Elevated Sodium Levels Research Articles

Evaluation of anti-urolithiatic and diuretic activities of watermelon (Citrullus lanatus) using in vivo and in vitro experiments

Traditionally, Citrullus lanatus is known to have protective properties in kidney diseases and for having the ability to clear urine. Current study aims to validate the traditional uses of C. lanatus by evaluation of anti-urolithiatic and diuretic activities using in vivo and in vitro experiments. Male Wistar rats were used for in vivo anti-urolithiatic and diuretic activities. Supersaturated solution of calcium and oxalate was used for in vitro crystallization study. Hematoxylin & eosin staining was used for histopathological evaluation of kidney. In the in vivo rat model of urolithiasis, the pulp extract reduced calcium oxalate (CaOX) crystal count in both kidney and urine. The pulp extract also increased the urinary pH and output, and prevented the weight loss. Serum analysis showed elevation in creatinine clearance and reduction in urea and creatinine levels. Urinary analysis demonstrated that pulp extract restored altered phosphate, calcium, oxalate, and citrate levels. In the in vivo rat model of diuresis; the pulp extract produced diuresis, reduced serum chloride levels, and elevated urinary sodium and chloride levels. In the in vitro crystallization experiment, pulp extract inhibited the aggregation phase. Seed extract failed to show any convincing results. GC–MS analysis revealed the presence of steroids and alkanes as the major constituents of pulp extract, which might be responsible for anti-urolithiatic activity; however, further studies are required for isolation and identification of active constituents. Current study validated the traditional uses of watermelon and demonstrated that pulp extract possessed significant anti-urolithiatic and diuretic activities.

Microcirculatory parameters in compensated and decompensated type 2 diabetes mellitus

To reveal the features of microcirculatory parameters in compensated and decompensated type 2 diabetes mellitus (T2DM). A total of 196 patients with T2DM were examined and divided into 2 groups: 1) 52 patients (40.4% of men) aged 52.8±8.7 years with compensated T2DM (glycated hemoglobin (HbA1с), 6.3±0.5%); 2) 68 patients (38.2% of men) aged 52.8±8.1 years with decompensated T2DM (HbA1с, 9.4±1.7%). Both patient groups had concomitant hypertension (its prevalence, degree, stage of hypertension were comparable). A control group consisted of 76 volunteers (40.8% of men) aged 52.2±8.7 years with normal carbohydrate metabolism and without signs of cardiovascular disease (HbA1с, 5.3±0.49%). Capillary blood flow in the finger nail-fold area was investigated in all the participants. A digital optical capillaroscope with image-processing software was used to obtain quantitative blood microcirculatory parameters. The diameters of arterial and venous capillary segments were measured, by calculating the remodeling rate. The degree of capillary tortuosity, network density, and polymorphism and the size of the perivascular zone (PZ) were estimated. Blood rheological properties and capillary blood flow velocity were also investigated. The decompensated T2DM group compared to the compensated T2DM group was found to have a narrowing of the arterial capillary segment diameter (8.4±2.0 µm; p=0.009) and an increase in remodeling rates (1.47±0.22; p=0.000). The tendency of the PZ size to be larger in patients with decompensated T2DM compared to those with compensated T2DM (p=0.080) and the increase in this indicator compared to the control group (p=0.001) reflect the presence of edema syndrome in Group 2, as laboratory confirmed by a statistically significantly elevated sodium level (p=0.000; p=0.006). The enlarged venous capillary segment demonstrates involvement of the venous component in microcirculatory disorders in T2DM. The reduction in the density of the capillary network and the increase in capillary tortuosity and polymorphism, which were also observed in the patients of both groups versus the control group, are referred to as disorders that are characteristic of T2DM. In decompensated T2DM, capillary bed structural and functional changes are found as a narrowing of the arterial capillary segment, an increase in the rate of remodeling, and enlargement of the PZ. Digital capillaroscopy opens up new possibilities for assessing the magnitude of changes in the microcirculatory system in DM and can simultaneously evaluate the efficiency of treatment, by monitoring the status of the microvasculature.

Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization

Avascular necrosis of the femur head (AVNFH) is a debilitating disease caused due to the use of alcohol, steroids, following trauma or unclear (idiopathic) etiology, affecting mostly the middle aged population. Clinically AVNFH is associated with impaired blood supply to the femoral head resulting in bone necrosis and collapse. Although Homocysteine (HC) has been implicated in AVNFH, levels of homocysteine and its associated pathway metabolites have not been characterized. We demonstrate elevated levels of homocysteine and concomitantly reduced levels of vitamins B6 and B12, in plasma of AVNFH patients. AVNFH patients also had elevated blood levels of sodium and creatinine, and reduced levels of random glucose and haemoglobin. Biophysical and ultrastructural analysis of AVNFH bone revealed increased remodelling and reduced bone mineral density portrayed by increased carbonate to phosphate ratio and decreased Phosphate to amide ratio together with disrupted trabeculae, loss of osteocytes, presence of calcified marrow, and elevated expression of osteocalcin in the osteoblasts localized in necrotic regions. Taken together, our studies for the first time characterize the metabolomic, pathophysiological and morphometric changes associated with AVNFH providing insights for development of new markers and therapeutic strategies for this debilitating disorder.

Effects of Tolvaptan in patients with acute heart failure: a systematic review and meta-analysis

BackgroundAcute heart failure, which requires urgent evaluation and treatment, is a leading cause for admission to the emergency department. The aim of this meta-analysis was to evaluate the effects of tolvaptan on acute heart failure and compare them with the effects of conventional therapy or placebo.MethodsThe electronic databases PubMed, EMBASE, and the Cochrane Controlled Trial registry were searched from their starting dates to October 24, 2016. Two authors independently read the trials and extracted related information from the included studies. We used fixed-effects or random-effects models to assess the overall combined risk estimates according to I2 statistics. Analysis to determine sensitivity and publication bias was conducted.ResultsSix randomised controlled trials from eight articles, with a total of 746 patients, were included for analysis. Compared with the control, tolvaptan reduced body weight in two days (WMD 1.35; 95% CI 0.75 to 1.96), elevated sodium level in two days (WMD 2.33; 95% CI 1.08 to 3.57) and five days (WMD 1.57; 95% CI 0.04 to 3.09), and ameliorated symptoms of dyspnoea (RR 0.82; 95% CI 0.71–0.95). However, tolvaptan did not improve long-term (RR 1.04; 95% CI 0.66–1.62) or short-term all-cause mortality (RR 0.89; 95% CI 0.45–1.76), incidence of clinical events (worsening heart failure, RR 0.75; 95% CI 0.50–1.12 and worsening renal function, RR 0.97; 95% CI 0.75–1.27), and length of hospital stay in patients (WMD 0.14; 95% CI -0.29 to 2.38) with acute heart failure.ConclusionTolvaptan can decrease body weight, increase serum sodium level, and ameliorate some of the congestion symptoms in patients with acute heart failure, which may help avoid the overdose of loop diuretics, especially in patients with renal dysfunction.

Salt-induced Na+/K+-ATPase-α/β expression involves soluble adenylyl cyclase in endothelial cells.

High dietary salt intake may lead to vascular stiffness, which predicts cardiovascular diseases such as heart failure, and myocardial and cerebral infarctions as well as renal impairment. The vascular endothelium is a primary target for deleterious salt effects leading to dysfunction and endothelial stiffness. We hypothesize that the Ca2+- and bicarbonate-activated soluble adenylyl cyclase (sAC) contributes to Na+/K+-ATPase expression regulation in vascular endothelial cells and is an important regulator of endothelial stiffness. In vitro stimulation of vascular endothelial cells with high sodium (150mM Na+)-induced Na+/K+-ATPase-α and Na+/K+-ATPase-β protein expression determined by western blot. Promoter analyses revealed increased cAMP response element (CRE)-mediated Na+/K+-ATPase-α transcriptional activity under high sodium concentrations. Inhibition of sAC by the specific inhibitor KH7 or siRNA reduced the sodium effects. Flame photometry revealed increased intracellular sodium concentrations in response to high sodium stimulations, which were paralleled by elevated ATP levels. Using atomic force microscopy, a nano-technique that measures cellular stiffness and deformability, we detected significant endothelial stiffening under increased sodium concentrations, which was prevented by inhibition of sAC using KH7 and Na+/K+-ATPase using ouabain. Furthermore, analysis of primary aortic endothelial cells in an in vitro aging model revealed an impaired Na+/K+-ATPase-α sodium response and elevated intracellular sodium levels with cellular aging. We conclude that sAC mediates sodium-induced Na+/K+-ATPase expression in vascular endothelium and is an important regulator of endothelial stiffness. The reactivity of Na+/K+-ATPase-α expression regulation in response to high sodium seems to be impaired in aging endothelial cells and might be a component of endothelial dysfunction.

