Impact of chronic potassium binder treatment on the clinical outcomes in patients with hyperkalemia: Results of a nationwide hospital-based cohort study.

Introduction: Hyperkalemia (HK) is a common disorder in patients with heart failure or chronic kidney disease, and potassium binders (PBs) are recommended to control serum potassium (S-K) levels. Although HK is often a chronic condition, short-term and intermittent PBs treatment has been largely applied to control S-K levels, and little is known about the impact of long-term and chronic PBs treatment on clinical outcomes. Method: This retrospective cohort study was conducted using a Japanese claims database (April 2008-September 2018). HK was defined as at least two S-K ≥5.1 mmol/L within a 12-month(M) interval. The index date was defined as the initial PB prescription date, and the S-K values were examined at 3M, 6M, and 12M after the index. The medication possession ratio (MPR) was used to evaluate the length of the prescribed period of PB, as prescription refill was not allowed in Japan. Clinical outcomes were analyzed by comparing MPR <80% to MPR ≥80% using Cox proportional hazards regression. Results: We found 4,321 patients with HK and were on initial PB treatments, and 993 and 3,328 patients were categorized in the MPR <80% and MPR ≥80% groups, respectively. The mean prescription days ±SD in the MPR <80% and MPR ≥80% groups were 114.7 ± 9.1 and 1151.2 ± 22.5, respectively. S-K value with adjustment by covariates in MPR <80% and MPR ≥80% groups were 5.62 (95% CI: 5.57-5.68) and 5.72 (95% CI: 5.68-5.76) at index followed by 4.65 (95% CI: 4.58-4.71) and 4.57 (95% CI: 4.51-4.62) at 3M, respectively. The hazard ratios of incidence rates in hospitalization was 1.41 (p < 0.001), introduction of renal replacement therapy was 1.25 (p < 0.003), recurrent HK was 1.67 (p < 0.001), and decreased eGFR was 1.41 (p < 0.001), respectively. Conclusion: These results indicate a higher risk of adverse outcomes when PBs were not prescribed chronically, whereas S-K levels were similarly controlled. Chronic control with continued PBs rather than temporary treatment may be associated with the reduction of adverse clinical outcomes in patients with HK.

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Could the serum glucose/potassium ratio offer an early reliable predictor of life-threatening events in acute methylxanthine intoxication?

Methylxanthines are widely used to manage pulmonary disorders, particularly in developing countries. Methylxanthines are unsafe due to their narrow therapeutic index and associated morbidity and mortality. The current study aimed to investigate the role of glucose/potassium ratio as a substantially useful early predictor of life-threatening events (LTEs) in the form of cardiovascular and neurological complications among methylxanthine users. A retrospective cohort study was conducted using medical records of patients diagnosed with acute methylxanthine intoxications and presented to an Egyptian Poison Control Center for 2 years. A total of 366 patients were enrolled. Of them, 59 patients (16.1%) were complicated with LTEs. The most frequent serious arrhythmia was T wave inversion (45.6% of patients with LTEs). Laboratory investigations that could significantly predict LTEs were the random blood glucose and potassium levels, glucose/potassium ratio, pH, liver transaminases, HCO3 level, hemoglobin, and platelet count (P < 0.05). The glucose/potassium ratio was the best predictor of LTEs (odds ratio = 2.92, and 95% confidence interval = 2.02-4.23). With an excellent area under the curve (0.906) and at a cutoff of 2.44, that ratio could correctly classify the patients based on their risk of LTEs with an overall accuracy of 73% (sensitivity of 88% and specificity of 70%). The current study endorsed an important, feasible, and easily obtainable ratio that could predictor stratify the patients according to severity and risk of LTEs, which guides the decision-making and prioritizes the treatment lines in methylxanthine intoxicated patients.

Unlocking Deep and Fast Potassium-Ion Storage through Phosphorus Heterostructure.

