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Biomedical subjects

J S Jenkins

Publications and source records attributed to J S Jenkins.

At least 73 records · Page 4Linked to original sources
PubMed1988

The combined use of sodium valproate and metyrapone in the treatment of Cushing's syndrome.

We have investigated the combined use of metyrapone and sodium valproate in the treatment of five cases of dexamethasone-suppressible Cushing's disease and one case with dexamethasone non-suppressible disease. Metyrapone alone reduced 24 h urinary free cortisol (UFC) and plasma cortisol concentrations. Addition of sodium valproate to metyrapone produced a further reduction in these values in five of six patients with a reduction in plasma ACTH in three of five patients who had dexamethasone-suppressible disease. Plasma 11-deoxycortisol increased markedly on metyrapone. However, addition of valproate produced a further rise in 11-deoxycortisol values in four of five patients including the patient with dexamethasone non-suppressible disease. The results suggest that valproate may be a useful addition to metyrapone in the medical treatment of some patients with Cushing's syndrome and that it may have an action both at the hypothalamus and peripherally.

Adrenocorticotropic Hormone↗
PubMed1988

Vasoactive intestinal peptide and anterior pituitary function.

Vasoactive intestinal peptide (VIP) is a highly basic 28 amino-acid peptide which was first isolated from porcine small intestine (Said & Mutt, 1970). It is related to several other peptides including PHI (peptide with N-terminal histidine and C-terminal isoleucine amide), secretin, glucagon, and has some sequences similar to those of growth hormone releasing hormone (Fig. 1). The amino-acid sequence of human VIP is identical with that of the porcine form (Itoh et al., 1983). It has been shown that human VIP is cosynthesized with PHM (peptide with N-terminal histidine and C-terminal methionine amide, the human analogue of PHI) from the same large precursor protein (Itoh et al., 1983).

Amino Acid Sequence↗
PubMed1988

Vasoactive intestinal peptide and the stimulation of lactotroph growth by oestradiol in rats.

Treatment with a high dose of oestradiol for 6 months caused hyperprolactinaemia and pituitary hyperplasia in female Wistar-Furth rats. Changes in the vasoactive intestinal peptide (VIP) and dopamine content of the hypothalamus and pituitary were also found. The hypothalamic dopamine concentration was only slightly reduced and, although the concentration of dopamine in the pituitary was less in treated animals, the total pituitary content was increased. The concentration of VIP in the pituitary was increased by oestradiol treatment but decreased in the non-median eminence hypothalamus. In the median eminence the VIP content was increased by oestradiol treatment and the amount present correlated positively and significantly with pituitary wet weight in animals treated with both oestradiol and fluphenazine. In Fischer 344 rats, oestradiol produced greater incremental changes in pituitary wet weight and plasma concentrations of prolactin than in Wistar controls and the increase in the pituitary concentration of VIP was five times greater. Although peptide turnover has not been measured, these results suggest that oestradiol, as well as having a direct action, stimulates pituitary lactotrophs by increasing pituitary concentrations of VIP.

Animals↗
PubMed1987

Hyperprolactinemia reduces vasoactive intestinal peptide in the anterior pituitary glands of rats.

The concentration of vasoactive intestinal polypeptide (VIP) in the anterior pituitary gland of female rats was significantly reduced by pituitary implants, prolactin-secreting tumours or dopamine blockade-induced hyperprolactinemia. Oestradiol implants increased plasma prolactin (PRL) to 12 times and increased pituitary VIP to 3.5 times that of controls after one week. The dopamine agonist bromocriptine significantly reduced pituitary VIP at doses within the clinically used range. These results provide evidence for a suppressive effect of plasma PRL on pituitary VIP, which may be effected by a dopaminergic mechanism, but is over-ridden by oestrogen.

Animals↗
PubMed1987

Immunohistochemical localization of oxytocin and vasopressin in the adrenal glands of rat, cow, hamster and guinea pig.

The distribution of oxytocin and vasopressin in the adrenals of rat, cow, hamster and guinea pig has been studied by use of immunohistochemical techniques. In all the species studied the adrenal cortex contained both peptides; the staining in the zona glomerulosa being more intense than that in zona fasciculata or zona reticularis. The medulla, however, showed considerable species variation. In the cow, both peptides appear to be present in the adrenergic and noradrenergic cells, though staining was particularly prominent in cortical islands interspersed within the medullary tissue. In the rat, groups of medullary cells positive for both peptides were found, though it was not possible to associate these groups with particular chromaffin cell types. In the hamster oxytocin was present only in adrenaline-containing cells, whereas vasopressin was present in all medullary cells. The guinea pig medulla, which contains only adrenaline-secreting cells, was positive for both peptides. The possibilities that vasopressin and oxytocin have an autocrine or paracrine role in functioning of the adrenal gland is discussed.

Adrenal Cortex↗
PubMed1987

Endogenous vasopressin affects postural control of blood pressure in man.

