Low-set osmotic threshold for vasopressin release in a patient with prolactinoma

This report describes a 38-year-old patient with prolactinoma, without adrenal or thyroid insufficiency, with syndrome of inappropriate secretion of vasopressin due to downward resetting of the hypothalamic osmoreceptors. Random measurements of plasma and urine osmolality revealed an inappropriately high urine osmolality for a given plasma osmolality. Simultaneous plasma vasopressin levels were within normal limits. Urine dilution after water load was normal. During infusion of hypertonic saline, the osmotic threshold was demonstrated at plasma osmolality of 267 mosmol/kg, which is markedly lower than the normal 287.3 +/- 3.3 mosmol/kg. Thirst sensation seemed to be intact. The defect in the osmoreceptor function might have been induced by the tumor mass or by chronic hyperprolactinemia.     

家兔主动脉神经高阈压力感受反射性速重调中枢过程的机能特征

Experiments were performed on 37 urethane-anesthetized rabbits. The aortic nerves, carotid sinus nerves and vagus nerves were cut, MAP and renal sympathetic nerve activity (RSNA) were recorded. The conditional stimulation CSc (0.5 ms, 10 Hz, 4-6V, 5 min) was used to mimic the information of baroreflex non-medullated afferent fibers responding to acute increase of BP. Test stimulation TSa (0.02 ms, 0-80 Hz/30 s, 4-6V) and TSc (0.5 ms, 0-20 Hz/30s, 4-6V) was used to examine the responses of baroreflex A- and C-fibers. After CSc at 1 min the reflex MAP and RSNA of TSc was attenuated at 45.5% (P less than 0.01) and 10.6% (P less than 0.05), the MAP response of TSa was attenuated at 32.1% (P less than 0.05), but the RSNA response was not. From the further investigation it is concluded that the characteristics of central acute resetting are dependent on the components of baroreflex afferent fibers. The reflex responses are attenuated mainly by correspondent afferent components.     

Reset of the osmotic threshold for vasopressin in rats fed a low NaCl, K-free diet.

Activation of the renin-angiotensin system induced by feeding a low NaCl, K-free (LS) diet is associated with polydipsia and a chronic reduction in effective plasma osmolality (efPosm). We have recently shown that converting enzyme inhibition with enalapril (EP) abolishes polydipsia. The present study was designed to test the hypothesis that the osmotic threshold for vasopressin is reset in rats fed the LS diet and to examine the effect of EP on ambient and osmotically stimulated plasma vasopressin levels (PAVP). Animals were fed the LS diet or a control salt diet and treated with vehicle or the lowest dose of EP sufficient to prevent polydipsia (7.5 mg.kg-1.day-1) in rats fed the LS diet. PAVP and efPosm were measured under ambient conditions and after osmotic loading. Urine osmolality (Uosm) was measured under ambient conditions and after water loading. The chronic reduction in efPosm in LS rats was associated with the excretion of a Uosm 1-2 times greater than the corresponding Posm, PAVP similar to controls (LS, 2.27 +/- 1.08 vs. control, 1.19 +/- 0.22 pg/mL) and the ability to excrete a water load. Following osmotic loading, efPosm and PAVP increased significantly and similarly in both LS and control rats. EP administration had no effect on water intake, ambient efPosm and PAVP, and the AVP response to osmotic loading in rats fed the control diet. EP prevented polydipsia in LS rats, however it had no significant effect on ambient or osmotically stimulated PAVP or efPosm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of baroreceptor resetting in cardiovascular regulation: acute resetting

Recent studies show that the arterial baroreceptor reflex cannot be defined by a single buffer curve. The reflex blood pressure and heart rate curves depend on the pressure to which the baroreceptors are exposed. If arterial pressure is elevated for longer than 3-5 min the threshold and the entire buffer curve are shifted to higher pressures. On the other hand, a reduced arterial pressure shifts the buffer curve to lower pressures. Part of this phenomenon, which has been called rapid or acute resetting, may be explained by changes in the baroreceptor discharge in response to exposure to sustained alterations in pressure. The reflex response, however, resets more than can be explained by changes in the baroreceptor discharge. A central component to the resetting process is suggested. Resetting allows the baroreceptor reflex to operate over a wide range of arterial pressures rather than being confined to a single range defined by one buffer curve. Resetting is not complete. That is, if the receptors are exposed to a change in pressure of 30 mm Hg the buffer curves shift by less than 30 mm Hg. Thus a signal concerning mean pressure is not eliminated by the resetting process.     

