Fade In, Fade Out: Do Shifts in Visual Perspective Predict the Consistency of Real-World Memories?

Memories of our personal past are not exact accounts of what occurred. Instead, memory reconstructs the past in adaptive-though not always faithful-ways. Using a naturalistic design, we asked how the visual perspective adopted in the mind's eye when recalling the past-namely, an "own eyes" versus "observer" perspective-relates to the stability of autobiographical memories. We hypothesized that changes in visual perspective over time would predict poorer consistency of memories. Young adults (N = 178) rated the phenomenology of and freely recalled self-selected memories of everyday events at two time points (10 weeks apart). Multilevel linear modeling revealed, as expected, that greater shifts in visual perspective over time predicted lower memory consistency, particularly for emotional details. Our results offer insight into the factors that predict the fidelity of memories for everyday events. Moreover, our results may elucidate new metrics that are useful in interpreting eyewitness testimony or experiences relayed in clinical contexts.

Fibrin tissue adhesive versus nasal packing in endoscopic nasal surgery: a systematic review and meta-analysis.

BACKGROUND: It has been proposed that fibrin tissue adhesive (FTA) can act as an effective alternative to nasal packing in managing the postoperative symptoms of endoscopic nasal surgery. METHODOLOGY: MEDLINE, Embase, Cochrane Library, The Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov were searched for randomised controlled trials comparing FTA with nasal packing in endoscopic nasal surgery. The primary outcome of interest was bleeding; secondary outcomes included pain, nasal obstruction, infection, adhesions and the formation of granulation tissue. All trials underwent a risk of bias assessment, and a meta-analysis was performed using a random effects model. RESULTS: 315 studies were found, of which four were eligible for inclusion (n = 152). Bleeding was reported in all, with the meta-analysis favouring the packing group, although this was not significant. Nasal obstruction and granulation severity were significantly lower in the FTA group, however, no difference was noted for the outcomes of pain, infection or adhesions. CONCLUSION: Our results indicate minor advantages for using FTA over nasal packing. Unfortunately, the included studies show significant heterogeneity and risk of bias. Based on the available evidence, clinicians must balance the higher cost of FTA against the limited advantages for the patient.

The surface concentration of H-2 antigens on mouse pancreatic beta-cells and islet cell transplantation.

Measurement of the concentration of H-2 complex antigens in the surface membrane of mouse pancreatic beta-cells by a quantitative immunoferritin-labeling technique revealed that the antigens were present in very small amounts on the beta-cells of five strains. A comparison of the labeling densities in the five strains suggested that beta-cells from C57BL/10Sn congenic strains have about half the H-2 antigen density of BALB/c and C3H/HeJ cells. In C57BL/10Sn mice the antigen density on beta-cells was slightly greater than that on erythrocytes, about 20% of that on thymocytes, and about 2.5% of that present on peritoneal macrophages. Intraperitoneal allografts of c57BL/10Sn islets were uniformly rejected by B10.BR/SgSn diabetic recipients only when the islets were accompanied by 10(7) peritoneal lymphoid cells. When transplanted without peritoneal cells, C57BL/10Sn islets were only marginally rejectable. In a group of nine such allografts, three diabetic recipients were permanently cured and three others showed rejection times of about 30 days. Sensitization of the three mice showing permanent cures, using 10(7) allogeneic peritoneal cells at about 40 days after the transplant, did not cause rejection of the allografts. Isogeneic transplantation of cell suspensions from dissociated islets of Langerhans was markedly less effective in controlling diabetes than intact islets, and dissociation did not obviously improve the rate of allograft survival. However, 5/19 diabetic mice receiving allografts of dissociated islet cells showed long-term reversals of diabetes that were unaffected by administration of 10(7) peritoneal cells at about 100 days after the transplant. Recipient mice whose diabetes was reversed by islet allografts and unaffected by specific sensitization had pancreatic insulin concentrations characteristic of diabetic mice. Our reversals of diabetes with untreated islet allografts may be due to the cleanliness of islet preparations obtained with a modified isolation technique, and to the very low density of H-2 complex antigens on C57BL/10Sn beta-cells.

Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist.