Coal-Bed Methane Water: Effects on Soil Properties and Camelina Productivity.

Every year, the production of coal-bed natural gas in the Powder River Basin results in the discharge of large amounts of coal-bed methane water (CBMW) in Wyoming; however, no sustainable disposal methods for CBMW are currently available. A greenhouse study was conducted to evaluate the potential to use CBMW as a source of irrigation water for camelina [ (L.) Crantz]. We assessed the effects of three CBMW concentrations (0% [1:0], 50% [1:1], and 100% [0:1] tap water to CBMW) on selected soil properties, growth, seed oil, and fatty acid composition of three camelina cultivars: Blaine Creek, Ligena, and Pronghorn. The 100% CBMW reduced seed and estimated biofuel yields by 24 and 23%, respectively, but increased the oil content by 3%, relative to the control. Additionally, the 100% CBMW visibly affected soil through formation of surface crust due to elevated levels of sodium (653 mg Na kg). The 50% CBMW had no significant effects on the seed yield, estimated biofuel yield, and oil content, but the soil Na levels were still high (464 mg kg), which could pose a long-term impact on soil structure. The CBMW tended to reduce the total saturated fatty acid, but it had no significant effects on the total monounsaturated or polyunsaturated fatty acids of camelina seeds. Overall, CBMW diluted with an equal amount of good-quality water could be used to irrigate camelina in the short term. Afterward, only good-quality water would have to be used until the accumulated dissolved solids are flushed out.

Contamination of soils with Cu, Na and Hg due to the highway and railway transport

Contamination of soils with three metals due to the highway and railway transport was studied. Copper was selected as a suitable indicator for both kinds of transportation. Sodium served to assess the level of contamination resulting from the road salting in winter. Mercury was determined in samples taken close to the railway in order to test its release from impregnated wooden ties. All analyses were determined using the methods of the trace element analysis; values are expressed as dry matter. The highest concentrations of copper, sodium and total mercury in soil samples were 52.7 mg/kg, 770 mg/kg and 0.181 mg/kg respectively. The highest copper content was observed in soils taken close to the railroad and the highway. Elevated sodium levels originated from winter road salting – the highest winter value was 770 mg/kg as compared with maximal summer value of 416 mg/kg. The concentration of total mercury in soils depended on the type of railway ties used – the highest values for location with wooden and concrete ties were 0.181 mg/kg and 0.145 mg/kg, respectively. Wooden railroad ties are considered as a potential source of mercury because of impregnation with antifungal mercury compounds.

Do high-salt microenvironments drive hypertensive inflammation?

Hypertension is a global epidemic affecting over one billion people worldwide. Despite this, the etiology of most cases of human hypertension remains obscure, and treatment remains suboptimal. Excessive dietary salt and inflammation are known contributors to the pathogenesis of this disease. Recently, it has been recognized that salt can accumulate in the skin and skeletal muscle, producing concentrations of sodium greater than the plasma in hypertensive animals and humans. Such elevated levels of sodium have been shown to alter immune cell function. Here, we propose a model in which tissue salt accumulation causes an immune response leading to renal and vascular inflammation and hypertension.

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model. RESULTS: A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality. CONCLUSION: Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set.

Women with a Common Genetic Variant in ZnT2 (T288S) Have Altered Breast Milk Composition: Implications for Suboptimal Lactation

