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Biomedical subjects

C A Wilson

Publications and source records attributed to C A Wilson.

At least 199 records · Page 11Linked to original sources

Gastrointestinal absorption of the strongly acidic drug proxicromil.

Gastrointestinal absorption of the strongly acidic drug proxicromil has been studied with respect to its physical organic chemistry. The lipophilicity of the drug above pH 6 in octanol-buffer partition experiments is dependent on ion pair formation. Similar trends were demonstrated for the in vitro partition of the compound into GI tissue. The absorption of the compound from the perfused GI tract of rats in vivo was not consistent with classical un-ionized drug absorption theories and indicated the operation of other processes, especially ion pair formation, as major mechanisms of proxicromil absorption.

Animals↗

Hormonal control of carbonic anhydrase III.

Using radioimmunoassay, the concentration of carbonic anhydrase III (CA III) in the livers of adult male rats was found to be approximately 30 times greater than that observed in mature females. Castration of male rats led to a marked reduction in liver CA III concentrations that could be partially restored to control levels by testosterone replacement. Administration of testosterone to ovariectomized female rats induced about a 5-fold increase in liver CA III concentration. Immunoprecipitational analysis of the products of liver mRNA translation in vitro with antiserum specific for CA III showed that hormonal control of the levels of CA III in rat liver is mediated by changes in the amount of translatable CA III mRNA. Marked changes in liver CA III concentrations were also observed in developing and aging male rats. Different control mechanisms appear to operate in mouse and man.

Aging↗

Evidence that the dopaminergic incerto-hypothalamic tract has a stimulatory effect on ovulation and gonadotrophin release.

2 micrograms dopamine (DA) were injected into particular hypothalamic sites containing dopaminergic nerve terminals, on the morning of pro-oestrus in cyclic rats, in which ovulation was blocked by administration of 35 mg/kg pento-barbitone Na, in the afternoon of pro-oestrus. DA in a specific area of the zona incerta (ZI) (medial area at A 5.4 mm; de Groot atlas), and medial anterior hypothalamus (AH) overcame the pentobarbitone block and induced ovulation. Injections into the median eminence and preoptic area were ineffective, as were injections of 5-hydroxytryptamine and nor-adrenaline into the ZI. Injection of 2 micrograms haloperidol and lesions in the ZI inhibited ovulation in otherwise untreated cyclic rats. Lesions induced constant dioestrus for 14 +/- 0.7 days, but the animals were not pseudopregnant. 2 micrograms DA were also injected into the ZI of ovariectomised rats primed with 2 micrograms oestradiol benzoate 48 h before; this treatment stimulated a rise in plasma LH approximately 40 min later. These findings indicate that the dopaminergic incerto-hypothalamic tract which has nerve terminals in the ZI and AH has a stimulatory role in the control of gonadotrophin release.

Animals↗

Studies on the control of gonadotrophin release in the gonadectomized male rat: evidence for a lack of involvement of the hypothalamic noradrenergic system in the long-term castrated rat.

The effects of castration with or without testosterone replacement in the adult male rat were studied to investigate possible hypothalamic mechanisms by which changes in gonadotrophin secretion occur at different times after castration, with particular reference to the continuing LH rise and its lack of suppression by testosterone in the long-term castrated rat. Castrated rats received either subcutaneous silicone elastomer implants containing testosterone or empty implants at the time of castration, and a sham-operated group served as controls. At 1, 10 and 40 days after castration, there were six-, 15- and 25-fold rises respectively in LH and 1.5-, two- and fivefold rises in FSH. However, there were no significant changes in hypothalamic noradrenaline concentration and turnover or in alpha-adrenoceptor density and affinity at any time after castration. Testosterone implants were effective in suppressing gonadotrophin release at 1 and 10 days, but not at 40 days after castration, and did not significantly affect hypothalamic noradrenaline turnover or alpha-adrenoceptors at any time. Neither acute inhibition of the noradrenergic system, using either the alpha-adrenoceptor blockers phenoxybenzamine and phentolamine or the synthesis inhibitor alpha-methyl-p-tyrosine, nor chronic depletion of hypothalamic noradrenaline by 6-hydroxydopamine had any significant effect on the normal rise in LH levels seen on days 10 and 40 after castration, and did not alter the ability of testosterone to suppress LH levels. This indicates that, in the long-term castrated rat, the noradrenergic system may not be involved in the control of gonadotrophin release. However, at 16 h after castration, alpha-adrenoceptor blockers and alpha-methyl-p-tyrosine did reduce LH levels, indicating that the noradrenergic system is likely to be involved in the short-term response to castration.