OBJECTIVE: The vasoconstrictor effect of endothelins (ET) is mediated by endothelin A (ETA) and endothelin B (ETB) receptors. Furthermore, ETB receptor stimulation results in release of vasodilators. Hence, ETA receptor antagonists should attenuate ET-mediated vasoconstriction. The aim of the present study was to evaluate and compare the effects of BQ-123, an ETA receptor antagonist, and bosentan, an ETA and ETB receptor antagonist, on coronary vasomotor tone, left ventricular systolic function and ET-1 efflux in the presence or absence of myocardial ischaemia/reperfusion. METHODS: Isolated rat hearts were perfused using a Langendorff preparation. Global ischaemia was induced on average by 68 +/- 2% (+/- standard error of the mean) reduction of a baseline perfusion flow-rate 10 min after introduction of ET antagonists. Thirty minutes of ischaemia was followed by 30 min reperfusion. ET-1 efflux in coronary perfusate was measured by radioimmunoassay. RESULTS: In non-ischaemic hearts (n = 7), BQ-123 (10(-6) M) perfusion induced a progressive decrease in coronary flow-rate compared with control group. This flow reduction persisted after wash-out of BQ-123. In contrast, bosentan (10(-5) M, n = 7) induced no change in perfusion rate. In the absence of ET antagonists (n = 16), there was a 22 +/- 6% post-ischaemic increase in perfusion flow-rate. BQ-123 (n = 5) but not bosentan (n = 12) abolished this post-ischaemic increase in flow-rate. Neither BQ-123 nor bosentan induced significant variation in force of contraction. In ischaemic hearts, ischaemia per se induced a transient decrease in force of contraction. Bosentan significantly (P < 0.05) accentuated and BQ-123 tended to accentuate (P = 0.06) this decrease in force of contraction during ischaemia. Bosentan but not BQ-123 significantly impaired the recovery of systolic function during reperfusion (P < 0.05). Both BQ-123 and bosentan perfusion increased ET-1 efflux rate to 730 +/- 188% and 315 +/- 81% respectively. This effect was abolished during ischaemia for BQ-123, but not for bosentan. CONCLUSIONS: In isolated perfused rat hearts, both BQ-123 and bosentan increased ET-1 efflux, but only BQ-123 exerted vasoconstrictor effects. These results thus generated the hypothesis that: (1) ET-1 release within the coronary vascular bed may be physiologically subject to negative feedback regulation mediated via ETA receptors; (2) ETA receptor antagonists increase ET-1 efflux, which may lead to net vasoconstriction via unopposed ETB stimulation. Furthermore, the negative inotropic effects observed during ischaemia suggest that ET is critical to the maintenance of systolic function during ischaemia.

Effect of ischaemia and role of eicosanoids in release of atrial natriuretic factor from rat heart.

OBJECTIVE: The aim was to investigate (1) the relationship between atrial natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the potential role of eicosanoids in ANF release during global ischaemia, particularly the cyclo-oxygenase derivatives (prostaglandins) and the lipoxygenase derivatives (leukotrienes). METHODS: Using an isolated perfused, spontaneously beating rat heart, global ischaemia was achieved by the reduction of perfusion flow rate relative to basal flow rate. ANF was measured by radioimmunoassay. RESULTS: A decrease in perfusion flow rate by 75-80% to a final value of 2-2.5 ml.min-1.g-1 heart (n = 6) caused a gradual but sustained increase of ANF release which reached a plateau after 12 min, attaining a peak value of 89.9 (SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60% (n = 5) also resulted in an increased ANF secretion, with a peak of 125.6(23.2)% over baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value of 5-6.75 ml.min-1.g-1 heart (n = 4) showed no change in ANF release. The mean basal value of ANF release was 8.23(2.39) ng.min-1.g-1 heart (n = 26). In a separate series of experiments using a reduction of 55-60% in perfusion flow rate but with the addition to the perfusion medium of the specific cyclo-oxygenase inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred during the period of global ischaemia. Neither inhibitor affected ANF release during basal perfusion rates (7-9 ml.min-1.g-1 heart). CONCLUSIONS: ANF released in response to global ischaemia is likely to be mediated by prostanoids generated via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase pathway. Both pathways may provide important paracrine/autacoid regulatory roles for the protection of the heart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately leading to a reduction in load on the heart.