Few studies have explored the role of nutrigenomics in lactation biology. Recent studies from our lab found that non‐synonymous genetic variation in the zinc (Zn) transporter ZnT2 (SLC30A2) is common in women and is associated with both low and elevated milk Zn concentrations. Of those variants, a threonine to serine substitution at amino acid 288 (T288S) was detected in 12% of women and milk from these women had abnormally low milk Zn and significantly elevated milk sodium levels. Because elevated milk sodium has been associated with breast dysfunction, in this study, we characterized the functional consequence of expressing the T288S variant on breast milk composition in women and in mammary epithelial cells (MECs) ectopically expressing this variant in vitro. We hypothesized that mothers with T288S variant would express biological factors in milk that reflect suboptimal lactation performance. We found that protein, lactose and fat concentrations in milk from women with T288S were similar to women expressing wild‐type ZnT2. However, milk from women expressing T288S had significantly higher levels of citrate, lactoferrin, MMP‐2 activity, 4‐HNE, mucin‐4 and endoplasmin, all of which increase in response to reactive oxygen species (ROS). Consistent with the milk analyses, MECs transfected to express T288S in vitro had significantly greater ROS levels and expression of oxidative stress markers, mucin‐4 and endoplasmin, compared to MECs expressing wild‐type ZnT2. To determine if this increase in oxidative stress is associated with mammary gland involution, we measured p‐STAT3, a marker of involution and found that STAT3 activation was significantly increased in T288S‐expressing MECs compared to MECs expressing wild‐type ZnT2. Collectively, our data suggest that women expressing the T288S variant in ZnT2 may have enhanced oxidative stress in the breast that may lead to precocious involution and suboptimal lactation. Importantly, this study suggests that nutrigenomics may have important implications for breast function and implicates factors in breast milk as useful bioreporters of breast (dys)function and lactation performance.Support or Funding InformationIntramural funds to SLK

Hypernatremia at Hospital Discharge and Out of Hospital Mortality Following Primary Intracerebral Hemorrhage.

In patients with intracerebral hemorrhage (ICH), it is not clear if hypernatremia is merely a marker of disease severity or if elevated sodium levels are harmful. We hypothesized that hypernatremia at hospital discharge in primary ICH patients would be associated with increased mortality following discharge. We performed a two-center observational study of critically ill ICH patients in Boston. We studied 5100 patients, age ≥18years, who were diagnosed with ICH (ICD-9 code 431), received medical or surgical critical care between 1997 and 2011 and survived hospitalization. The exposure of interest was serum sodium within 24h of hospital discharge, categorized as Na≤145mmol/L and Na>145mmol/L. The primary outcome was 30-day post-discharge mortality. Odds ratios were estimated by logistic regression models adjusted for age, race, gender, Deyo-Charlson Index, patient type (medical versus surgical) and sepsis. In ICH patients who received critical care and survived hospitalization, the serum sodium at discharge was a predictor of post-discharge mortality. Patients with a discharge Na>145mmol/L have an OR for mortality in the 30days following hospital discharge of 1.82 (95%CI 1.38-2.38; P<0.001) and an adjusted OR of 1.87 (95%CI 1.40-2.48; P<0.001) both relative to patients with a discharge Na≤145mmol/L. The adjusted model showed good discrimination AUC 0.77 (95%CI 0.74-0.79) and calibration (Hosmer-Lemeshow χ (2) P=0.68). In critically ill ICH patients who survive hospitalization, hypernatremia at the time of discharge is a robust predictor of post-discharge mortality.

Ionic imbalance, in addition to molecular crowding, abates cytoskeletal dynamics and vesicle motility during hypertonic stress

Cell volume homeostasis is vital for the maintenance of optimal protein density and cellular function. Numerous mammalian cell types are routinely exposed to acute hypertonic challenge and shrink. Molecular crowding modifies biochemical reaction rates and decreases macromolecule diffusion. Cell volume is restored rapidly by ion influx but at the expense of elevated intracellular sodium and chloride levels that persist long after challenge. Although recent studies have highlighted the role of molecular crowding on the effects of hypertonicity, the effects of ionic imbalance on cellular trafficking dynamics in living cells are largely unexplored. By tracking distinct fluorescently labeled endosome/vesicle populations by live-cell imaging, we show that vesicle motility is reduced dramatically in a variety of cell types at the onset of hypertonic challenge. Live-cell imaging of actin and tubulin revealed similar arrested microfilament motility upon challenge. Vesicle motility recovered long after cell volume, a process that required functional regulatory volume increase and was accelerated by a return of extracellular osmolality to isosmotic levels. This delay suggests that, although volume-induced molecular crowding contributes to trafficking defects, it alone cannot explain the observed effects. Using fluorescent indicators and FRET-based probes, we found that intracellular ATP abundance and mitochondrial potential were reduced by hypertonicity and recovered after longer periods of time. Similar to the effects of osmotic challenge, isovolumetric elevation of intracellular chloride concentration by ionophores transiently decreased ATP production by mitochondria and abated microfilament and vesicle motility. These data illustrate how perturbed ionic balance, in addition to molecular crowding, affects membrane trafficking.

