David Jessop

Substance P Inhibits the Release of Anterior Pituitary Adrenocorticotrophin via a Central Mechanism Involving Corticotrophin‐Releasing Factor‐Containing Neurons in the Hypothalamic Paraventricular Nucleus

Chronic osmotic stimulation influences the hypothalamo‐adenohypophysial axis by inhibiting the synthesis of hypothalamic corticotrophin‐releasing factor (CRF‐41) and subsequently the secretion of basal and adrenalectomy‐elevated adrenocorticotrophin from the adenohypophysis. In the present study, we used a substance P antagonist to test the hypothesis that this inhibition is mediated centrally by substance P or other tachykinins. In control rats and rats given 2% saline to drink for 12 days, intracerebroventricular administration of a substance P antagonist elevated plasma adrenocorticotrophin and corticosterone levels. Using quantitative in situ hybridization histochemistry, it was also demonstrated that CRF mRNA increased in the medial parvocellular division of the paraventricular nucleus of saline‐treated as well as control rats 6 h after intracerebroventricular administration of the antagonist, while vasopressin mRNA in the medial parvocellular division of the paraventricular nucleus was increased in the control animals only. These results provide evidence that central endogenous substance P has an inhibitory influence over the synthesis and release of CRF‐41 both under normal conditions and during a chronic osmotic stimulus.

Higher physical activity is associated with increased androgens, low interleukin 6 and less aortic calcification in peripheral obese elderly women

The presence of peripheral fat mass (PFM) appears to counteract the atherogenic trends of central fat mass through mechanisms presently poorly understood. In elderly women with distinct forms of body fat distribution, we wanted to study whether physical activity and aortic calcification are related to plasma levels of cortisol, 17-alpha-hydroxyprogesterone (17-alpha-OHP), dehydroepiandrosterone (DHEA), androstenedione (ASD), and interleukin 6 (IL6) accomplishing an anti-atherogenic milieu. A total of 276 well-defined generally healthy women aged 60-85 years were included. Categorization of body fat distribution was based on the relative presence of central to PFM measured by dual-energy X-ray absorptiometry. Women meticulously reported weekly physical activity. Outcome measures were aortic calcification between lumbar vertebra L1 and L4, plasma levels of hormones, and IL6. In peripheral adipose women, plasma DHEA and ASD increased with the degree of physical activity. This was also mirrored in the ratios of cortisol/DHEA and cortisol/17-alpha-OHP. Peripheral adipose women with high DHEA relative to cortisol had less severe aortic calcification, and in the same group a higher level of physical activity was associated with lower levels of plasma IL6. In conclusion, this study demonstrates that high physical activity is associated with a high circulating androgen to cortisol ratio, low IL6, and less severe aortic calcification. Since androgens inhibit IL6 secretion, the activity-induced increase of these hormones might be an anti-atherogenic signal.

Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis.

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.

Osmotic regulation of methionine enkephalin in the posterior pituitary of the rat

Methionine (Met) enkephalin is detectable in rat hypothalamic and neurointermediate lobe (NIL) tissue extracts using a specific radioimmunoassay. Reversed-phase HPLC revealed that only the pentapeptide form was present in the extracts. Total amounts of Met-enkephalin in extracts containing the median eminence (ME), supraoptic nucleus (SON), paraventricular nucleus (PVN), or NIL from control animals were 9.7 +/- 1.6, 0.9 +/- 0.2, 25.2 +/- 6.8 and 14.8 +/- 1.2 pmol respectively (means +/- S.E.M., n = 6). In animals given 340 mmol NaCl/l to drink for 5 days, no significant changes occurred in Met-enkephalin content in the SON or ME, but significant decreases were observed in the NIL and PVN (9.8 +/- 0.8 and 13.6 +/- 1.7 pmol, respectively). Amounts of Met-enkephalin in these tissues were further decreased after 12 days of 340 mmol NaCl/l (3.4 +/- 0.4 and 6.0 +/- 0.6 pmol). These data demonstrate that enkephalin immunoreactivity in the NIL is principally in the form of the Met-enkephalin pentapeptide, and that this peptide is released in response to increased plasma osmolality. The concomitant changes in the PVN and NIL tissue content suggest that the PVN is the source of NIL Met-enkephalin.