Inhibition of calcium uptake by somatostatin in isolated rat islets of Langerhans.

Somatostatin (1 mug/ml) inhibited glucose (16.7 mM)-stimulated 45Ca uptake by isolated rat islets incubated in media containing no added calcium or calcium at a low concentration (0.2mM). Epinephrine (50 mug/ml) and mannoheptulose (20mM) also inhibited 45Ca uptake by islets incubated in the presence of calcium (0.2mM). Addition of glucose (16.7 mM) caused a small but significant increase in insulin release from islets incubated in media containing no added calcium. In the presence of a low concentration of calcium (0.2 mM), glucose caused a much greater increase in insulin secretion which was inhibited by addition of somatostatin, epinephrine or mannoheptulose.

The effect of somatostatin on the activation of adenosine 3',5'-monophosphate-dependent protein kinase in isolated rat islets of Langerhans.

Somatostatin has been reported to inhibit the increases in cAMP levels induced by glucagon in isolated islets of Langerhans. The present study was undertaken to test whether the reported effects of somatostatin on islet cAMP levels were also reflected in changes in the cAMP-dependent protein kinase activity. Isolated islets were found to contain both isoenzymes of the cAMP-dependent protein kinase. In the presence of theophylline (2 mM), glucagon (2.9 X 10(-6) M) increased the islet protein kinase activity ratio from 0.24 +/- 0.02 to 0.55 +/- 0.02. Somatostatin (6.6 X 10(-7) M) fully inhibited both the glucagon (2.9 X 10(-7) M)- and theophylline (2 mM)-induced increases in the protein kinase activity ratio. Omission of Ca2+ from the islet incubation media did not alter the inhibitory effect of somatostatin on the glucagon-dependent activation of the cAMP-dependent protein kinase. The present study has demonstrated that in the islets of Langerhans, glucagon-dependent activation of the cAMP-dependent protein kinase can be modulated by somatostatin.

The effect of cysteamine, cystamine, and the structurally related compounds taurine, N-acetyl-cysteine, and D-penicillamine on plasma prolactin levels in normal and estrogen-primed hyperprolactinemic rats.

Studies were undertaken to evaluate the effects of cysteamine (CSH), cystamine (CS-S), N-acetyl-cysteine, D-penicillamine, and a major metabolite of CSh, taurine, on plasma PRL levels in normal and estrogen-primed hyperprolactinemic rats. Both CSH and CS-S caused a marked decrease in plasma PRL concentration in hyperprolactinemic rats. The effects of CSH and CS-S lasted for at least 6 h but returned toward pretreatment levels 24 h later. In normal rats a fall in basal plasma PRL concentration was not readily observed but after stimulation with TRH or metaclopramide, PRL secretion elicited by these stimuli was markedly inhibited by CSH and CS-S. The response to TRH or MCP 24 h after treatment with CSH was variable with CS-S appearing to cause an unexpected increase in PRL release in response to TRH or metaclopramide. The structurally related compounds, taurine, N-acetyl-cysteine, and D-penicillamine did not cause any reduction of plasma PRL levels in hyperprolactinemic rats. This may be due, in the case of taurine, to a loss of the free sulfydryl group, in the case of N-acetyl-cysteine, a change in basicity because of a carboxyl group and derivatization of the amino group and D-penicillamine, again a change in basicity due to a free carboxyl group as well as an altered structural relationship between the free amino and sulfydryl groups. These studies indicate that CSH and CS-S by possible reduction to CSH cause a reversible depletion in plasma PRL in normal and hyperprolactinemic rats. Because both substances inhibit different receptor-mediated stimuli, their mechanism of action is likely to be mediated at a common locus involved with the synthesis and release of PRL.

Pulsatility of immunoreactive somatomedin-C in chronically cannulated rats.

