Search PubMedSearch

Biomedical subjects

A M Hughes

Publications and source records attributed to A M Hughes.

At least 19 recordsLinked to original sources

Enterohepatic distribution of carnitine in developing piglets: relation to glucagon and insulin.

L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p = 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p = 0.0006), insulin (p = 0.0001), and glucagon:insulin ratio (p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns.

Aging

Comparative effects of preoptic area infusions of opioid peptides, lesions and castration on sexual behaviour in male rats: studies of instrumental behaviour, conditioned place preference and partner preference.

The effects on the sexual behaviour of male rats of excitotoxic amino acid-induced lesions of the medial preoptic area-anterior hypothalamic area (mPOA/AHA), infusions of beta-endorphin, alpha-melanocyte stimulating hormone and naloxone into the mPOA/AHA, systemic naloxone and castration were compared using different behavioural paradigms. These included measures of unconditioned copulatory behaviour, instrumental responses for an oestrous female presented under a second-order schedule of reinforcement, conditioned place preference and partner preference. The results demonstrate that manipulations of the mPOA/AHA markedly affect consummatory aspects of sexual behaviour (mounting, intromitting and ejaculating) but tend not to affect appetitive or reward-related aspects of sexual behaviour, although intra-mPOA/AHA alpha MSH did result in a small increase in instrumental responses, while beta-endorphin infused into the mPOA/AHA also abolished preference for an oestrous over an anoestrous female. Systemic naloxone, on the other hand, reduced instrumental behaviour and a place preference conditioned by prior sexual interaction, while the same compound infused into the mPOA/AHA markedly facilitated copulatory responses but did not affect other measures of appetitive sexual responses. Castration caused an extremely rapid attenuation of conditioned place preference which was apparent before the males had experienced reductions in their copulatory performance. This treatment only slowly reduced partner preference. The results indicate that the use of several behavioural procedures can reveal discrete actions of neuroendocrine treatments on separable psychological processes which underly the integrated pattern of masculine sexual behaviour. In particular, they suggest that the mPOA/AHA is especially concerned with the copulatory responses of mounting and intromitting, but is much less important for a variety of appetitive sexual acts as well as sexual reward, as measured in the place preference procedure. The marked effects of castration on conditioned place preference taken together with the lack of effect of lesions of the mPOA/AHA on this measure indicate that testosterone affects sexual reward-related processes by an action at a site other than the mPOA/AHA. The implications of these findings are discussed.

Animals

Cancerization of eccrine sweat ducts in Bowen's disease as studied by light microscopy, DNA spectrophotometry and immunohistochemistry.

This study assesses the incidence, histogenesis, and significance of eccrine sweat duct involvement in Bowen's disease (BD). In a review of 96 cases of BD, four showed eccrine duct involvement on hematoxylin and eosin-stained histologic sections. One case was analyzed for deoxyribonucleic acid (DNA) ploidy by using computerized image analysis on Feulgen-stained slides. Sections were also stained immunohistochemically, using antibodies to carcinoembryonic antigen (CEA), gross cystic disease fluid protein (GCDFP), and S-100 protein, and for cytokeratins (CAM 5.2, AE 1/3). Our results showed that, in BD, (a) the eccrine sweat ducts can be extensively involved by atypical cells, (b) the atypical eccrine duct cells had an aneuploid DNA pattern, and (c) the atypical eccrine duct cells were negative for CEA, GCDFP, and S-100 protein but were positive for cytokeratins. We conclude that (a) the frequency of eccrine duct involvement in BD is relatively low (approximately 4 to 9%), (b) the aneuploid DNA pattern makes a benign squamous metaplasia unlikely, (c) the immunohistochemical results exclude coincidental Paget's disease or carcinoma of eccrine sweat glands, (d) the involvement of eccrine sweat ducts may represent a direct extension of the neoplastic epidermal keratinocytes, and (e) this process may have practical implications in the recurrence of superficially treated cases of BD.

Bowen's Disease

Psychiatric disorders in a dental clinic.