Potassium-ion battery represents a promising alternative of conventional lithium-ion batteries in sustainable and grid-scale energy storage. Among various anode materials, elemental phosphorus (P) has been actively pursued owing to the ideal natural abundance, theoretical capacity, and electrode potential. However, the sluggish redox kinetics of elemental P has hindered fast and deep potassiation process toward the formation of final potassiation product (K3 P), which leads to inferior reversible capacity and rate performance. Here, it is shown that rational design on black/red P heterostructure can significantly improve K-ion adsorption, injection and immigration, thus for the first time unlocking K3 P as the reversible potassiation product for elemental P anodes. Density functional theory calculations reveal the fast adsorption and diffusion kinetics of K-ion at the heterostructure interface, which delivers a highly reversible specific capacity of 923 mAh g-1 at 0.05 A g-1 , excellent rate capability (335 mAh g-1 at 1 A g-1 ), and cycling performance (83.3% capacity retention at 0.8 A g-1 after 300 cycles). These results can unlock other sluggish and irreversible battery chemistries toward sustainable and high-performing energy storage.

Higher dietary magnesium and potassium intake are associated with lower body fat in people with impaired glucose tolerance.

Introduction: Obesity and diabetes are public health concerns worldwide, but few studies have examined the habitual intake of minerals on body composition in people with prediabetes. Methods: In this prospective cross-sectional study, 155 Chinese subjects with IGT [median age: 59 (53-62) years, 58% female] had an assessment of body composition including body fat percentage, oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and 3-day food records from nutritional programme analysis. Results: Dietary intake of minerals was negatively correlated with body fat. People with obesity had the lowest daily consumption of iron median (IQR) 10.3 (6.9-13.3) mg, magnesium 224 (181-282) mg, and potassium 1973 (1563-2,357) mg when compared to overweight [10.5 (8.0-14.5) mg, 273 (221-335) mg, and 2,204 (1720-2,650) mg] and normal weight individuals [13.2 (10.0-18.6) mg, 313 (243-368) mg, and 2,295 (1833-3,037) mg] (p = 0.008, <0.0001, and 0.013 respectively). Amongst targeted minerals, higher dietary magnesium and potassium intake remained significantly associated with lower body fat after the adjustment of age, gender, macronutrients, fibre, and physical activity. Conclusion: Dietary magnesium and potassium intake may be associated with lower body fat in people with impaired glucose tolerance. Inadequate dietary mineral intake may play contribute to obesity and metabolic disorders independent of macronutrients and fibre consumption.

Analysis of the main antioxidant enzymes in the roots of Tamarix ramosissima under NaCl stress by applying exogenous potassium (K+).

Introduction: Salinization affects more than 25% of the world's arable land, and Tamarix ramosissima Ledeb (T. ramosissima), the representative of Tamarix plants, is widely grown in salinized soil. In contrast, less is known about the mechanism of potassium's antioxidative enzyme activity in preventing NaCl stress damage to plants. Method: This study examined changes in root growth for T. ramosissima at 0h, 48h, and 168h, performed antioxidant enzyme activity assays, transcriptome sequencing, and non-targeted metabolite analysis to understand changes in their roots as well as changes in the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Quantitative real-time PCR (qRT-PCR) was used to identify differentially expressed genes (DEGs) and differential metabolites associated with antioxidant enzyme activities. Result: As the time increased, the results showed that compared with the 200 Mm NaCl group, the root growth of the 200 mM NaCl + 10 mM KCl group increased, the activities of SOD, POD and CAT increased the most, but the contents of hydrogen peroxide (H2O2) and Malondialdehyde (MDA) increased less. Meanwhile, 58 DEGs related to SOD, POD and CAT activities were changed during the application of exogenous K+ for 48h and 168h in T. ramosissima. Based on association analysis of transcriptomic and metabolomic data, we found coniferyl alcohol, which can act as a substrate to label catalytic POD. It is worth noting that Unigene0013825 and Unigene0014843, as POD-related genes, have positively regulated the downstream of coniferyl alcohol, and they have a significant correlation with coniferyl alcohol. Discussion: In summary, 48h and 168h of exogenous K+ applied to the roots of T. ramosissima under NaCl stress can resist NaCl stress by scavenging the reactive oxygen species (ROS) generated by high salt stress by enhancing the mechanism of antioxidant enzyme activity, relieving NaCl toxicity and maintaining growth. This study provides genetic resources and a scientific theoretical basis for further breeding of salt-tolerant Tamarix plants and the molecular mechanism of K+ alleviating NaCl toxicity.

