not modify LHRH-stimulated release of gonadotropins from organ cultures of anterior pituitary obtained from immature rats. This suggests, in agreement with other reports, that naloxone or FK 33-824 controls LH secretion via a central, possibly hypothalamic site. We further observed a clear age-related reduction in LH sensitivity to FK 33-824 in the acutely (48-h) gonadectomized rat. Dose-response studies indicated a 4-fold reduction in opiate responsiveness in the 10 days preceding the first ovulation. Thus, the doses required to reduce serum LH levels by 50% are 0.03, 0.04, 0.16, and 0.17 mg/kg, respectively, for the groups 12, 23, 29, and 33 days of age. In the male, a similar change was noted when responsiveness was compared in pre- and postpubertal rats; 50% inhibition was achieved at 0.25, 0.89, and 0.88 mg/kg FK 33-824 for rats aged 26, 70, and 90 days, respectively. The shift in sensitivity to FK 33-824 is probably not due to a change in clearance rates, but this cannot be completely ruled out. Thus, our demonstration of a maturation-related reduction in opiate inhibition of LH suggests a critical role for endogenous (hypothalamic?) opiate peptides and opiate receptors in the onset of sexual maturation. Our results may also provide a neurochemical basis for the well described shift in hypothalamic sensitivity to gonadal steroids that occurs with the approach of puberty.

Animals↗
PubMed1982

Diethylstilbestrol regulates the number of alpha- and beta-adrenergic binding sites in incubated hypothalamus and amygdala.

Previous work has identified an effect of circulating estrogens on the number of central adrenergic binding sites. We have further characterized this effect by performing the experiments in vitro and have taken advantage of a well-described hypothalamic preparation in which diethylstilbestrol (DES), is known to elevate cAMP levels through a pathway which involves adrenoreceptors. We show that DES induces a reciprocal change in the numbers of alpha- and beta-adrenergic binding sites in incubated hypothalami obtained from intact immature female rats as well as from ovariectomized adult rats. The alpha-adrenergic binding sites are reduced by 25-30% whereas the beta-adrenergic sites are increased by 60-100%. The effect is maximal at 3 h in vitro (20 microM DES) and largely reversible following a 2 h wash in the absence of DES. Using the change in beta-adrenergic binding sites as a probe, we were further able to show that estradiol (100 microM) and 2-hydroxyestradiol (50 microM) had no effect. Further, the effect of DES was not blocked by the anti-estrogens clomiphene or tamoxifen. Since DES is able to elevate beta-adrenergic binding sites in hypothalamus and amygdala (brain areas known to contain high levels of estrogen receptors) but has no effect in cerebellum, we conclude that we have observed an effect of DES not shared by estradiol but which may be confined to estrogen target areas of the brain.

Amygdala↗
PubMed1982

beta-Adrenergic, but not benzodiazepine, binding sites are reduced in dystrophic mouse brain.

We have examined brain tissue from dystrophic mice (male 129/ReJ-dy and female 129 B6F1/J-dy) to determine whether CNS lesions may accompany the known muscular defects. In all brain regions examined we found a significant reduction in the numbers of beta-adrenergic binding sites when compared to brain from control mice. In contrast, the number of benzodiazepine binding sites appeared normal. These changes in adrenergic sites may be related to the known abnormally high excretion of catecholamines. Our results also emphasise the need to study extra-muscular sites in this disease.

Animals↗
PubMed1982

Migraine in children: a medical and psychiatric study.

Forty-seven migrainous children were examined medically, neurologically and psychiatrically and compared with matched controls from a dental clinic. One in six children suffered from more than one type of migraine. There was a wide variation in age of onset and the frequency and duration of attacks varied considerably. An "emotional upset" was the most frequently reported (86%) precipitating factor. Most children responded to simple therapeutic measures and detailed instructions about the timely use of medication. A significantly higher proportion of migrainous children than their controls showed signs of a neurotic disorder (mainly anxiety or depression) and had had a higher prevalence of neurotic disorder in the previous year. This increased prevalence was found to be associated with a disturbed parental relationship and certain factors related to their mothers (age, "malaise" score). A prospective study of an epidemiological sample based on systematic observation rather than recollections and opinions is likely to yield more conclusive results.

Adolescent↗
PubMed1982

Intestinal spirochaetosis: an electron microscopic study of an unusual case.

An unusual case of intestinal spirochaetosis is described. The rectum of a 34-year-old male, suffering from Crohn's disease and ankylosing spondylitis, was heavily infested by spirochaetes. Both absorptive and goblet cells were colonized. Spirochaetes were found not only on the luminal surface of these cells, but also within the cytoplasm, in occasional macrophages within the lamina propria and, even more surprisingly, within the occasional Schwann cell. The significance of these findings is discussed.