Pituitary GH secretion is pulsatile in man and the rat, but evidence of pulsatility in the GH-dependent somatomedins (insulin-like growth factors) has not been described. In this study serum immunoreactive somatomedin-C periodicity was examined in 10 chronically cannulated unstressed rats. Blood samples were taken at 15-min intervals over 6 h, and serum rat GH and somatomedin-C measured by RIA. For somatomedin-C assay samples were first extracted into acid-ethanol to dissociate protein-bound peptide. Serum GH levels indicated episodic secretion, with a frequency of 2.85 +/- 0.24 h; some secretory episodes were polyphasic. The mean frequency of all GH spikes reaching 400 ng/ml or greater was 1.99 +/- 0.87 h. Somatomedin-C levels showed fluctuations over an average 2-fold concentration range, 0.60 +/- 0.20 to 1.21 +/- 0.29 U/ml (mean, 0.86 +/- 0.18 U/ml), with peaks occurring 1-1.5 h after most GH secretory peaks. The somatomedin-C peak frequency was 1.93 +/- 0.47 h. Summed GH values from 0-5 h were significantly correlated with summed somatomedin-C values from 1-6 h (r = 0.861, P = 0.0007), suggesting a 1-h lag between GH pulses and the following rise in somatomedin-C. Somatomedin-binding protein showed no regular fluctuations. This study indicates that serum somatomedin-C levels in unstressed rats show periodicity which may be directly related to pulsatile GH secretion.

Prostaglandin F2 alpha mediates platelet-activating factor-stimulated atrial natriuretic factor release from the isolated rat heart.

Platelet-activating factor (PAF) and the prostaglandins have recently been shown to stimulate atrial natriuretic factor (ANF) secretion from the heart. As PAF also potentiates the release of cyclooxygenase products from isolated hearts, the role of these substances in PAF-induced ANF secretion was investigated. Using an isolated perfused rat heart preparation, cyclooxygenase inhibition by indomethacin or meclofenamic acid (10 microM for each) significantly attenuated the rise in ANF associated with PAF administration (2.5 nmol). Prostaglandin F2 alpha (PGF) produced an immediate and dose-dependent increase in ANF secretion, which was significant at 0.01 mumol and reached 348 +/- 66% over baseline values after a 1-mumol injection. Prostaglandin E2 (PGE) generated a much smaller 98 +/- 25% increase after a 1-mumol administration. Furthermore, PGF but not PGE was released from isolated hearts immediately after PAF administration. PGF release reached a maximum of 0.06 nmol/min g Heart-1 1 min after PAF stimulation and had returned to undetectable baseline values by 6 min. Cyclooxygenase inhibition abolished the release of PGF after PAF, in addition to attenuating (by 60-70%) the increased secretion of ANF after PAF injection. These results demonstrate very clearly that PGF is the major mediator for PAF-stimulated ANF secretion. Such an interaction may provide an alternative mechanism to atrial distension for the secretion of ANF in pathologies such as myocardial infarction, where autacoids such as PAF and the PGs are released from damaged cardiac muscle and elevated plasma levels of ANF are observed.

Effect of dietary salt on hemodynamics of established renal hypertension in the rabbit. Implications for the autoregulation theory of hypertension.

Two groups of 10 rabbits were subjected to renal cellophane wrapping and sham operation. Their initial mean arterial pressures (MAP) were similar, 92 +/- 1.5 and 90 +/- 2.9 mm Hg. Six weeks later three experimental periods began, each of 2 weeks' duration, on low, normal, and high salt (1, 9, and 50 mmole Na/100 g food) diets. Each group had two subgroups: rabbits with both kidneys, and rabbits with only one kidney and previous nephrectomy. The hemodynamic findings were similar in each group. After sham operation, the range of dietary salt produced no significant circulatory changes. After wrapping, MAP was reduced on low compared with normal and high salt diets (122 vs 132 and 136 mm Hg; p = 0.01). This was entirely due to lowering of cardiac output (CO) on low salt; on normal and high salt CO was higher than in sham-operated rabbits. Total peripheral resistance (TPR) in the wrapped animals was unaffected by diet, i.e., 21.4, 20.5, and 21.2 units on low, normal, and high salt--about 35% above values of sham-operated rabbits. Volume-related CO changes therefore produce long-term changes in MAP without alteration in TPR, which is not in conformity with the autoregulation theory of hypertension. Evidence of impaired capacity of wrapped compared with sham-operated rabbits to handle salt included diet-related hematocrit changes, lower creatinine clearance, and some differences in renin responses to salt. Giving saralasin reduced TPR while the rabbits were on low salt; the fall was twice as great in wrapped compared with sham-operated rabbits.