Construction of Ultra-Stable Ultrathin Black Phosphorus Nanodisks Hybridized with Fe3 O4 Nanoclusters and Iron (V)-Oxo Complex for Efficient Potassium Storage.

The practical application of metalloid black phosphorus (BP) based anodes for potassium ion batteries (PIBs) is mainly impeded by its instability in air and irreversible/sluggish potassium -storage behaviors. Herein, w e purposefully conceptualize a two-dimensional composite, where ultrathin BP nanodisks with Fe3 O4 nanoclusters are hybridized with Lewis acid iron (V)-oxo complex (FC) nanosheets (denoted as BP@Fe3 O4 -NCs@FC). The introduced electron coordinate bridge between FC and BP, and hydrophobic surface of FC synergistically assure that BP@Fe3 O4 -NCs@FC is ultra-stable in humid air. With the purposeful structural and componential design, the resultant BP@Fe3 O4 -NCs@FC anode is endowed with appealing electrochemical performance in terms of reversible capacity, rate behavior and long-duration cycling stability in both half and full cells. Furthermore, the underlying formation and potassium-storage mechanisms of BP@Fe3 O4 -NCs@FC w ere tentatively proposed. The in-depth insights here will provide a crucial understanding in rational exploration of advanced anodes for next-generation PIBs. This article is protected by copyright. All rights reserved.

Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). CONCLUSION: The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

The Role of IAA in Regulating Root Architecture of Sweetpotato (Ipomoea batatas [L.] Lam) in Response to Potassium Deficiency Stress.

Plants can adapt to the spatial heterogeneity of soil nutrients by changing the morphology and architecture of the root system. Here, we explored the role of auxin in the response of sweetpotato roots to potassium (K+) deficiency stress. Two sweetpotato cultivars, Xushu 32 (low-K-tolerant) and Ningzishu 1 (low-K-sensitive), were cultured in low K+ (0.1 mmol L-1, LK) and normal K+ (10 mmol L-1, CK) nutrient solutions. Compared with CK, LK reduced the dry mass, K+ content, and K+ accumulation in the two cultivars, but the losses of Xushu 32 were smaller than those of Ningzishu 1. LK also affected root growth, mainly impairing the length, surface area, forks number, and crossings number. However, Xushu 32 had significantly higher lateral root length, density, and surface area than Ningzishu 1, closely related to the roots' higher indole-3-acetic acid (IAA) content. According to the qPCR results, Xushu 32 synthesized more IAA (via IbYUC8 and IbTAR2) in leaves but transported and accumulated in roots through polar transport (via IbPIN1, IbPIN3, and IbAUX1). It was also associated with the upregulation of auxin signaling pathway genes (IbIAA4 and IbIAA8) in roots. These results imply that IAA participates in the formation of lateral roots and the change in root architecture during the tolerance to low K+ stress of sweetpotato, thus improving the absorption of K+ and the formation of biomass.

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up.

RATIONALE & OBJECTIVE: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We followed 1714 patients (≥65y) from the European QUALity (EQUAL) study for eight years from their first eGFR <20ml/min/1.73m2 measurement. EXPOSURE: Serum potassium was measured every 3 to 6 months and categorized as: ≤3.5, >3.5-≤4.0, >4.0-≤4.5, >4.5-≤5.0 (reference), >5.0-≤5.5, >5.5-≤6.0 and >6.0 mmol/L. OUTCOME: The combined outcome death before KRT or start of KRT. ANALYTICAL APPROACH: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional-hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, RAAS inhibition (RAASi), eGFR and subjective global assessment (SGA). RESULTS: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease and 54% used RAASi. Their mean±SD age was 76±7 years, mean eGFR was 17±5 ml/min/1.73m2, mean SGA was 6.0±1.0. Over eight years, 414 (24%) died before starting KRT and 595 (35%) started KRT. Adjusted hazard ratios (HRs, 95%-CI) for death or KRT according to the potassium categories were: 1.6 (1.1-2.3), 1.4 (1.1-1.7), 1.1 (1.0-1.4), 1 (reference), 1.1 (0.9-1.4), 1.8 (1.4-2.3) and 2.2 (1.5-3.3). HRs were lowest at a potassium of about 4.9 mmol/L. LIMITATIONS: Shorter intervals between potassium measurements would have allowed for more precise estimations. CONCLUSIONS: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4-5, with a nadir risk at potassium level of 4.9 mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5.