1. Six healthy volunteers received intravenous infusions of isotonic (0.9% NaCl) and hypertonic (3% NaCl) saline on separate days. There were no significant changes in blood pressure or forearm blood flow, despite an increase in plasma arginine vasopressin (AVP) during hypertonic saline. 2. Immediately and 10 min after passive tilting to 50 degrees, mean forearm blood flow fell by 17.1 and 14.3% compared with the values in the supine position during isotonic saline and by 40.3 and 43.3% during hypertonic saline. Forearm vascular resistance rose by 23.6 and 17.8% with isotonic saline and by 80.2 and 88.2% with hypertonic saline for the two readings in the tilted compared with the supine position. 3. Tilting was associated with a 14.9 and 12.1% rise in diastolic blood pressure immediately and 10 min after assuming this position during hypertonic saline, and a rise of 6.4% in mean arterial pressure. 4. The results from this study are similar to those obtained previously, when small amounts of AVP were infused. They provide further evidence that AVP may have a physiological role in the postural regulation of blood pressure.

Adult↗
PubMed1987

C3 degradation products (C3d) in normal pregnancy.

Plasma C3 degradation products (C3d) were measured in 65 normal pregnancies and compared with those of non-pregnant women. No significant difference was detected between the two groups, although a difference had been previously reported. Plasma C3d estimations give an indication of complement activation and may be used as an indicator of disease activity in patients with systemic lupus erythematosus (SLE), irrespective of pregnancy.

Complement C3↗
PubMed1987

Increased creatine kinase activity in pituitary tumours of rat and man.

The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.

Adenoma↗
PubMed1987

Vasoactive intestinal polypeptide and dopamine in the hypothalamus and pituitary of ageing rats with prolactinomas.

Vasoactive intestinal peptide (VIP), an dopamine have been measured in the hypothalamus and anterior pituitaries of female rats at three different ages. Rats aged 19 months had a high incidence (35%) of prolactin-secreting tumours of the pituitary and these animals had increased hypothalamic and pituitary VIP compared with three-month-old rats or rats without tumours. VIP in old animals without tumours was similar to that in young animals. The third group, with an even more advanced age of 22-28 months, had a lower incidence of PRL-secreting tumours, and pituitary and hypothalamic VIP concentrations similar to those in young animals. Dopamine was significantly increased in the pituitaries of 22-28-month-old nontumorous rats and slightly raised in 19-month-old rats. We conclude that the increased pituitary and hypothalamic VIP content of 19-month-old rats could be a factor in the development of tumours seen at this age, and the differences seen in the two groups of old rats may be related to changes in the steroid environment.

Age Factors↗
PubMed1987

Vasoactive intestinal peptide increases intracellular free calcium in rat and human pituitary tumour cells in vitro.

Prolactin secretion by a human pituitary tumour cell line produced in our laboratory was stimulated by TRH, vasoactive intestinal peptide (VIP) and epithelial growth factor (EGF). All raised the intracellular concentration of free calcium (Ca2+ i) of cells loaded with a fluorescent quinoline Ca2+ indicator in suspension, but the effect of TRH was much more rapid and less prolonged than that of VIP and EGF. Both TRH and VIP also increased Ca2+ i in GH3 rat pituitary tumour cells, but in this cell line the effect of VIP was only found in attached cells grown on cover-slips. In both human and rat cell lines, the increase in Ca2+ i produced by TRH was independent of extracellular calcium, whereas this was a requirement for the action of VIP and EGF. It is concluded that the prolactin secretagogues, VIP and probably EGF, increase Ca2+ i through an effect on plasma membrane calcium channels and that this effect differs from that of TRH.

Animals↗
PubMed1987

Arginine vasopressin and oxytocin in the bovine adrenal gland.

The concentrations of immunoreactive oxytocin and arginine vasopressin (AVP) and their respective neurophysins (NpI and NpII) were compared in bovine adrenal cortex and medulla. While the concentration of AVP was similar in both tissues there was more NpII in the medulla. The medulla also contained much more oxytocin and NpI than the cortex. The extracted AVP and oxytocin had identical retention times to those of the synthetic peptides on high-performance liquid chromatography (HPLC) and were biologically active in assays for antidiuretic and milk-ejection activity (with potencies of 310 units/mg and 340 units/mg respectively). Adrenal NpI and NpII behaved identically to commercially available neurohypophysial proteins on HPLC. Oxytocin, NpI and AVP were assayed in five subcellular fractions of bovine adrenal medulla prepared on discontinuous sucrose gradients. A high proportion of each co-localized with noradrenaline and adrenaline in the chromaffin granule fraction. Binding of [3H]AVP and [3H]oxytocin to crude bovine adrenal medulla membranes was dependent upon both time and temperature. The binding sites were specific and saturable: studies with the V1 AVP antagonist d(CH2)5Tyr(Me)AVP and the V2 agonist 1-deamino-8-D-AVP indicated that the AVP receptor was V1 in specificity. Scatchard plots showed that each ligand interacted with a single high-affinity, low-capacity binding site: oxytocin dissociation constant (Kd) 3.1 +/- 0.29 nmol/l, maximum binding capacity (Bmax) 89.6 +/- 18.4 fmol/mg protein (n = 3); AVP Kd 0.73 +/- 0.02 nmol/l, Bmax 26.5 +/- 8.3 fmol/mg protein (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1986

Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor.