Distribution of tyrosine hydroxylase and neuropeptide Y-like immunoreactive neurons in rabbit medulla oblongata, with attention to colocalization studies, presumptive adrenaline-synthesizing perikarya, and vagal preganglionic cells.

We studied the distribution, within the rabbit medulla oblongata, of neuronal cell bodies containing either tyrosine hydroxylase or neuropeptide Y-like immunoreactivity. Both avidin-biotin and immunofluorescence procedures were used. Because the two primary antibodies were raised in different species it was possible to perform simultaneous colocalization studies with the immunofluorescence procedure. Tyrosine hydroxylase-containing neurons in the rostral medulla were demonstrated to contain a catecholamine by the colchicine-enhanced FAGLU (formaldehyde-glutaraldehyde) fluorescence histochemical procedure. These neurons are presumably adrenergic, corresponding to the C1 and C2 groups described in the rat. No C3 group was found in the rabbit. The distribution of tyrosine hydroxylase-containing neurons in the caudal medulla was in accordance with previous descriptions of the A1 and A2 groups based on the unenhanced FAGLU procedure. Neuropeptide Y-like immunoreactivity was observed in cell groups corresponding to those already described in the rat, but additional groups were discovered in the rabbit. Some neurons containing neuropeptide Y-like immunoreactivity were observed in nucleus raphe pallidus and these also contained serotonin (5-HT). In the nearby nucleus reticularis gigantocellularis there were occasional neurons that contained neuropeptide Y-like immunoreactivity without any colocalized 5-HT. Neuropeptide Y-like immunoreactivity was also observed in the dorsal motor nucleus of the vagus, rostral to the obex, and these neurons were demonstrated to be true vagal preganglionic cells by colocalization of neuropeptide Y-like immunoreactivity and Fast Blue retrogradely transported from the cervical vagus. We found that neuropeptide Y-like immunoreactivity was colocalized in approximately 75% of the tyrosine hydroxylase-containing neurons in the rostral medulla (C1 and C2 cells). A smaller proportion of the A1 cells also contained this peptide but it was absent from both the most caudal A1 cells and from the A2 cells. Some tyrosine hydroxylase-containing neurons occur in direct apposition to vagal preganglionic cells in both the dorsal motor nucleus of the vagus and the nucleus ambiguous. However, colocalization studies revealed that none of these neurons contained Fast Blue when this dye was retrogradely transported from the cervical vagus. Medullary catecholamine-synthesizing neurons apparently do not contribute axons to the vagus nerve. This finding is consistent with our own studies in the rat but is in contrast to studies in this species published by other workers.

Time-course of changes in plasma lipids in diabetic rats fed diets high in fish or safflower oils.

Adult male rats were maintained for 10 days on a standard chow diet or that diet supplemented with either safflower or marine fish oils, and then rendered diabetic with streptozotocin (40 mg/kg of body weight) and circulating metabolites determined over the next 3 days. Pre-diabetic concentrations of glucose and insulin did not differ between groups, and the severity of hyperglycaemia and lowering of insulin in streptozotocin-treated animals were also similar. Pre-diabetic concentrations of plasma free fatty acids and triacylglycerols were lower, and blood ketone bodies were higher in non-diabetic rats fed fish oil than in both other groups. However, following streptozotocin treatment, plasma free fatty acids rose significantly more in both groups of oil-fed animals than in chow-fed ones. Plasma triacylglycerols were unaltered from pre-treatment levels in rats fed chow, but rose considerably in both groups fed oil-supplemented diets. In a subsequent experiment it was shown that the increase in triacylglycerols persisted for up to 11 days after streptozotocin and the hypertriglyceridaemia was greatest in the fish oil group. The rise would seem to result from defective clearance of lipoproteins of dietary origin. It appears that fish oil-supplemented diets should be avoided in diabetics until the possibility of increased hypertriglyceridaemia has been excluded by controlled studies.