Aspergillus aculeatus enhances nutrient uptake and forage quality in bermudagrass by increasing phosphorus and potassium availability.

Introduction: Potassium and phosphorus are essential macronutrients for plant growth and development. However, most P and K exist in insoluble forms, which are difficult for plants to directly absorb and utilize, thereby resulting in growth retardation of plants under P or K deficiency stress. The Aspergillus aculeatus fungus has growth-promoting characteristics and the ability to dissolve P and K. Methods: Here, to investigate the physiological effects of A. aculeatus on bermudagrass under P or K deficiency, A. aculeatus and bermudagrass were used as experimental materials. Results and discussion: The results showed that A. aculeatus could promote tolerance to P or K deficiency stress in bermudagrass, decrease the rate of leaf death, and increase the contents of crude fat as well as crude protein. In addition, A. aculeatus significantly enhanced the chlorophyll a+b and carotenoid contents. Moreover, under P or K deficiency stress, bermudagrass inoculated with A. aculeatus showed higher N, P, and K contents than non-inoculated plants. Furthermore, exogenous A. aculeatus markedly decreased the H2O2 level and CAT and POD activities. Based on our results, A. aculeatus could effectively improve the forage quality of bermudagrass and alleviate the negative effects of P or K deficiency stress, thereby playing a positive economic role in the forage industry.

Immunocytoprotection after reperfusion with Kv1.3 inhibitors has an extended treatment window for ischemic stroke.

Introduction: Mechanical thrombectomy has improved treatment options and outcomes for acute ischemic stroke with large artery occlusion. However, as the time window of endovascular thrombectomy is extended there is an increasing need to develop immunocytoprotective therapies that can reduce inflammation in the penumbra and prevent reperfusion injury. We previously demonstrated, that by reducing neuroinflammation, KV1.3 inhibitors can improve outcomes not only in young male rodents but also in female and aged animals. To further explore the therapeutic potential of KV1.3 inhibitors for stroke therapy, we here directly compared a peptidic and a small molecule KV1.3 blocker and asked whether KV1.3 inhibition would still be beneficial when started at 72 hours after reperfusion. Methods: Transient middle cerebral artery occlusion (tMCAO, 90-min) was induced in male Wistar rats and neurological deficit assessed daily. On day-8 infarction was determined by T2-weighted MRI and inflammatory marker expression in the brain by quantitative PCR. Potential interactions with tissue plasminogen activator (tPA) were evaluated in-vitro with a chromogenic assay. Results: In a direct comparison with administration started at 2 hours after reperfusion, the small molecule PAP-1 significantly improved outcomes on day-8, while the peptide ShK-223 failed to reduce infarction and neurological deficits despite reducing inflammatory marker expression. PAP-1 still provided benefits when started 72 hours after reperfusion. PAP-1 does not reduce the proteolytic activity of tPA. Discussion: Our studies suggest that KV1.3 inhibition for immunocytoprotection after ischemic stroke has a wide therapeutic window for salvaging the inflammatory penumbra and requires brain-penetrant small molecules.

Simulation test for impartment of use-dependent plasticity by inactivation of axonal potassium channels on hippocampal mossy fibers.

Modification of axonal excitability directly impacts information transfer through the neuronal networks in the brain. However, the functional significance of modulation of axonal excitability by the preceding neuronal activity largely remains elusive. One remarkable exception is the activity-dependent broadening of action potential (AP) propagating along the hippocampal mossy fibers. The duration of AP is progressively prolonged during repetitive stimuli and facilitated presynaptic Ca2+ entry and subsequent transmitter release. As an underlying mechanism, accumulated inactivation of axonal K+ channels during AP train has been postulated. As the inactivation of axonal K+ channels proceeds on a timescale of several tens of milliseconds slower than the millisecond scale of AP, the contribution of K+ channel inactivation in AP broadening needs to be tested and evaluated quantitatively. Using the computer simulation approach, this study aimed to explore the effects of the removal of the inactivation process of axonal K+ channels in the simple but sufficiently realistic model of hippocampal mossy fibers and found that the use-dependent AP broadening was completely abolished in the model replaced with non-inactivating K+ channels. The results demonstrated the critical roles of K+ channel inactivation in the activity-dependent regulation of axonal excitability during repetitive action potentials, which critically imparts additional mechanisms for robust use-dependent short-term plasticity characteristics for this particular synapse.

