Elevated Plasma Osmolality Research Articles

Physiological assessment of the effects of experimental capture and transport in Pacific spiny dogfish

Sharks are collected from the wild as live specimens for display in aquariums and use in research. The methods by which live sharks are captured and transported can be associated with sub-lethal physiological outcomes or even mortality, which requires evaluation to determine optimal collection and transport methods for a given species. The present study evaluated the primary (i.e., endocrine) and secondary (i.e., biochemical) stress responses and mortality in Pacific spiny dogfish (Squalus suckleyi) following capture and subsequent transport between experimental rod-and-reel angling and longline fishing. Dogfish were resilient to transport following capture by either method, exhibiting no at-vessel mortality and 0.03% delayed mortality. Longline captured dogfish exhibited signs of primary (i.e., elevated corticosterone) and secondary (i.e., elevated plasma potassium, osmolality, glucose, and lactate; decreased blood pH) stress responses, whereas dogfish that experienced rod-and-reel capture and transport only exhibited a secondary stress response (i.e., elevated plasma potassium, osmolality, and lactate; decreased blood pH). Together, these data demonstrate that Pacific spiny dogfish are robust to capture and transport using experimental hook-and-line fishing techniques.

Compositional Aspects of Beverages Designed to Promote Hydration Before, During, and After Exercise: Concepts Revisited.

Hypohydration can impair aerobic performance and deteriorate cognitive function during exercise. To minimize hypohydration, athletes are recommended to commence exercise at least euhydrated, ingest fluids containing sodium during long-duration and/or high-intensity exercise to prevent body mass loss over 2% and maintain elevated plasma osmolality, and rapidly restore and retain fluid and electrolyte homeostasis before a second exercise session. To achieve these goals, the compositions of the fluids consumed are key; however, it remains unclear what can be considered an optimal formulation for a hydration beverage in different settings. While carbohydrate-electrolyte solutions such as sports drinks have been extensively explored as a source of carbohydrates to meet fuel demands during intense and long-duration exercise, these formulas might not be ideal in situations where fluid and electrolyte balance is impaired, such as practicing exercise in the heat. Alternately, hypotonic compositions consisting of moderate to high levels of electrolytes (i.e., ≥45 mmol/L), mainly sodium, combined with low amounts of carbohydrates (i.e., <6%) might be useful to accelerate intestinal water absorption, maintain plasma volume and osmolality during exercise, and improve fluid retention during recovery. Future studies should compare hypotonic formulas and sports drinks in different exercise settings, evaluating different levels of sodium and/or other electrolytes, blends of carbohydrates, and novel ingredients for addressing hydration and rehydration before, during, and after exercise.

Prolactin-secreting Pituitary Macro-adenoma Presenting with Mass Effects, Hormonal Deficiencies, and Neurogenic Diabetes Insipidus: A Case Report and Review of Literature

To report and review a case of prolactin-producing pituitary tumor presenting with mass effects, hormonal deficiency, and neurogenic diabetes insipidus in a nulliparous woman of Afro-Caribbean descent. The patient presented with dull-aching headaches associated with worsening vision, nausea, and vomiting. The patient also complained of polyuria, nocturia, thirst, polydipsia, and weight gain. Physical examination showed bilateral visual field defects, while investigations revealed hypernatremia and elevated plasma osmolality but decreased urine sodium concentration, osmolality, and specific gravity.&#x0D; Results of the hormonal profile showed high plasma prolactin levels, a low plasma concentration of the antidiuretic hormone, and decreased levels of other anterior pituitary hormones. Imaging revealed a large, uncalcified, cystic pituitary mass extending into adjacent structures and compressing the optic chiasm and internal carotid artery. The outcome of the water deprivation and desmopressin administration tests were consistent with neurogenic diabetes insipidus, and a diagnosis of prolactin-producing pituitary macroadenoma with mass effects, hormonal deficiencies, and neurogenic diabetes insipidus was made. The patient was commenced on medical treatment and referred for histopathological diagnosis and definitive treatment. This report highlights the coexistence of neurogenic diabetes insipidus with a prolactin-producing pituitary macroadenoma presenting with mass effects.