Suppression of thirst in dogs with arteriovenous fistula

The aim of the present study was to investigate the effect of moderate continuous overloading of the heart on 24-h water intake (WI), urine (Vu), sodium (UNaV), potassium (UKV), solute (Cosm) and free water (CH20) excretion. The overloading of heart was produced by construction of the fistula (AVF) between the femoral artery and the vena cava inferior. Twenty four hours WI, Vu, UNaV, UKV, Cosm, CH20, as well as central venous (CVP), arterial (MABP) and interstitial (IP) pressure and volume of the extracellular fluid (ECW) were examined before and 1, 2 or 3 months after production of AVF. Daily water intake, and water/food ratio decreased, whereas CVP, MABP and IP increased significantly after production of the fistula. A significant increase in ECW was found 1 month after production of AVF. It is suggested that a moderate overloading of the heart may cause a prolonged decrease in water intake, possibly due to augmentation of the inhibitory input from the cardiovascular receptors.     

Glycaemic threshold for changes in electroencephalograms during hypoglycaemia in patients with insulin dependent diabetes

The relation between blood glucose concentration, the symptoms and signs of hypoglycaemia, and electroencephalographic changes in diabetic patients is not known. The effect of hypoglycaemia on brain function was studied in 13 patients with insulin dependent diabetes. During a gradual fall in blood glucose concentration induced by a bolus injection of insulin followed by an intravenous infusion of insulin, during 60 minutes of biochemical hypoglycaemia, and after restoration of normoglycaemia with intravenous glucose electroencephalograms were evaluated continuously by period-amplitude analysis; blood samples were taken every 10 minutes throughout. No changes were seen in electroencephalograms when the blood glucose concentration was above 3 mmol/l. At a median blood glucose concentration of 2·0 (95% confidence interval 1·7 to 2·3) mmol/l alpha activity decreased abruptly in the electroencephalograms concomitant with an increase in theta activity, reflecting neuronal dysfunction in the cortex. When the blood glucose concentration was further lowered changes were observed in the electroencephalograms indicating that deeper brain structures were affected. A normal electroencephalogram was re-established at a blood glucose concentration of 2·0 (1·8 to 2·1) mmol/l. There was no significant correlation between the blood glucose concentration at the onset of changes in the electroencephalograms and age, duration of diabetes, insulin dose, haemoglobin A_1c concentration, initial blood glucose concentration, rate of fall in blood glucose concentration, and appearance of symptoms and signs of hypoglycaemia.Changes in electroencephalograms during hypoglycaemia appear and disappear at such a narrow range of blood glucose concentrations that the term threshold blood glucose concentration for the onset of such changes seems justified.     

Phase resetting associated with changes of burst shape

Based on our stochastic approach to phase resetting of an ensemble of oscillators, in this article we investigate two stimulation mechanisms which exhibit qualitatively different dynamical behaviour as compared with the stimulation mechanism analysed in a previous study. Both the old as well as one of the new stimulation mechanisms give rise to a characteristic desynchronization behaviour: A stimulus of a given (non-vanishing) intensity administered at a critical initial ensemble phase for a critical duration T _crit annihilates the ensemble's synchronized oscillation. When the stimulation duration exceeds T _crit a transition from type 1 resetting to type 0 resetting occurs. The second new stimulation mechanism does not cause a desynchronization which is connected with a phase singularity. Correspondingly this mechanism only leads to type 1 resetting. In contrast to the stimulation mechanism analysed in a previous study, both new stimulation mechanisms cause burst splitting. According to our results, in this case peak or onset detection algorithms are not able to reveal a correct estimate of the ensemble phase. Thus, whenever stimulation induced burst splitting occurs, phase-resetting curves determined by means of peak or onset detection may be nothing but artifacts. Therefore it is necessary to understand burst splitting in order to develop reliable phase detection algorithms, which are e.g. based on detecting bursts' centers of mass. Our results are important for experimentalists: Burst splitting is, for instance, well-known from tremor resetting experiments. Thus, it often turned out to be at least rather difficult to derive reliable phase-resetting curves from experimental data.     