Post-exercise rehydration: Comparing the efficacy of three commercial oral rehydration solutions.

Introduction: This study compared the efficacy of three commercial oral rehydration solutions (ORS) for restoring fluid and electrolyte balance, after exercise-induced dehydration. Method: Healthy, active participants (N = 20; ♀ = 3; age ∼27 y, V˙O2peak ∼52 ml/kg/min) completed three randomised, counterbalanced trials whereby intermittent exercise in the heat (∼36°C, ∼50% humidity) induced ∼2.5% dehydration. Subsequently, participants rehydrated (125% fluid loss in four equal aliquots at 0, 1, 2, 3 h) with a glucose-based (G-ORS), sugar-free (Z-ORS) or amino acid-based sugar-free (AA-ORS) ORS of varying electrolyte composition. Urine output was measured hourly and capillary blood samples collected pre-exercise, 0, 2 and 5 h post-exercise. Sodium, potassium, and chloride concentrations in urine, sweat, and blood were determined. Results: Net fluid balance peaked at 4 h and was greater in AA-ORS (141 ± 155 ml) and G-ORS (101 ± 195 ml) than Z-ORS (-47 ± 208 ml; P ≤ 0.010). Only AA-ORS achieved positive sodium and chloride balance post-exercise, which were greater for AA-ORS than G-ORS and Z-ORS (P ≤ 0.006), as well as for G-ORS than Z-ORS (P ≤ 0.007) from 1 to 5 h. Conclusion: when provided in a volume equivalent to 125% of exercise-induced fluid loss, AA-ORS produced comparable/superior fluid balance and superior sodium/chloride balance responses to popular glucose-based and sugar-free ORS.

The miR166d/TaCPK7-D Signaling Module Is a Critical Mediator of Wheat (Triticum aestivum L.) Tolerance to K+ Deficiency.

It is well established that potassium (K+) is an essential nutrient for wheat (Triticum aestivum L.) growth and development. Several microRNAs (miRNAs), including miR166, are reportedly vital roles related to plant growth and stress responses. In this study, a K+ starvation-responsive miRNA (miR166d) was identified, which showed increased expression in the roots of wheat seedlings exposed to low-K+ stress. The overexpression of miR166d considerably increased the tolerance of transgenic Arabidopsis plants to K+ deprivation treatment. Furthermore, disrupting miR166d expression via virus-induced gene silencing (VIGS) adversely affected wheat adaptation to low-K+ stress. Additionally, miR166d directly targeted the calcium-dependent protein kinase 7-D gene (TaCPK7-D) in wheat. The TaCPK7-D gene expression was decreased in wheat seedling roots following K+ starvation treatment. Silencing TaCPK7-D in wheat increased K+ uptake under K+ starvation. Moreover, we observed that the miR166d/TaCPK7-D module could affect wheat tolerance to K+ starvation stress by regulating TaAKT1 and TaHAK1 expression. Taken together, our results indicate that miR166d is vital for K+ uptake and K+ starvation tolerance of wheat via regulation of TaCPK7-D.

Unveiling the Nature of Ultrastable Potassium Storage in Bi0.48Sb1.52Se3 Composite.