The distribution of neuropeptide Y-like immunoreactive neurons in the human medulla oblongata.

We have described the distribution of neuropeptide Y-like immunoreactive neurons in the medulla oblongata of the adult human. The majority of neuropeptide Y-like immunoreactive cells were found in four regions of the medulla: the ventrolateral reticular formation, the dorsomedial medulla, the secondary sensory nuclei and the rostral raphe nuclei. The morphology of neuropeptide Y-like immunoreactive cells varied in each of these regions. In the ventrolateral reticular formation, the labelled neurons were round and pigmented caudal to the obex but elongated and non-pigmented rostral to the obex; in the dorsomedial medulla, they were triangular and pigmented caudal to but not rostral to the obex; in the secondary sensory nuclei, they were multipolar, non-pigmented and significantly smaller than in the other areas; in the rostral raphe nuclei, they were bipolar and non-pigmented. Colocalization studies revealed that many neuropeptide Y-like immunoreactive cells also synthesize monoamines, consistent with conclusions based on a quantitative comparison of their distributions. Neuropeptide Y-like immunoreactivity was present in about 25% of presumed noradrenaline-synthesizing cells in the caudal ventrolateral medulla (corresponding to the A1 region); about 50% of adrenaline- and 70% of presumed serotonin-synthesizing cells in the rostral ventrolateral medulla (C1 and B2-3 regions); 90-100% of presumed noradrenaline-synthesizing cells in the dorsomedial medulla at and above the obex (A2 region); about 50% of adrenaline-synthesizing cells in the rostral dorsomedial medulla (C2 region); about 5% of presumed serotonin-synthesizing cells in the rostral raphe nuclei (B2-3 region). The largest of these groups was the presumed serotonin-synthesizing cells that contained neuropeptide Y-like immunoreactivity in the rostral ventrolateral medulla. This is the first report of such a cell group in the medulla of any mammal, and emphasizes the neuroanatomical differences between humans and other species.

Somatostatin is contained in and released from cholinergic nerves in the heart of the toad Bufo marinus.

The heart of the toad Bufo marinus contained a substance with somatostatin-like immunoreactivity which eluted with somatostatin on reverse phase high pressure liquid chromatography. Immunoreactivity to somatostatin was localised histochemically to nerve fibers in muscle bundles of the sinus venosus, atria and ventricles and to nerve cell bodies in the sinus venosus and inter-atrial septum. Nerve cell bodies were localised both by interference contrast microscopy and immunohistochemistry; all detectable intracardiac neurons were immunoreactive. Synthetic somatostatin inhibited the rate and force of beat of atrial preparations, but did not affect the driven ventricle. Vagal stimulation caused inhibition of all cardiac chambers. After muscarinic blockade with hyoscine, vagal stimulation with 3 Hz or more still caused inhibition of the pacemaker and atrium, but not of the ventricle. The hyoscine-resistant vagal effects were diminished by about 60% after induction of tachyphylaxis to somatostatin. When when the vagus nerves were stimulated intermittently for 1 h at 10 Hz, in the presence or absence of hyoscine, the effect of somatostatin was reduced by about 60%. It is concluded that the cholinergic postganglionic neurons of the cardiac vagus contain somatostatin. When the vagus is stimulated at 3 Hz or more, the neurons release sufficient somatostatin to inhibit the pacemaker and atrial muscle.

The depletion of plasma prolactin by pantethine in oestrogen-primed hyperprolactinaemic rats.

Pantethine was investigated for its potential to deplete prolactin in the plasma and pituitary cells of oestrogen-primed hyperprolactinaemic rats. This compound has been used in the past to deliver cysteamine systemically, through its congener pantetheine, a metabolic precursor for cysteamine. Cysteamine itself, specifically reduces plasma and pituitary prolactin. The addition of pantethine (2-10 mmol/l) to the media of isolated pituitary cells over 4 h did not appreciably alter the intracellular content of immunoreactive prolactin. Moreover, oral administration of pantethine at 0.5 and 1.0 g/kg body weight did not influence the concentration of immunoreactive plasma prolactin. However, the concentration of plasma prolactin fell by 48 and 67%, when pantethine was injected i.p. at 0.5 and 1.0 g/kg body weight, after 4 h. Intravenous administration of pantethine resulted in even greater losses of prolactin, in the order of 50 and 81% depletion for 0.5 and 1.0 g/kg body weight respectively and within 2 h of administration. However, cysteamine was found to be more efficacious than pantethine on a molar basis with regard to depleting the plasma concentration of prolactin in hyperprolactinaemic rats.