Magnesium transport in the aglomerular kidney of the Gulf toadfish (Opsanus beta).

Despite having an aglomerular kidney, Gulf toadfish can survive in water ranging from nearly fresh up to 70 parts per thousand salinity. In hyperosmotic environments, the major renal function is to balance the passive Mg2+ load from the environment with an equal excretion. However, the molecular transporters involved in Mg2+ secretion are poorly understood. We investigated whether environmental MgCl2 alone or in combination with elevated salinity affected transcriptional regulation of genes classically involved in renal Mg2+ secretion (slc41a1, slc41a3, cnnm3) together with three novel genes (trpm6, trpm7, claudin-19) and two isoforms of the Na+/K+-ATPase α-subunit (nka-α1a, nka-α1b). First, toadfish were acclimated to 5, 9, 35, or 60 ppt water (corresponding to ~ 7, 13, 50 and 108mmolL-1 ambient [Mg2+], respectively) and sampled at 24h or 9days. Next, the impact of elevated ambient [Mg2+] was explored by exposing toadfish to control (50mmolL-1 Mg2+), or elevated [Mg2+] (100mmolL-1) at a constant salinity for 7days. Mg2+ levels in this experiment corresponded with levels in control and hypersaline conditions in the first experiment. A salinity increase from 5 to 60 ppt stimulated the level of all investigated transcripts in the kidney. In Mg2+-exposed fish, we observed a 14-fold increase in the volume of intestinal fluids and elevated plasma osmolality and [Mg2+], suggesting osmoregulatory challenges. However, none of the renal gene targets changed expression compared with the control group. We conclude that transcriptional regulation of renal Mg2+ transporters is induced by elevated [Mg2+] in combination with salinity rather than elevated ambient [Mg2+] alone.

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry

BackgroundComplicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated.MethodsWe prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan–Meier curve analysis and Cox proportional hazard testing.Results216 (22.5%) patients reached the primary endpoint. Kaplan–Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25–23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46–21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e′, and N-terminal pro-B-type natriuretic peptide elevation.ConclusionsHigher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Association between Plasma Osmolality and Case Fatality within 1 Year after Severe Acute Ischemic Stroke.

PurposePlasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality is associated with case fatality within 1 year after severe acute ischemic stroke.Materials and MethodsWe included severe ischemic stroke patients (defined as National Institutes of Health Stroke Scale ≥15 score) within 24 hours from symptom onset admitted to the Department of Neurology, West China Hospital between January 2017 and June 2019. Admission plasma osmolality was calculated using the equation 1.86*(sodium+potassium)+1.15*glucose+urea+14. Elevated plasma osmolality was defined as plasma osmolality >296 mOsm/kg, indicating a state of dehydration. Study outcomes included 3-month and 1-year case fatalities. Multivariable logistic regression was performed to determine independent associations between plasma osmolality and case fatalities at different time points.ResultsA total of 265 patients with severe acute ischemic stroke were included. The mean age was 71.2±13.1 years, with 51.3% being males. Among the included patients, case fatalities were recorded for 31.7% (84/265) at 3 months and 39.6% (105/265) at 1 year. Elevated plasma osmolality (dehydration) was associated with 3-month case fatality [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07–3.66, p=0.029], but not 1-year case fatality (OR 1.51, 95% CI 0.84–2.72, p=0.165), after full adjustment for confounding factors.ConclusionElevated plasma osmolality was independently associated with 3-month case fatality, but not 1-year case fatality, for severe acute ischemic stroke.

Does lysine acetylation affect water permeability of the collecting duct?