The conversion and alloying-type anodes for potassium-ion batteries (PIBs) have drawn attention. However, it is still a challenge to relieve the huge volume expansion/electrode pulverization. Herein, we synthesized a composite material comprising Bi0.48Sb1.52Se3 nanoparticles uniformly dispersed in carbon nanofibers (Bi0.48Sb1.52Se3@C). Benefiting from the synergistic effects of the high electronic conductivity of Bi0.48Sb1.52Se3 and the mechanical confinement of the carbon fiber that buffers the large chemomechanical stress, the Bi0.48Sb1.52Se3@C//K half cells deliver a high reversible capacity (491.4 mAh g-1, 100 cycles at 100 mA g-1) and an extraordinary cyclability (80% capacity retention, 1000 cycles at 1000 mA g-1). Furthermore, the Bi0.48Sb1.52Se3@C-based PIB full cells achieve a high energy density of 230 Wh kg-1. In situ transmission electron microscopy (TEM) reveals an intercalation, conversion, and alloying three-step reaction mechanism and a reversible amorphous transient phase. More impressively, the nanofiber electrode can almost return to its original diameter after the potassiation and depotassiation reaction, indicating a highly reversible volume change process, which is distinct from the other conversion type electrodes. This work reveals the stable potassium storage mechanisms of Bi0.48Sb1.52Se3@C composite material, which provides an effective strategy to enable conversion/alloying-type anodes for high performance PIBs for energy storage applications.

The Potassium Channel Blocker ß-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity.

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the Bungarus multicinctus krait venom using the ciliate Tetrahymena pyriformis as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against T. pyriformis was analyzed. As a result, 21 kDa protein toxic to Tetrahymena was isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by ß-bungarotoxin (ß-Bgt) differing from the known toxins by two amino acid residues. Inactivation of ß-Bgt phospholipolytic activity with p-bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of ß-Bgt, which is shown to be independent of its phospholipolytic activity.

Surface modification of cellulose with succinic anhydride in dimethyl sulfoxide using potassium carbonate as a catalyst.

Cellulose succinates (CSs) having degrees of substitution (DSs) ranging from 0.78 to 2.77 were successfully obtained by reacting cellulose with succinic anhydride (SA) in dimethyl sulfoxide at room temperature using a small amount of inexpensive solid potassium carbonate as a catalyst. Interestingly, CSs with higher DS values were obtained with a much smaller amount of catalyst than previously reported. Moreover, it is possible to control the DS by tailoring the reaction time and mass ratio of cellulose/SA. The hydroxyl groups at the C-6, C-2, and C-3 positions were the main esterification positions. In this process, most of the raw materials are either incorporated into the product or are recoverable. The E-factor, which reflects the sustainability of a given process, was demonstrated to be reduced by 93% by recovering the raw materials.

The second intracellular loop of the yeast Trk1 potassium transporter is involved in regulation of activity, and interaction with 14-3-3 proteins.

Potassium is an essential intracellular ion, and a sufficient intracellular concentration of it is crucial for many processes; therefore it is fundamental for cells to precisely regulate K+ uptake and efflux through the plasma membrane. The uniporter Trk1 is a key player in K+ acquisition in yeasts. The TRK1 gene is expressed at a low and stable level; thus the activity of the transporter needs to be regulated at a posttranslational level. S. cerevisiae Trk1 changes its activity and affinity for potassium ion quickly and according to both internal and external concentrations of K+, as well as the membrane potential. The molecular basis of these changes has not been elucidated, though phosphorylation is thought to play an important role. In this study, we examined the role of the second, short, and highly conserved intracellular hydrophilic loop of Trk1 (IL2), and identified two phosphorylable residues (Ser882 and Thr900) as very important for 1) the structure of the loop and consequently for the targeting of Trk1 to the plasma membrane, and 2) the upregulation of the transporter's activity reaching maximal affinity under low external K+ conditions. Moreover, we identified three residues (Thr155, Ser414, and Thr900) within the Trk1 protein as strong candidates for interaction with 14-3-3 regulatory proteins, and showed, in an in vitro experiment, that phosphorylated Thr900 of the IL2 indeed binds to both isoforms of yeast 14-3-3 proteins, Bmh1 and Bmh2.

Acute hyperkalemia in adults.

Hyperkalemia is a common, life-threatening medical situation in chronic renal disease patients in the emergency department (ED). Since hyperkalemia does not present with any specific symptom, it is difficult to diagnose clinically. Hyperkalemia causes broad and dramatic medical presentations including cardiac arrhythmia and sudden death. Hyperkalemia is generally determined through serum measurement in the laboratory. Treatment includes precautions to stabilize cardiac membranes, shift potassium from the extracellular to the intracellular, and increase potassium excretion. The present article discusses the management of hyperkalemia in the ED in the light of current evidence.