Possible oncostatic action of cysteamine on the pituitary glands of oestrogen-primed hyperprolactinaemic rats.

Cysteamine was investigated for its potential to reduce the size and secretion of oestrogen-primed hyperprolactinaemic rat pituitary glands. Subcutaneous administration of 80 and 120 mg cysteamine/kg significantly reduced plasma prolactin concentrations by 58 and 91% respectively, after 4h. Administration of cysteamine (60 mg s.c./kg body weight per day) for 10 days, to rats which had received an injection of 2 mg oestradiol benzoate on day 1, resulted in a significant reduction in pituitary mass (19%) and GH concentration (21%). Oral administration of 60 mg cysteamine/kg body weight to hyperprolactinaemic rats also produced a significant reduction in plasma prolactin of 94% after 2h. Oral administration of 60 mg cysteamine/kg body weight per day to rats for a 20-day period, during which they had received two injections of 2 mg oestradiol benzoate on day 1 and day 14 of treatment, resulted in a significant reduction in pituitary mass (29%) and the concentration of trunk blood prolactin concentration (35%). However, when oral cysteamine (60 mg cysteamine/kg body weight per day) was given for 20 days to rats which had been treated with 2 mg oestradiol benzoate once every 14 days over a 90-day period, it caused no change in pituitary weight, prolactin or GH concentration, or the concentration of prolactin in trunk blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cysteamine on the lysosomal enzymes of the hyperprolactinaemic rat pituitary.

The effect of cysteamine on the activity of lysosomal enzymes and the prolactin content of isolated hyperprolactinaemic cells has been investigated. In broken cell preparations, cysteamine markedly stimulated acid prolactin protease activity. In intact cells, however, cysteamine inhibited acid prolactin protease activity and beta-galactosidase. Moreover, the activities of alpha-mannosidase, acid phosphatase, beta-glucuronidase, total arylsulphatase and hexosaminidase were not changed by the addition of cysteamine. Cysteamine significantly depleted the cells of prolactin, and this action was not compromized by the inclusion of either leupeptin, chloroquine or NH4Cl in the incubation media. Taken together, these results indicate that cysteamine does not promote degradation of prolactin and hence depletion of prolactin from the pituitary through a mechanism involving lysosomal enzyme degradation.

Platelet-activating factor stimulates the release of atrial natriuretic factor from the rat heart.

Atrial natriuretic factor (alpha-ANF (99-126), ANF) is released from atrial cells following atrial distension, myocardial infarction and periods of ischaemic or tachyarrhythmias. In this report we demonstrate that platelet-activating factor (PAF) stimulates ANF release from the isolated perfused rat heart and following i.v. injection to conscious unrestrained rats. ANF release peaked at 145% above baseline following injection of 2.5 nmol PAF into the isolated heart while administration of 2 nmol in vivo produced a 135% increase in plasma ANF levels. The PAF receptor antagonist BN52021 (10 mumol/l) attenuated this stimulated release, with the results suggesting a role for PAF in ANF secretion following release from damaged myocardium or as a humoral factor originating from the kidney.

Effects of human growth hormone on the secretion of rat growth hormone.

Human growth hormone (hGH) was administered to chronically cannulated male rats and its effect upon the physiological secretory patterns of rat growth hormone (rGH) and prolactin were observed. In comparison with injected control animals, a reduction in the size of spontaneous secretory bursts of rGH was apparent when hormone concentrations were compared 3-6 h after administration of hGH (136.27 +/- 27.31 (S.E.M.) v. 76.22 +/- 20.98 ng/ml respectively). However, the mean frequency of secretory episodes of rGH was unaltered. It is therefore postulated that endogenous rGH may modulate the amplitude but not the rhythmicity of secretory episodes of rGH.