Adrenergic alpha-Antagonists↗

Sexual differentiation of rat liver carbonic anhydrase III.

Using radioimmunoassay, the concentration of carbonic anhydrase III in the livers of adult male rats was found to be approx. 30-times greater than that observed in mature females. Castration of male rats led to a marked reduction in liver carbonic anhydrase III concentrations which could be partially restored to control levels by testosterone replacement. Administration of testosterone to ovariectomised female rats induced about a 5-fold increase in liver carbonic anhydrase III concentration. Immunoprecipitation analysis of the products of liver mRNA translation in vitro with antiserum specific for carbonic anhydrase III showed that hormonal control of the levels of carbonic anhydrase III in liver is mediated by changes in the amount of translatable carbonic anhydrase III mRNA. Marked changes in liver carbonic anhydrase III concentrations were also observed in developing and ageing male rats.

Age Factors↗

Androgen-linked control of rat liver carbonic anhydrase III.

The concentration of carbonic anhydrase III (CAIII) in male rat liver was found to be 30 times greater than that in the female. Castration of male rats led to marked reduction in liver CAIII concentrations which could be partially restored to control levels by testosterone replacement. Marked developmental and senescence changes in liver CAIII were also observed in male rats.

Aging↗

Melanocyte stimulating hormone and the inhibition of sexual behaviour in the female rat.

When administered to ovariectomized females, primed with oestradiol benzoate (OB) and progesterone, alpha-MSH increased lordosis behaviour in those rats that showed a low level of receptivity but in rats that were receptive it had an inhibitory effect. alpha-Melanocyte stimulating hormone also inhibited proceptive behaviour in these females. Luteinizing hormone releasing hormone (LHRH), on the other hand, failed to have a similar inhibiting effect although it did stimulate lordosis. While adrenalectomy failed to alter the stimulatory effect of alpha-MSH on lordosis it completely prevented the inhibitory actions of alpha-MSH on both lordosis and proceptive behaviour. Thus, while alpha-MSH may stimulate lordosis through a central action its inhibitory effects on lordosis and proceptive behaviour are probably mediated via the adrenal glands. Although alpha-MSH may stimulate the secretion of an adrenal steroid that blocks the facilitatory action of progesterone on female sexual behaviour the present results suggest that this inhibitory effect could be mediated by a catecholamine.

Adrenal Cortex Hormones↗

Penile ice pack.

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Cryotherapy↗

Indoleamine and catecholamine concentrations in the mid-term human fetal brain.

Because of the likelihood that androgen-induced sex specific brain differentiation is mediated by various neurotransmitters, their concentrations were measured in the mid-term human fetal hypothalamus, cortex and cerebrospinal fluid (CSF). Tissue was collected from 32 hysterotomy specimens aged from 10 to 23 weeks, immediately frozen in liquid nitrogen, and stored at -20 degrees C. 5-Hydroxytryptamine (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) levels were measured by a fluorometric assay. Cord serum testosterone levels were measured by radioimmunoassay. In the male fetuses, hypothalamic concentrations of 5-HT, 5-HIAA and NE were all significantly increased in comparison to those in the cortex. Because the number of female fetuses was small, only the 5-HIAA levels were seen to be significantly higher in the hypothalamus than in the cortex. In the CSF from fetuses of both sexes, the DA levels were greatly raised. Concentrations of NE were significantly higher in male fetuses aged from 14-16 weeks, a time when plasma testosterone levels are also elevated. It is hypothesized that the raised plasma testosterone and hypothalamic NE concentrations are inter-related.

Brain↗

Plasma amine and hormone changes in 'post-partum blues'.