In search of the pathways for light-induced pacemaker resetting in the suprachiasmatic nucleus

Within the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is a circadian pacemaker that functions as a clock. Its endogenous period is adjusted to the external 24-h light-dark cycle, primarily by light-induced phase shifts that reset the pacemaker's oscillation. Evidence using a wide variety of neurobiological and molecular genetic tools has elucidated key elements that comprise the visual input pathway for SCN photoentrainment in rodents. Important questions remain regarding the intracellular signals that reset the autoregulatory molecular loop within photoresponsive cells in the SCN's retino-recipient subdivision, as well as the intercellular coupling mechanisms that enable SCN tissue to generate phase shifts of overt behavioral and physiological circadian rhythms such as locomotion and SCN neuronal firing rate. Multiple neurotransmitters, protein kinases, and photoinducible genes add to system complexity, and we still do not fully understand how dawn and dusk light pulses ultimately produce bidirectional, advancing and delaying phase shifts for pacemaker entrainment.     

Analysis of the impulse activity of the cerebral neurons in rabbits with artificial thirst

Neuronal impulse activity of various brain structures was studied in rabbits in conditions of artificial thirst elicited by intrabrain injection of 0.3-0.5 M NaCl solution (from 5 to 8 mcl). Specific organization was revealed of the impulse flow at drinking motivational excitation, i.e., domination on interval histograms of certain intervals (20-40 and 100-200 ms). Comparative analysis of activity patterns of both different and the same neurones in conditions of natural and artificial thirst showed a resemblance of dominating intervals values that testifies to specificity of the observed neural activity characteristics, reflecting drinking motivational excitation. Thus, an interval code is found corresponding to drinking motivational state. P. K. Anokhin's notions about anticipating reflection of reality find their expression in anticipating reactions of brain neuronal activity.     

Global environmental costs of China's thirst for milk

China has an ever‐increasing thirst for milk, with a predicted 3.2‐fold increase in demand by 2050 compared to the production level in 2010. What are the environmental implications of meeting this demand, and what is the preferred pathway? We addressed these questions by using a nexus approach, to examine the interdependencies of increasing milk consumption in China by 2050 and its global impacts, under different scenarios of domestic milk production and importation. Meeting China's milk demand in a business as usual scenario will increase global dairy‐related (China and the leading milk exporting regions) greenhouse gas (GHG) emissions by 35% (from 565 to 764 Tg CO_2eq) and land use for dairy feed production by 32% (from 84 to 111 million ha) compared to 2010, while reactive nitrogen losses from the dairy sector will increase by 48% (from 3.6 to 5.4 Tg nitrogen). Producing all additional milk in China with current technology will greatly increase animal feed import; from 1.9 to 8.5 Tg for concentrates and from 1.0 to 6.2 Tg for forage (alfalfa). In addition, it will increase domestic dairy related GHG emissions by 2.2 times compared to 2010 levels. Importing the extra milk will transfer the environmental burden from China to milk exporting countries; current dairy exporting countries may be unable to produce all additional milk due to physical limitations or environmental preferences/legislation. For example, the farmland area for cattle‐feed production in New Zealand would have to increase by more than 57% (1.3 million ha) and that in Europe by more than 39% (15 million ha), while GHG emissions and nitrogen losses would increase roughly proportionally with the increase of farmland in both regions. We propose that a more sustainable dairy future will rely on high milk demanding regions (such as China) improving their domestic milk and feed production efficiencies up to the level of leading milk producing countries. This will decrease the global dairy related GHG emissions and land use by 12% (90 Tg CO_2eq reduction) and 30% (34 million ha land reduction) compared to the business as usual scenario, respectively. However, this still represents an increase in total GHG emissions of 19% whereas land use will decrease by 8% when compared with 2010 levels, respectively.     

Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus.

Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T(or) between groups (P > 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 +/- 0.07 degrees C in controls and 36.55 +/- 0.05 degrees C in T2DM patients (P < 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P > 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM.     

Peptide-protein complexes of angiotensins in the mechanisms of thirst

The comparative analysis of learned and natural drinking behavior under native angiotensin-I (A-I), angiotensin-II (A-II) and its protein-peptides complexes (PPC) administration in rats, was performed. Various effects of these substances on drinking behavior were observed. PPC of A-I became a dipsogenic agent as compared with the native one. Moreover, PPC of A-II facilitated selectively learned and not natural forms of drinking behavior. It's suggested that PPC of angiotensins play a specific role in endogenous mechanisms of thirst. An important function of this complexes due to their conformational properties and participation in realization of basic needs, is discussed.