Predictors of non-transplantation of adult donor organs--an observational study using routine data from Eurotransplant.

BackgroundThe majority of pancreases, offered in allocation, are not transplanted. This pancreas under-utilisation is a phenomenon observed in all transplant systems in North-America and Europe. It was the aim of this study to analyse factors predictive of pancreas non-transplantation in Germany.MethodsRoutine Eurotransplant data of 3,666 deceased German donors (from 2002–2011) were used for multivariate modelling. Socio-demographic and medical factors were considered as independent variables in logistic regression models with non-transplantation as dependent variable.ResultsMale gender, advanced age, overweight/obesity, long ICU stay, a history of smoking, non-traumatic brain death, elevated levels of sodium, serum glucose, lipase/amylase and the liver not being considered for procurement were significant independent predictors of non-transplantation.ConclusionIn line with previous research, advanced age, high BMI, long ICU stay and the liver not being considered for procurement were the strongest predictors of pancreas non-transplantation in Germany. About three quarters of the variance remained unexplained, suggesting that factors not assessed or unknown may play a decisive role.

Intracarotid hypertonic sodium chloride differentially modulates sympathetic nerve activity to the heart and kidney

Hypertonic NaCl infused into the carotid arteries increases mean arterial pressure (MAP) and changes sympathetic nerve activity (SNA) via cerebral mechanisms. We hypothesized that elevated sodium levels in the blood supply to the brain would induce differential responses in renal and cardiac SNA via sensors located outside the blood-brain barrier. To investigate this hypothesis, we measured renal and cardiac SNA simultaneously in conscious sheep during intracarotid infusions of NaCl (1.2 M), sorbitol (2.4 M), or urea (2.4 M) at 1 ml/min for 4 min into each carotid. Intracarotid NaCl significantly increased MAP (91 ± 2 to 97 ± 3 mmHg, P < 0.05) without changing heart rate (HR). Intracarotid NaCl was associated with no change in cardiac SNA (11 ± 5.0%), but a significant inhibition of renal SNA (-32.5 ± 6.4%, P < 0.05). Neither intracarotid sorbitol nor urea changed MAP, HR, central venous pressure, cardiac SNA, and renal SNA. The changes in MAP and renal SNA were completely abolished by microinjection of the GABA agonist muscimol (5 mM, 500 nl each side) into the paraventricular nucleus of the hypothalamus (PVN). Infusion of intracarotid NaCl for 20 min stimulated a larger increase in water intake (1,100 ± 75 ml) than intracarotid sorbitol (683 ± 125 ml) or intracarotid urea (0 ml). These results demonstrate that acute increases in blood sodium levels cause a decrease in renal SNA, but no change in cardiac SNA in conscious sheep. These effects are mediated by cerebral sensors located outside the blood-brain barrier that are more responsive to changes in sodium concentration than osmolality. The renal sympathoinhibitory effects of sodium are mediated via a pathway that synapses in the PVN.