Effects of particle mixtures and nozzle geometry on entrainment into volcanic jets

Efficient turbulent entrainment causes otherwise dense volcanic jets to rise high into the atmosphere as buoyant plumes. Classical models suggest that the inflow of air is 10–15% of the axial velocity, giving predictions for the height of the plume and, in turn, the composition and structure of the resulting umbrella clouds. Crucially, entrainment is assumed independent of source geometry and mechanically unaffected by the pyroclastic mixture properties. We show that particle inertia and vent geometry act to modify the shape of the largest eddies defining the jets edge and thus entrainment of the ambient. Whereas particle-free flows are essentially unaffected by vent shape, entrainment into particle-laden flows is enhanced for flared vents and reduced for cylindrical vents. Our results predict that vent erosion during an explosive eruption reduces the height of volcanic jets, alters the structure and sedimentation regime of the umbrella cloud, and the resulting deposit.

The effects of gas flow on granular currents.

Currents of particles have been quite successfully modelled using techniques developed for fluid gravity currents. These models require the rheology of the currents to be specified, which is determined by the interaction between particles. For relatively small slow currents, this is determined primarily through friction, which can be controlled and reduced by fluidizing the particles, so that they may become much more mobile. Recent results cannot be predicted using many of the proposed models, and may be defined by the interaction between the particles and the fluid through which they are passing. However, in addition, particles that are only initially fluidized also form currents that are also mobile, but otherwise are different from continuously fluidized currents. The mobility of these currents appears not to be connected to the time taken for them to degas. This suggests that defining the continuous stresses on the particle current may not be sufficient to understand its motion and that a challenge for the future is to understand the structure of these flows and how this affects their motion.

Chronic citalopram treatment does not sensitize the adrenal gland to ACTH (1-24) in rats.

We have previously reported that rats exposed chronically to citalopram are able to elicit a corticosterone but not adrenocorticotropic hormone (ACTH) response to restraint stress. Thus we proposed the hypothesis that the corticosterone response to restraint in citalopram-treated rats was maintained due to increased adrenal sensitivity to lower ACTH levels. To test this hypothesis, we intravenously injected ACTH (1—24) to rats (dose 3 ng/rat) exposed to citalopram through minipump infusion for 14 days and to control rats (no citalopram). ACTH significantly increased plasma corticosterone levels in both control and citalopram treated rats over a period of 120 min. There was no significant difference in plasma corticosterone between citalopram treated rats and control rats at any time point. Therefore we conclude that, under these experimental conditions, citalopram does not appear to sensitize the rodent adrenal gland to ACTH, and that other mechanisms may be responsible for the ACTH/corticosterone disconnection.

‘Neuropsychopharmacology of Stress’: Advances at the Turn of the Millennium

Stress is very much a high profile issue in todays world. While an acute response to immediate environmental change is both necessary and advantageous in dealing with the myriad challenges of everyday living, inappropriate physiological responses associated with chronic stress can be damaging and life-threatening.

Steady and unsteady fluidised granular flows down slopes

Fluidisation is the process by which the weight of a bed of particles is supported by a gas flow passing through it from below. When fluidised materials flow down an incline, the dynamics of the motion differ from their non-fluidised counterparts because the granular agitation is no longer required to support the weight of the flowing layer. Instead, the weight is borne by the imposed gas flow and this leads to a greatly increased flow mobility. In this paper, a framework is developed to model this two phase motion by incorporating a kinetic theory description for the particulate stresses generated by the flow. In addition to calculating numerical solutions for fully developed flows, it is shown that for sufficiently thick flows there is often a local balance between the production and dissipation of the granular temperature. This phenomenon permits an asymptotic reduction of the full governing equations and the identification of a simple state in which the volume fraction of the flow is uniform. The results of the model are compared with new experimental measurements of the internal velocity profiles of steady granular flows down slopes. The distance covered with time by unsteady granular flows down slopes and along horizontal surfaces and their shapes are also measured and compared with theoretical predictions developed for flows that are thin relative to their streamwise extent. For the horizontal flows, it was found that resistance from the sidewalls was required in addition to basal resistance to capture accurately the unsteady evolution of the front position and the depth of the current and for situations in which side-wall drag dominates, similarity solutions are found for the experimentally-measured motion.