Adult↗
PubMed1982

Skeletal changes in preterm infants.

The skeletal changes in 19 very low birthweight infants (less than 1500 g) were observed from birth to 10 weeks, by means of clinical, biochemical, and radiological techniques. All infants were receiving a supplement of 800 IU vitamin D a day from age 2 weeks. None of the infants showed any specific physical sign of rickets during the period of study. Six infants showed radiological evidence of skeletal demineralisation; 1 of these had severe changes of rickets and 1 had both rickets and fractures. These 6 infants were of shorter gestational periods and lower birthweights than the infants not showing radiological changes. They tended to have more clinical problems and to reach a predetermined volume of feeds (160 ml/kg a day) later than the unaffected infants. Serum alkaline phosphatase values were significantly higher at 5 weeks in the infants with abnormal radiographs than in those without. There were no significant differences between the two groups in relation to serum calcium, inorganic phosphate, 25 hydroxyvitamin D, and immunoreactive parathyroid hormone. The pathogenesis of the skeletal lesions of very low birthweight infants remains unknown.

25-Hydroxyvitamin D 2↗
PubMed1982

Flunitrazepam binding sites in rat diaphragm. Receptors for direct neuromuscular effects of benzodiazepines?

The evidence for direct muscle relaxant effects of benzodiazepines is controversial. We now show that a crude membrane preparation of rat diaphragm possesses binding sites for [3H]flunitrazepam (FNZ). Scatchard analysis gave a binding site density of 1689 +/- 143 fmol/mg protein (Kd = 25.6 +/- 2.6 nM). These sites are of the "peripheral" type since clonazepam fails to displace [3H]FNZ as effectively as R05-4864 (IC50 values: 7.5 x 10(-6) M and 8 x 10(-9) M, respectively). Diazepam is almost as effective as R05-4864 and potently displaces [3H]FNZ binding (IC50 = 3 x 10(-8) M). We propose that the previously described effects of diazepam on rat diaphragm are mediated through high-affinity binding sites.

Animals↗
PubMed1982

A puberty-related attenuation of opiate peptide-induced inhibition of LH secretion.

The long-acting synthetic enkephalin FK 33-824 (FK) potently inhibits LH secretion in gonadectomized prepubertal male and female rats. The effect is reversible by coinjection of naloxone. We have observed an age-related decrease in the ability of FK to reduce LH secretion in the 48 h post-gonadectomized rat. Thus, the IC50 values (i.e. the dose required to give 50% reduction in LH levels) for 12, 23 and 33-day old female rats were 0.03, 0.04 and 0.17 mg/kg BW, respectively. The figures for pre- and post-pubertal male rats (ages 26 and 70 days) were 0.25 and 0.89 mg/kg BW, respectively. This attenuation of opiate-induced inhibition of LH release may provide a neurochemical basis for the well-described shift in sensitivity of gonadal steroid feedback which occurs with the approach of puberty.

Animals↗
PubMed1982

Investigation into the hypogonadism of the obese mouse (genotype ob/ob).

Features of the reproductive axis in the genetically hypogonadal, obese mouse (genotype, ob/ob) were examined at 5-8 months of age and compared with those of wild-type litter mates. Hypothalamic concentrations of dopamine and 5-hydroxytryptamine were normal. Those of 5-hydroxyindoleacetic acid, noradrenaline and LH-RH were raised. LH-RH was biologically active. Pituitary concentration of LH was normal, but that of FSH was raised. Serum concentrations of LH and FSH, compared with those of wild-type animals, were normal and low, respectively. Gonad and accessory sex organs weights were reduced. These findings suggest that the release of FSH but not LH is defective in the ob/ob mouse. Preliminary in-vitro experiments indicated that the pituitary gland responded normally or even supernormally towards LH-RH in its release of LH. The defect in the reproductive axis of the obese mouse may be due to inadequate release of LH-RH although an insensitivity of the pituitary gland towards LH-RH in its release of FSH cannot be excluded.

Animals↗
PubMed1982

Flurothyl-induced convulsions delay the onset of sexual maturation in the female rat.

We have investigated whether sexual maturation in female rats is affected by repeated flurothyl-induced convulsions. This treatment had no effect on the normal age-related increase in body weight though puberty (vaginal opening) was significantly delayed when compared with non-convulsed control rats. In an attempt to probe the mechanism of this delaying effect we observed that (1) anterior pituitary response to gonadotrophin releasing hormone in vitro was normal in terms of LH release but FSH secretion was impaired and (2) progesterone injection in oestrogen-primed convulsed rats failed to generate an ovulatory-type surge of LH or FSH. Basal serum levels and basal in-vitro secretion of LH and FSH were normal. We conclude that repeated convulsions adversely affect the hypothalamo-pituitary-gonadotrophin system of immature female rats.

Animals↗