We recently reported that there are &gt; 400 proteins in the inner medullary collecting duct that are post‐translationally lysine acetylated (ac‐K). Although historically, ac‐K proteins were thought to be predominantly histone proteins in the nucleus, we now know that all cellular compartments are enriched with ac‐K proteins. Pathway analyses determined that ac‐K proteins are enriched in various physiological processes such as glycolysis and vasopressin‐mediated water reabsorption. We recently identified the basolateral water channel, aquaporin‐3 (AQP3), as undergoing lysine acetylation (AQP3 K282). Thus, the purpose of this study was to determine if ac‐K AQP3 affects water permeability. We developed antibodies to specifically detected ac‐K AQP3 or total AQP3. In both male and female mice, ac‐K AQP3 was expressed in the basolateral membrane of the cortical and outer medullary collecting duct. However, following 24 h of water deprivation, ac‐K AQP3 was also found in the inner medullary collecting duct. Next, we developed AQP3 K point mutation plasmids, with K282Q representing an acetylated mimic, and K282 representing a deacetylated mimic. These constructs were stably expressed in vasopressin‐responsive mouse cortical collecting duct cells (AQP3mpkCCDs). Using the cell volume sensitive dye, calcein, water permeability of these mutant cells was determined following an osmotic stimulus. We found the acetylated mimic (K282Q) had the highest water permeability followed by the AQP3 wild type K282 cells and the deacetylated mimic (K282R). Finally, using CRISPR/CAS we engineered whole body point mutation mice. The K282Q mutant mice and littermate controls (K282) all developed normally. As adults, K282Q mice presented with elevated plasma osmolality (307 ± 2 mOsm/Kg H2O vs 298 ± 4 mOsm/kg H2O, P = 0.04) at baseline. Following 3 days of hydration with 5% sucrose water, K282Q produced twice as much urine as controls during their active period (2.16 ± 0.5 ml/12h vs 0.88 ± 0.2, P = 0.03). Moreover, when challenged with a 2 ml sterile water i.p., K282Q mice excreted majority of the water load within the first 3 h, while controls reached peak urine flow after 3 h. Finally, we quantified AQP2 (the apical water channel) and AQP3 mRNA expression and protein abundance. AQP2, AQP3 and AQP4 mRNA expression was similar between control and mutant mice. Surprisingly, K282Q mutant mice presented with significantly less AQP2 and AQP3 protein abundance compared to controls. Thus, mutating K282 in vivo resulted in a loss of AQP3 (a potentially AQP2) stability, and highlights the importance of this lysine residue. To conclude, lysine acetylation of AQP3 is a novel posttranslational modification that may regulate AQP function and water permeability in the collecting duct.Support or Funding InformationK01DK105038, R03DK120503, the University of Alabama at Birmingham Pittman Scholarship, NIH P30 DK074038

Salinity modulates biochemical and histopathological changes caused by silver nanoparticles in juvenile Persian sturgeon (Acipenser persicus).

The objective of this study was to evaluate the effect of salinity on the acute and sub-chronic toxicity of silver nanoparticles (AgNPs) in Persian sturgeon. This was evaluated by exposing Persian sturgeon to AgNPs in three salinities: freshwater (F: 0.4ppt), brackish water 1 (B1: 6 ± 0.2ppt), and brackish water 2 (B2: 12 ± 0.3ppt) for 14days, which was followed by analysis of alterations in plasma chemistry and histopathology of the gills, liver, and intestine. Values of 96-h median lethal concentration (LC50) were calculated as 0.89mg/L in F, 2.07mg/L in B1, and 1.59mg/L in B2. After sub-chronic exposures, plasma cortisol, glucose, potassium, and sodium levels illustrated no significant changes within each salinity level. In F, 0.2mg/L AgNP caused the highest levels of alkaline phosphatase and osmolality levels. In B1, 0.6mg/L AgNP induced the highest level of alkaline phosphatase and elevated plasma osmolality was recorded in all AgNP-exposed treatments in comparison with the controls. The B2 treatment combined with 0.6mg/L AgNP significantly reduced plasma chloride level. The results showed elevating salinity significantly increased osmolality, chloride, sodium, and potassium levels of plasma in the fish exposed to AgNPs. The abundance of the tissue lesions was AgNP concentration-dependent, where the highest number of damages was observed in the gills, followed by liver and intestine, respectively. The histopathological study also confirmed alterations such as degeneration of lamella, lifting of lamellar epithelium, hepatic vacuolation, pyknotic nuclei, and cellular infiltration of the lamina propria elicited by AgNPs in the gills, liver, and intestine of Persian sturgeon. In conclusion, the stability of AgNPs in aquatic environments can be regulated by changing the salinity, noting that AgNPs are more stable in low salinity waters.