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.

Adult↗
PubMed1986

Haemodynamic effects of vasopressin in man are related to posture.

Ten healthy volunteers received intravenous infusions of arginine vasopressin (AVP) at 0.1 m-unit min-1 kg-1 and 5% D-glucose on separate days. AVP caused a small fall in forearm blood flow and small rises in mean arterial pressure and systemic vascular resistance. Cardiac output was unaffected. When subjects were tilted to 50 degrees the fall in forearm blood flow was much greater, mean fall being 44.8% with AVP compared with 18.2% with D-glucose. Cardiac output also fell significantly more with AVP, and diastolic pressure, mean arterial pressure and systemic vascular resistance rose significantly more on tilting during AVP infusion than with D-glucose. Six of the same volunteers were given sequential infusions of 'low dose' (0.0125 m-unit min-1 kg-1) and 'high dose' (0.3 m-unit min-1 kg-1) AVP on a third occasion. Tilting still produced a mean fall in forearm blood flow of 41.2% during low dose infusion, despite a mean plasma AVP level of only 1.9 pg/ml, which is well within the physiological range. When the AVP concentration was increased 24-fold to the high dose, forearm blood flow fell only a further 8.8%. The low dose infusion was also associated with a marked fall in cardiac output on tilting and a rise in systemic vascular resistance. We conclude that AVP has profound haemodynamic effects in man at physiological concentrations. Although these effects are modest in the supine position, they become marked on tilting, suggesting a possible role for AVP in the postural control of blood pressure.

Adult↗
PubMed1986

Human platelet arginine vasopressin.

Approximately 90% of arginine vasopressin circulating in blood is associated with the platelets. Studies in six patients with cranial diabetes insipidus indicate that the platelet vasopressin originates in the hypothalamus and is taken up from plasma. Extracted platelet vasopressin is chromatographically identical to the posterior pituitary peptide and biologically active. Infusion of low-doses of exogenous vasopressin into 10 normal male subjects caused a marked rise in both plasma and platelet hormone concentrations. Stimulation of endogenous vasopressin release by hypertonic saline (0.51 mol/l) infusion for 135 min in five male subjects also caused a rise in platelet and plasma peptide concentrations. In seven male smokers, the deep inhalation of two consecutively smoked unfiltered cigarettes caused a significant rise in both platelet and plasma vasopressin. Baseline platelet vasopressin concentrations in the smokers were higher than in the non-smoking males even after 10 hours abstinence.

Adult↗
PubMed1986

Responses of neurohypophysial peptides to hypertonic saline and insulin-induced hypoglycaemia in man.

In order to investigate the possible role of oxytocin in osmoregulation and its response to stress, plasma immunoreactive oxytocin was measured during hypertonic saline infusion and insulin-induced hypoglycaemia in a group of normal subjects, four patients with idiopathic diabetes insipidus and one patient with DIDMOAD syndrome (the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness). The results were compared with those of plasma immunoreactive vasopressin to the same stimuli. As expected, there was a rise in plasma vasopressin in the normal subjects to both tests: this was absent in the patients with diabetes insipidus. Plasma oxytocin did not rise during hypertonic saline infusion in either group of subjects. The response of oxytocin to insulin-induced hypoglycaemia (0.15 U/kg soluble insulin) in normal subjects was much more variable. One highly symptomatic volunteer showed a marked rise in oxytocin. Two subjects also showed a rise when retested with 0.19 U/kg soluble insulin. There was no response of oxytocin to a standard-dose insulin test in the patients with diabetes insipidus. The data suggest that, in man, oxytocin is not involved in osmoregulation but that it may be secreted in response to marked hypoglycaemia.

Adult↗
PubMed1986

Chronic hypernatraemia and hypothermia following subarachnoid haemorrhage.

We describe a 30 year old man who developed chronic adipsic hypernatraemia and hypothermia following a subarachnoid haemorrhage from an anterior communicating artery aneurysm. Anterior pituitary function tests were normal. Hypothermia was demonstrated over 4 years with loss of the ability to control heat conservation despite body temperatures as low as 30 degrees C. He failed to experience thirst despite plasma sodium concentrations of up to 187 nmol/l and plasma osmolalities of up to 397 mOsm/kg. The slope of the plasma vasopressin-plasma osmolality curve indicated loss of the osmoreceptor. There was an absent vasopressin response to insulin-induced hypoglycaemia but a normal response to apomorphine. The apomorphine-stimulated immunoreactive vasopressin was shown to behave identically to the synthetic peptide on HPLC and was bioactive.

Adult↗