The pathological features of Wernicke encephalopathy

Case reportA 47-year-old man with a history of alcoholic liver diseasewas found dead at his home address on the floor, lying facedown. He had been unwell for 2 months prior to death andhad complained of abdominal pain. He also had a diagnosisof prolonged QT interval.At autopsy there was no evidence of liver failurealthough the liver was fatty and fibrotic. There was acongenital anomaly of the coronary arteries with the cir-cumflex coronary artery arising from the right sinus ofValsalva with significant narrowing of the ostium. Therewas no evidence of trauma and toxicological screening ofblood was unremarkable. Biochemical analysis of vitreoushumor revealed elevated sodium (144 mmol/L) and creat-inine (217 lmol/L) levels in keeping with terminal dehy-dration and renal failure, with a normal b-hydroxy butyrate(thus excluding alcoholic ketoacidosis).Althoughthebrainappearedexternallyunremarkablewithnovermal atrophy of the cerebellum, sectioning of the mammillarybodiesdemonstratedsymmetricalhemorrhagehighlysuggestiveof Wernicke encephalopathy (Figs. 1, 2). Focal hemorrhagicareas were also noted within the walls of the third ventricle.Microscopically the mammillary bodies displayedrecent microhemorrhages and prominent microvascularproliferation with endothelial swelling typical of Wernickeencephalopathy (Fig. 3). The mammillothalamic tracts andthe walls of third ventricle also contained microhemor-rhages. There was patchy microvacuolation of the neuropilwith unremarkable neurons, fibrous astrocytes, and occa-sional perivascular macrophages containing hemosiderin,indicative of more chronic disease. Mild extravasation oferythrocytes and prominent congested vessels were notedwithin medullary dorsal motor vagal nuclei.Death was attributed to natural causes, most likelyinvolving a combination of cardiac and alcohol-relateddisease. The striking finding was of clinically unsuspectedWernicke encephalopathy.DiscussionWernicke encephalopathy is a neurological disorderresulting from thiamine (vitamin B-1) deficiency [1].Although in Western countries it occurs predominantly inalcoholics, related to poor dietary intake and impairedutilization, it can also be caused by a variety of otherconditions that interfere with normal thiamine metabolism.These include starvation, bariatric surgery, hyperemesisgravidarum, human immunodeficiency virus/acquiredimmunodeficiency syndrome (HIV/AIDS), and in infantsgiven thiamine-deficient formulas [1, 2].The clinical prevalence of Wernicke encephalopathy isuncertain as autopsy studies indicate that the condition islikely under-diagnosed during life [3]. Delay in diagnosismay result from nonspecific symptoms that resembleintoxication. The symptoms, severity, and the regions ofthe brain that are affected are also variable due to a

Hair trace elementary profiles in aging rodents and primates: links to altered cell homeodynamics and disease

Aging is associated with an increased incidence of pathological conditions such as neurodegeneration, cardiovascular and renal disease, and cancer. These conditions are believed to be linked to a disruption in cell homeodynamics, which is regulated by essential trace elements. In this study we used hair elementary analysis by inductively coupled plasma mass spectrometry (ICPMS) to examine age-related profiles of 47 elements in both rats and common marmoset monkeys. Hair was collected from young adult (6months) and aged (18months) Long-Evans male rats, and young adult (2years), middle-aged (4years) and aged (>8years) marmosets. The results revealed that aging reduces content levels of cobalt, potassium and seleniumwhile content levels of aluminium, arsenic, boron, mercury, molybdenum, and titanium were elevated in aged rats. Similarly, aged marmosets showed reduced levels of cobalt and elevated levels of aluminium. Case studies in aged rats revealed that myocardial infarction was associated with elevated levels of sodium, potassium and cadmium and reduced zinc, while renal failure was linked to elevated content of potassium, chloride and boron and reduced contents of manganese. Carcinoma was linked to elevated arsenic and reduced selenium levels. These findings indicate that hair elementary profiles in healthy aging and age-related diseases reflect altered cell and organ metabolic functions. Cobalt and aluminium in particular may serve as biomarkers of aging in animal models. Thus, elementary deposition in hair may have predictive and diagnostic value in age-related pathological conditions, including cardiovascular and kidney disease and cancer.

Electrolytes levels in asthmatic patients

Background: abnormal electrolytes concentrations in asthma patients can be attributed to low intake or secondary to asthma medications. Objectives: to identify the pattern of changes in electrolytes concentrations among asthmatic patients and to detect correlations between concentrations of electrolytes and pulmonary function measurements. Materials and Methods: the study involved a control group of 56 nonasthmatic subjects matched for gender and age with a study group of 100 patients with a medical history of asthma but no other respiratory diseases. IQ TQ Spirometer was used to assess pulmonary function according to ATS/ERS standards. Sodium, potassium, calcium and magnesium concentrations were measured from venous blood samples. Results: There were significant positive correlations between potassium concentration and FEV1, FEF50%, FEF25-75% (P 0.05). Conclusion: sodium and magnesium concentrations of asthmatic patients showed no significant differences in the means when compared with the control group, but elevated levels of sodium were associated with poor ventilatory function. High levels of potassium were associated with better pulmonary ventilation.