This paper describes the psychiatric disorders seen in 138 consecutive attenders at a psychiatric clinic in a dental hospital. The disorders were rated using a standardised interview, and assigned a diagnosis in accordance with a multiaxial classification known as the DSM-III. The rate of psychiatric disorder seen in these patients was over 90% and the implications of this are discussed.

Depressive Disorder

Essential hypertension: the relationship of psychological factors to the severity of hypertension.

165 hypertensive patients attending one general practice in Portugal were found to report significantly higher scores on measures of neuroticism, anxiety, depression and general psychological distress than 152 normotensive patients at the same practice. Hypertensive patients with evidence of organ damage exhibited significantly higher depression scores than those without such damage. These differences between normotensives and hypertensives, and between hypertensive with and without organ damage are discussed and previous research in this area is reviewed.

Adult

The effects of simultaneous or separate infusions of some pro-opiomelanocortin-derived peptides (beta-endorphin, melanocyte stimulating hormone, and corticotrophin-like intermediate polypeptide) and their acetylated derivatives upon sexual and ingestive behaviour of male rats.

Intraneuronal post-translational cleavage of pro-opiomelanocortin yields a variety of peptides including beta-endorphin, melanocyte stimulating hormone and corticotrophin-like intermediate polypeptide, some of which are subsequently N-acetylated. Such peptides may be co-released from neuronal terminals, and so these experiments explored the effects of co-administration of some of them on sexual behaviour in the male rat, which is known to be sensitive to hypothalamic infusions of beta-endorphin. Peptides were infused into the pre-optic-anterior hypothalamic area bilaterally in doses up to 320 pmol, and males allowed access to a sexually receptive female and/or a sweet solution (0.1% Acesulfame-K) for 15 min, so that both sexual and ingestive behaviour could be studied. beta-Endorphin(1-31) by itself inhibited sexual interaction, confirming our previous data. Acesulfame-K ingestion was inhibited in control-infused rats in the presence of a female, but this inhibition was released when sexual behaviour was itself diminished by beta-endorphin(1-31). Both the acetylated and non-acetylated forms of melanocyte stimulating hormone (alpha-melanocyte stimulating hormone and des-acetyl melanocyte stimulating hormone) stimulate sexual behaviour; latencies both to ejaculation and to resumption of copulatory behaviour after an ejaculation (post-ejaculatory interval) were reduced. However, infusion of either corticotrophin-like intermediate peptide or N-acetylated beta-endorphin (1-31) had no effect on either sexual or ingestive behaviour. Infusion of either acetylated melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone mixed with beta-endorphin(1-31) prevented the inhibitory effect of the latter on sexual behaviour. Dose-response studies showed that the behavioural effect of such mixtures depended upon the molar ratios of the two peptides, rather than their absolute concentrations. The higher the ratio in favour of alpha-melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone, the greater the display of sexual behaviour. Infusing either corticotrophin-like intermediate polypeptides or N-acetyl beta-endorphin(1-31) with beta-endorphin(1-31) did not prevent the inhibition of sexual activity expected with beta-endorphin(1-31) alone. These results are discussed in terms of the functional consequences of co-release of proopiomelanocortin peptides from hypothalamic nerve terminals.

Acetylation

Synaesthesia and major affective disorder.

Two patients with major affective disorder are described. In both cases synaesthesia was a prominent and integral feature of the disorder. The discussion considers the relationship of perceptual upset and affective disorders.

Adult

Oxytocin in the central nervous system and sexual behaviour in male rats.

Concentrations of oxytocin (OT) and vasopressin (AVP) were measured in cerebrospinal fluid (CSF) obtained from the cisterna magna of freely moving rats. Basal levels of OT and AVP were approximately 9 fmol/ml in both male and female. In the male rats this increased to approximately 18 fmol/ml 5 min after ejaculation, and 27 fmol/ml 20 min after ejaculation. No increase from basal levels occurred when males were placed with unreceptive females, or alone in the test environment. AVP levels were unchanged in any condition. Preliminary investigations indicate that discrete electrolytic lesions to the lateral and posterior parvocellular hypothalamic paraventricular nucleus (PVN) abolished this ejaculation-associated increase in CSF OT, prolonged mount and intromission latencies and reduced the absolute postejaculatory interval (PEI). We conclude that intracerebrally projecting OT systems may be activated during coitus and may contribute to the mechanisms underlying postejaculatory refractoriness.