The relationship between hormone levels, plasma catecholamines, and mood disturbances has been investigated in 44 patients during days 2 to 5 of the immediate post-partum period. Fifty-two per cent of the mothers showed periods of emotional lability although there was no significant correlation between plasma concentrations of FSH, prolactin, oestrone, oestradiol, cortisol, or progesterone and the incidence of post-partum blues. In contrast there was a significant reduction of circulating catecholamines which correlated with mood disturbances. Women who experienced only a single day of post-partum blues had significantly lower levels of noradrenaline and adrenaline on that day compared with preceding or subsequent days.

Adult↗

Physical changes associated with the onset of precocious puberty in rats after treatment with PMSG.

Body dimensions, composition, oxygen consumption and core temperature were measured in 2 groups of immature rats treated with PMSG. The first group weighed over 60 g on Day 27 of life and responded to PMSG treatment by ovulating; the second group weighed less than 60 g and did not ovulate after PMSG. Body composition, expressed as a percentage of body weight, was identical in the two groups, but growth rate, oxygen consumption and body temperature were all lower in the lighter animals. Oxygen consumption and body temperature were manipulated by altering temperature (i.e. 5, 22 and 30 degrees C) or by hyperphagia, and a positive correlation was found between body temperature and the occurrence of ovulation.

Animals↗

Hormonal changes in the immature rat after administration of pregnant mare serum gonadotrophin: influence of body weight.

We have shown previously that pregnant mare serum gonadotrophin (PMSG) induces ovulation only in rats weighing over 60 g on the day of injection. The under-60 g rats do not ovulate although they secrete a preovulatory surge of a pleiomorphic form of LH. Presumably this pleiomorph is inactive. Comparisons were made of plasma hormone concentrations in rats treated with PMSG that weighed over and under 60 g. The measurements were made on samples taken between 13.00 and 22.00 h on the day of the expected preovulatory LH surge. Prolactin and corticosterone levels were lower in the lighter group compared with the heavier group. A midday pulse of GH detected in the over-60 g animals did not occur in the under-60 g group. Levels of ACTH were slightly higher in the under-60 g rats and together with the low corticosterone concentrations indicate adrenal insensitivity. Oestradiol, progesterone and TSH concentrations were the same in the two groups. Since progesterone secretion is under LH control, the 'inactive' pleiomorphic form of LH must have steroidogenic activity. There was an indication that the under-60 g rats also secreted a pleiomorphic form of FSH. Reports in the literature indicate that prolactin, corticosterone and GH have a positive modulatory influence on natural puberty. They may also influence precocious puberty induced by PMSG, since in the unresponsive under-60 g rat plasma levels of these three hormones were low. Perhaps the release of one or more of these hormones is dependent upon the physical maturity of the animal as represented by body weight.

Adrenocorticotropic Hormone↗

Preparation of the cellulase from the cellulolytic anaerobic rumen bacterium Ruminococcus albus and its release from the bacterial cell wall.

1. Most of the cellulase (CM-cellulase) elaborated by the rumen bacterium Ruminococcus albus strain SY3, which was isolated from a sheep, was cell-wall-bound. 2. The enzyme could be released readily by washing either with phosphate buffer or with water. 3. The amount of enzyme released was affected by the pH and ionic strength of the phosphate buffer. 4. The cell-wall-bound enzyme was of very high molecular weight (>>1.5x10(6)) as judged by its chromatographic behaviour on Sephacryl S-300. 5. The molecular weight of the extracellular enzyme was variable and depended on the culture conditions. 6. When cellobiose was used as the energy source and the medium contained rumen fluid (30%), the extracellular enzyme was, in the main, of high molecular weight. 7. When cellulose replaced the cellobiose, the cell-free culture filtrate contained only low-molecular-weight enzyme (M(r) approx. 30000) in late-stationary-phase cultures (7 days). 8. Cultures that did not contain rumen fluid contained mainly low-molecular-weight enzyme. 9. Under some conditions the high-molecular-weight enzyme could be broken down to some extent into low-molecular-weight enzyme by treatment with dissociating agents. 10. Cell-free and cell-wall-bound enzymes showed the same relationship when the change in fluidity effected by them on a solution of CM-cellulose was plotted against the corresponding increase in reducing sugars, suggesting that the enzymes were the same. 11. It is possible that R. albus cellulase exists as an aggregate of low-molecular-weight cellulase components on the bacterial cell wall and in solution under certain conditions.

Carboxymethylcellulose Sodium↗