Transient reversal of the sodium/calcium exchanger boosts presynaptic calcium and synaptic transmission at a cerebellar synapse

The sodium/calcium exchanger (NCX) is a widespread transporter that exchanges sodium and calcium ions across excitable membranes. Normally, NCX mainly operates in its "forward" mode, harnessing the electrochemical gradient of sodium ions to expel calcium. During membrane depolarization or elevated internal sodium levels, NCX can instead switch the direction of net flux to expel sodium and allow calcium entry. Such "reverse"-mode NCX operation is frequently implicated during pathological or artificially extended periods of depolarization, not during normal activity. We have used fast calcium imaging, mathematical simulation, and whole cell electrophysiology to study the role of NCX at the parallel fiber-to-Purkinje neuron synapse in the mouse cerebellum. We show that nontraditional, reverse-mode NCX activity boosts the amplitude and duration of parallel fiber calcium transients during short bursts of high-frequency action potentials typical of their behavior in vivo. Simulations, supported by experimental manipulations, showed that accumulation of intracellular sodium drove NCX into reverse mode. This mechanism fueled additional calcium influx into the parallel fibers that promoted synaptic transmission to Purkinje neurons for up to 400 ms after the burst. Thus we provide the first functional demonstration of transient and fast NCX-mediated calcium entry at a major central synapse. This unexpected contribution from reverse-mode NCX appears critical for shaping presynaptic calcium dynamics and transiently boosting synaptic transmission, and is likely to optimize the accuracy of cerebellar information transfer.

Falsely Elevated Sodium Levels During Thiopental Treatment in the ICU: Technical Interference on a Laboratory Device with Important Clinical Relevance

Thiopental is a cornerstone in the treatment of refractory status epilepticus and intractable intracranial hypertension. In our center we observed that thiopental might cause falsely elevated serum sodium levels. Triggered by a recent case experience of extremely elevated serum sodium levels during thiopental treatment, we retrospectively identified 53 patients treated with thiopental in our intensive care unit between 2007 and 2011 and evaluated electrolyte changes. We differentiated the analysis before and after introduction of a new device for sodium assays (Dimension Vista, Siemens) in the central laboratory in April 2010. Standardized in vitro laboratory tests were performed to study the effect of thiopental on sodium analysis. Before April 2010, serum sodium levels determined in the central laboratory showed a good agreement with the bedside point-of-care (POC) device during thiopental therapy with [sodium](laboratory) - [sodium](POC) of only 1.08 mmol/L (P = .0517). After April 2010, a strong discrepancy between laboratory values and POC values was observed with [sodium](laboratory) - [sodium](POC) = 11.57 mmol/L (P < .0001). Standardized in vitro testing confirmed that thiopental induced a dose-dependent false hypernatremia (P = .002). Thiopental treatment can result in falsely elevated serum sodium. This is a critical finding since high sodium levels preclude administrating mannitol or hypertonic saline for the treatment of elevated intracranial pressure. Moreover, a false high sodium level might lead to the inappropriate administration of hypotonic fluids potentially resulting in increased brain edema and even higher intracranial pressure. To our knowledge, this is the first paper describing this clinically relevant phenomenon.

Is the Habitation of Acidic-Water Sanctuaries by Galaxiid Fish Facilitated by Natural Organic Matter Modification of Sodium Metabolism?

Acidic waters of New Zealand's West Coast are hypothesized to be a refuge for native galaxiid fish, allowing them to escape predation from acid-sensitive invasive salmonid species. To determine the mechanisms by which galaxiids tolerate low pH, we investigated sodium metabolism in inanga Galaxias maculatus in response to water pH, short-term acclimation to acidic waters, the presence and source of natural organic matter (NOM), and fish life history. Contrary to expectation, inanga were physiologically sensitive to acid exposure, displaying inhibited sodium influx and exacerbated sodium efflux. Short-term (144 h) acclimation to acid did not modify this effect, and NOM did not exert a protective effect on sodium metabolism at low pH. Inanga sourced from naturally acidic West Coast waters did, however, display a sodium influx capacity (J(max)) that was significantly elevated when compared with that of fish collected from neutral waters. All inanga, independent of source, exhibited exceptionally high sodium uptake affinities (18-40 μM) relative to previously studied freshwater teleosts. Although inanga displayed relatively poor physiological tolerance to acidic waters, their high sodium influx affinity coupled with their occupation of near-coastal waters with elevated sodium levels may permit habitation of low-pH freshwaters.