Elevated plasma copeptin levels identify the presence and severity of non-alcoholic fatty liver disease in obesity

IntroductionCopeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH.MethodsFor this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific).ResultsObese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD− 6.4 ± 2.6; and non-ob/NAFLD− 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02–2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components.ConclusionsIncreased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention.

Osmoregulation in the Plotosidae Catfish: Role of the Salt Secreting Dendritic Organ.

Unlike other marine teleosts, the Plotosidae catfishes reportedly have an extra-branchial salt secreting dendritic organ (DO). Salinity acclimation [brackishwater (BW) 3aaa, seawater (SWcontrol) 34aaa, and hypersaline water (HSW) 60aaa] for 14 days was used to investigate the osmoregulatory abilities of Plotosus lineatus through measurements of blood chemistry, muscle water content (MWC), Na+/K+-ATPase (NKA) specific activity and ion transporter expression in gills, DO, kidney and intestine. Ion transporter expression was determined using immunoblotting, immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR). HSW elevated mortality, plasma osmolality and ions, and hematocrit, and decreased MWC indicating an osmoregulatory challenge. NKA specific activity and protein levels were significantly higher in DO compared to gill, kidney and intestine at all salinities. NKA specific activity increased in kidney and posterior intestine with HSW but only kidney showed correspondingly higher NKA α-subunit protein levels. Since DO mass was greater in HSW, the total amount of DO NKA activity expressed per gram fish was greater indicating higher overall capacity. Gill NKA and V-ATPase protein levels were greater with HSW acclimation but this was not reflected in NKA activity, mRNA or ionocyte abundance. BW acclimation resulted in lower NKA activity in gill, kidney and DO. Cl- levels were better regulated and the resulting strong ion ratio in BW suggests a metabolic acidosis. Elevated DO heat shock protein 70 levels in HSW fish indicate a cellular stress. Strong NKA and NKCC1 (Na+:K+:2Cl- cotransporter1) co-localization was observed in DO parenchymal cells, which was rare in gill ionocytes. NKCC1 immunoblot expression was only detected in DO, which was highest at HSW. Cystic fibrosis transmembrane regulator Cl- channel (CFTR) localize apically to DO NKA immunoreactive cells. Taken together, the demonstration of high NKA activity in DO coexpressed with NKCC1 and CFTR indicates the presence of the conserved secondary active Cl- secretion mechanism found in other ion transporting epithelia suggesting a convergent evolution with other vertebrate salt secreting organs. However, the significant osmoregulatory challenge of HSW indicates that the DO may be of limited use under more extreme salinity conditions in contrast to the gill based ionoregulatory strategy of marine teleosts.

Effect of Short‐term Water Restriction on Blood Pressure Variability in Young Adults