Animals

Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats.

beta-Endorphin was infused bilaterally into the medial preoptic area-anterior hypothalamic continuum at doses of 5, 10 and 40 pmol each side. The highest dose selectively abolished mounting, intromitting and ejaculating in sexually experienced male rats paired with an oestrous female. Males infused with 40 pmol beta-endorphin still followed the female, investigated her anogenital region and other parts of her body, but made abortive attempts to mount. A dose of 5 pmol beta-endorphin had no effect, but 10 pmol proved partially effective. The same males, in other tests, were allowed to ingest a highly preferred, sweet, non-calorific solution (acesulfame-K) in the absence of a female. beta-Endorphin infusions (up to 40 pmol) into the same area of the hypothalamus had no effect on this behaviour. Control males allowed simultaneous access both to an oestrous female and to the sweet solution copulated normally but reduced their ingestive behaviour, despite there being sufficient time during tests for both to occur. beta-Endorphin (40 pmol) infused into the preoptic area-anterior hypothalamic continuum under these conditions suppressed sexual interaction, but ingestion of acesulfame-K increased to values observed when the female was absent. beta-Endorphin infused into neighbouring areas of the brain had different behavioural effects. Sexual behaviour was not inhibited, and ingestion of acesulfame-K was unaltered, when beta-endorphin was infused either into the bed nucleus of the stria terminalis or the rostral ventromedial hypothalamus. However, infusions of cholecystokinin-8 into the ventromedial hypothalamus suppressed acesulfame-K ingestion in most animals, showing that the cannulae were placed in an area regulating ingestive behaviour. The inhibition of sexual behaviour after preoptic area-anterior hypothalamic continuum infusions of beta-endorphin was prevented by either pretreating rats with 1 mg/kg naloxone intraperitoneally, or by infusing a putative delta opiate receptor blocker (0.5 pmols ICI 174864) into the preoptic area-anterior hypothalamic continuum 5 min prior to beta-endorphin treatment. ICI 174864 administered alone significantly increased mount rate and reduced the post-ejaculatory refractory period in copulating males. These experiments suggest that there is both neurochemical and neuroanatomical specificity relating beta-endorphin to sexual behaviour in the male rat.

Animals

Psychogenic pain: a study of marital adjustment.

The marital adjustment of patients with psychogenic pain disorder was evaluated and compared with a matched group of patients with other neurotic disorders. Pain patients spouses were found to have better marital adjustment and less psychiatric morbidity than the spouses of neurotic patients. These findings are discussed in terms of the concepts of "sick role homeostasis" and "tertiary gain".

Adaptation, Psychological

Psychological aspects of chronic pain.

This paper summarizes psychological factors which can influence a patient's experience of chronic pain--namely personality and social variables, mood disturbance, hysteria and others. Psychological treatments which are available for pain management, including behavioural-cognitive therapies and relaxation, and the functions of multidisciplinary pain units are described.

Chronic Disease

Cytocidal effect of rifamycin derivatives on ascites tumor cells: studies with [125I]iododeoxyuridine.

The cytotoxicity of 2 rifamycin derivatives, rifazone-82 and rifampicin, on mouse ascites cells was studied, using the [125I]iododeoxyuridine (IUDR) method of labeling the tumor cells. This technique allows a distinction to be made between a cytocidal and cytostatic effect. The 2 drugs exerted a cytocidal effect against 2 non-leukemic cell lines, but had no effect against 3 leukemic lines.

Adenocarcinoma

Inhibition of adenocarcinoma TA3 ascites tumor growth by rifamycin derivatives.

A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF1/J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)1, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-82 (R-82). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and R-82. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

Adenocarcinoma