Water restriction causes an acute decline in plasma volume and subsequently elevates serum sodium and plasma osmolality. Rodent models demonstrate that elevated serum sodium and plasma osmolality increases blood pressure (BP) variability. This is important because elevated BP variability is an independent risk factor for adverse cardiovascular events. However, the effects of water restriction on BP variability in humans remains to be determined.PURPOSETo test the hypothesis that short‐term water restriction increases serum sodium and plasma osmolality and leads to greater BP variability in humans.METHODSYoung healthy adults (13M/11F, age: 25±1 yrs; BMI: 24±1 kg/m2; BP 107±2/60±1 mmHg) completed two three‐day‐long hydration protocols in randomized order, separated by at least one week. Women were tested in the early follicular phase of their menstrual cycle. Daily water intake for euhydration (EU) was 23 mL H2O/kg/day. Water intake for hypohydration (HYPO) consisted of a stepwise daily reduction in water intake, followed by a 16‐hour water abstention period prior to testing. Laboratory testing was conducted on day four of the protocols. Participants wore an ambulatory BP monitor and collected urine for urinalysis for 24 hours preceding each study visit. The ambulatory BP monitoring provides BP variability under free‐living conditions. Upon arrival to the laboratory, participants rested quietly in a dimly lit room in the supine position for ten minutes for the assessment of beat‐to‐beat BP variability via finger photoplethysmography under controlled conditions. The average real variability (ARV) index, the average of the absolute differences between all consecutive BP measurements, was determined. Standard deviation (SD) of BP was also determined.RESULTSHYPO led to higher plasma osmolality (290.6±1.0 vs. 287.7±1.0 mOsm/kg H2O, p&lt;0.05), urine osmolality (707±42 vs. 470±32 mOsm/kg H2O, p&lt;0.05), urine specific gravity (1.023±0.001 vs. 1.016±0.006, p&lt;0.05) and thirst rating (7.0±0.4 vs. 2.7±0.6 on a 0–10 scale, p&lt;0.05) compared to EU. Plasma volume declined (−5.4±1.3%) during HYPO compared to EU. Daytime ambulatory systolic BP variability was not different between HYPO and EU (ARV BP 9.1±0.4 vs. 10.0±0.6; SD BP 10.3±0.8 vs. 12.4±1.1, p&gt;0.05 for both). Ambulatory mean and diastolic BP variability were not different between conditions (p&gt;0.05). Beat‐to‐beat systolic BP variability was not different between HYPO and EU (ARV BP 2.0±0.1 vs. 1.9±0.1; SD BP 5.4±0.4 vs. 5.0±0.3, p&gt;0.05 for both). Beat‐to‐beat mean and diastolic BP variability were also not different between conditions (p&gt;0.05).CONCLUSIONThese preliminary data suggest that short‐term water restriction in young healthy adults does not increase ambulatory or beat‐to‐beat BP variability.Support or Funding InformationSupported by NIH Grant 1R01HL128388This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Stress-related physiological changes and post-release survival of elephant fish (Callorhinchus milii) after longlining, gillnetting, angling and handling in a controlled setting

Stress-related physiological changes and post-release survival of elephant fish (Callorhinchus milii) in response to fishing capture and handling were assessed by experimental simulation using several different fishing gears for various periods under controlled laboratory conditions and by repeated blood sampling during a subsequent 72-h period to monitor the animals’ condition. Capture and handling caused physiological changes in elephant fish indicated by elevated plasma lactate, potassium and osmolality and immediately depressed plasma glucose. Maximum values of plasma potassium and osmolality occurred mainly immediately after capture (0 h), and maximum levels of plasma lactate at 0 and 3 h. Elevated plasma lactate concentrations returned to baseline values after 12 h of capture. Minimum levels of plasma glucose were recorded 3 h after capture. Hypoglycaemia followed by hyperglycaemia after stress was recorded. Handling alone significantly increased plasma lactate levels. Gillnet capture caused the greatest physiological stress, followed by longline, and then angling. Immediate mortality was 0% for all capture treatments, but delayed mortality varied widely among the capture treatments. Post-release survival rates were 70% (i.e. 30% delayed mortality) for longline and gillnet depending on fishing duration and 100% (i.e. 0% delayed mortality) for hook and line (angling) provided the animals were returned to the water immediately following capture. The best indicators of poor condition in this species were low plasma glucose concentration, red eyes (blood-shot), pale skin and impaired swimming.

The influence of acute elevations in plasma osmolality and serum sodium on sympathetic outflow and blood pressure responses to exercise.

Elevated plasma osmolality (pOsm) has been shown to increase resting sympathetic nerve activity in animals and humans. The present study tested the hypothesis that increases in pOsm and serum sodium (sNa+) concentration would exaggerate muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to handgrip (HG) exercise and postexercise ischemia (PEI). BP and MSNA were measured during HG followed by PEI before and after a 23-min hypertonic saline infusion (HSI-3% NaCl). Eighteen participants (age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed the protocol; pOsm and sNa+ increased from pre- to post-HSI (285 ± 1 to 291 ± 1 mosmol/kg H2O; 138.2 ± 0.3 to 141.3 ± 0.4 mM; P < 0.05 for both). Resting mean BP (90 ± 2 vs. 92 ± 1 mmHg) and MSNA (11 ± 2 vs. 15 ± 2 bursts/min) were increased pre- to post-HSI ( P < 0.05 for both). Mean BP responses to HG (106 ± 2 vs. 111 ± 2 mmHg, P < 0.05) and PEI (102 ± 2 vs. 107 ± 2 mmHg, P < 0.05) were higher post-HSI. Similarly, MSNA during HG (20 ± 2 vs. 29 ± 2 bursts/min, P < 0.05) and PEI (19 ± 2 vs. 24 ± 3 bursts/min, P < 0.05) were greater post-HSI. In addition, the change in MSNA was greater post-HSI during HG (Δ9 ± 2 vs. Δ13 ± 3 bursts/min, P < 0.05). A second set of participants ( n = 13, age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed a time control (TC) protocol consisting of quiet rest instead of an infusion. The TC condition yielded no change in resting sNa+, pOsm, mean BP, or MSNA (all P > 0.05); responses to HG and PEI were not different pre- to post-quiet rest ( P > 0.05). In summary, acutely increasing pOsm and sNa+ exaggerates BP and MSNA responses during HG exercise and PEI. NEW & NOTEWORTHY Elevated plasma osmolality has been shown to increase resting sympathetic activity and blood pressure. This study provides evidence that acute elevations in plasma osmolality and serum sodium exaggerated muscle sympathetic nerve activity and blood pressure responses during exercise pressor reflex activation in healthy young adults.

Reduced water intake deteriorates glucose regulation in patients with type 2 diabetes

Epidemiological research has demonstrated that low daily total water intake is associated with increased diagnosis of hyperglycemia. Possible mechanisms for this increase include hormones related to the hypothalamic pituitary axis as well as the renin-angiotensin-aldosterone system (RAAS). Therefore, the hypothesis of the present study was that acute low water intake would result in differential hormonal profiles and thus impaired blood glucose regulation during an oral glucose tolerance test (OGTT) in people with type 2 diabetes mellitus (T2DM). Nine men (53 ± 9 years, 30.0 ± 4.3 m∙kg−2, 32% ± 6% body fat) diagnosed with T2DM completed OGTTs in euhydrated (EUH) and hypohydrated (HYP) states in counterbalanced order. Water restriction led to hypohydration of −1.6% of body weight, with elevated plasma (EUH: 288 ± 4, HYP: 298 ± 6 mOsm·kg−1; P < .05) and urine (EUH: 512 ± 185, HYP: 994 ± 415 mOsm·kg−1; P < .05) osmolality. There was a significant main effect of condition for serum glucose (at time 0 minute 9.5 ± 4.2 vs 10.4 ± 4.4 mmol∙L−1 and at time 120 minutes 19.1 ± 4.8 vs 21.0 ± 4.1 mmol∙L−1 for EUH and HYP, respectively; P < .001) but not insulin (mean difference between EUH and HYP −12.1 ± 44.9 pmol∙L−1, P = .390). An interaction between time and condition was observed for cortisol: decrease from minute 0 to 120 in EUH (−85.3 ± 82.1 nmol∙L−1) vs HYP (−25.0 ± 43.0 nmol∙L−1; P = .017). No differences between conditions were found within RAAS-related hormones. Therefore, we can conclude that 3 days of low total water intake in people with T2DM acutely impairs blood glucose response during an OGTT via cortisol but not RAAS-mediated glucose regulation.

Similarity of osmoregulatory capacity in coastal and inland alligator gar

The alligator gar Atractosteus spatula is a primitive fish species, occupying a wide range of temperature and salinity habitats. Long-distance movements are limited, leading to genetic differentiation between inland and coastal populations. Unknown is whether physiological capacity differs between geographically separated populations, particularly for traits important to osmoregulation in saline environments. Alligator gar from inland and coastal populations were reared in a similar environment and exposed to temperature (10, 30°C) and salinity (0, 20ppt) extremes to determine whether iono- and osmoregulatory ability differed between populations. There were few differences in osmoregulatory ability between populations, with similar gill, blood and gastrointestinal tract osmoregulatory parameters. Blood plasma osmolality, ion concentrations, intestinal pH and bicarbonate base concentrations, intestinal fluid osmolality, ion concentrations and gill Na+, K+-ATPase (NKA) activity were similar between populations. Notably, gar from both populations did not osmoregulate well at low temperature and high salinity, with elevated plasma osmolality and ion concentrations, low gill NKA, and little evidence of gastrointestinal tract contribution to ionic and base regulation based on a lack of intestinal fluid and low base content. Therefore, the hypothesis that coastal gar would have improved osmotic regulatory ability in saline environments as compared to inland alligator gar was not supported, suggesting physiological capacity may be retained in primitive species possibly due to its importance to their persistence through time.

Mild dehydration modifies the cerebrovascular response to the cold pressor test.

The cold pressor test (CPT) is widely used in clinical practice and physiological research. It is characterized by a robust autonomic response, with associated increases in heart rate (HR), mean arterial pressure (MAP) and mean middle cerebral artery blood flow velocity (MCAv(mean)). Hydration status is not commonly reported when conducting this test, yet blood viscosity alone can modulate MCAv(mean), potentially modifying the MCAv(mean) response to the CPT. We investigated the effect of mild dehydration on the physiological response to the CPT in 10 healthy men (mean ± SD: age 28 ± 5 years; body mass 83 ± 5 kg). All participants completed two CPTs, cold water (0°C) immersion of both feet for 90 s, with the order of the euhydration and dehydration trials counterbalanced. Beat-to-beat MCAv, MAP, HR and breath-by-breath partial pressure of end-tidal CO2 (P(ET,CO2)) were measured continuously. Participants' pain perception was measured 1 min into the CPT using a visual analog scale (no pain = 0; maximal pain = 10). Dehydration significantly elevated plasma osmolality and urine specific gravity and reduced body mass (all P < 0.01). The MAP and HR responses were not different between treatments (both P > 0.05). After 90 s of immersion, the change in MCAv(mean) from baseline was less in the dehydration compared with the euhydration trial (change 0 ± 5 versus 7 ± 7 cm s(-1), P = 0.01), as was P(ET,CO2) (change -3 ± 2 versus 0 ± 3 mmHg, P = 0.02). Dehydration was associated with greater relative pain sensation during the CPT (7.0 ± 1.3 vs 5.8 ± 1.8, P = 0.02). Our results demonstrate that mild dehydration can modify the cerebrovascular response to the CPT, with dehydration increasing perceived pain, lowering P ET ,CO2 and, ultimately, blunting the MCAv(mean) response.

Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.

Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.

PO-0059 Central Diabetes Insipidus In Children: Clinical Profile And Etiologies Monocentric Experience (about 10 Cases)

Introduction Central diabetes insipidus (CDI) or neurohypophyseal diabetes insipidus is a rare disorder in children caused by an inadequate release of the antidiuretic hormone, arginine vasopressin (AVP). CDI is clinically caracterised by polyuria and polydipsia. Methods and materials Clinical, auxological, biological and neuroradiological characteristics of 10 children with central diabetes insipidus (CDI) were retrospectively analysed during a period of 18 years. Results Five girls and five boys with permanent diabetes insipidus were enrolled in the study. The mean age at diagnosis was 6 years five months (range: 4 months -14 years). The major cumulative and often subtle presenting manifestations were: polyuria (n = 10), polydipsia (n = 10), fatigue (n = 2), growth retardation (n = 4), headache (n = 1). All patients had low urine osmolality and elevated plasma osmolality on diagnosis. The aetiology of central DI was organic in 8 patients, craniopharyngioma in 3 patients, Langerhans cell histiocytosis in 2 patients, neurosarcoidosis in one case, Pituitary stalk interruption in one patient and wolfram syndrome in one patient. Three patients had anterior pituitary hormone deficiency and growth hormone deficiency. Polyuria and polydipsia have regressed in all patients put under desmopressin. Patients with craniopharyngioma were operated with a tumour recurrence in one case. Conclusion DIC is a rare disease in Paediatrics. The circumstances of discovery and positive diagnosis are often easy. The underlying aetiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Clinical characteristics of central diabetes insipidus in Taiwanese children

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Hyperglycemic Emergencies in Adults

Hyperglycemic Emergencies in Adults