Harmonising IV Oxycodone with Paediatric Perioperative Medications: A Compatibility Study Through Y-Type Connectors.

Purpose: Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids. Methods: Mixtures of oxycodone (1mg.mL-1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150. Results: IV oxycodone (1 mg.mL-1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested. Conclusion: According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL-1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.

Potassium Intake and Human Health.

Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].

The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.

The neuron-specific K+/Cl- co-transporter 2, KCC2, which is critical for brain development, regulates γ-aminobutyric acid-dependent inhibitory neurotransmission. Consistent with its function, mutations in KCC2 are linked to neurodevelopmental disorders, including epilepsy, schizophrenia, and autism. KCC2 possesses 12 transmembrane spans and forms an intertwined dimer. Based on its complex architecture and function, reduced cell surface expression and/or activity have been reported when select disease-associated mutations are present in the gene encoding the protein, SLC12A5. These data suggest that KCC2 might be inherently unstable, as seen for other complex polytopic ion channels, thus making it susceptible to cellular quality control pathways that degrade misfolded proteins. To test these hypotheses, we examined KCC2 stability and/or maturation in five model systems: yeast, HEK293 cells, primary rat neurons, and rat and human brain synaptosomes. Although studies in yeast revealed that KCC2 is selected for endoplasmic reticulum-associated degradation (ERAD), experiments in HEK293 cells supported a more subtle role for ERAD in maintaining steady-state levels of KCC2. Nevertheless, this system allowed for an analysis of KCC2 glycosylation in the ER and Golgi, which serves as a read-out for transport through the secretory pathway. In turn, KCC2 was remarkably stable in primary rat neurons, suggesting that KCC2 folds efficiently in more native systems. Consistent with these data, the mature glycosylated form of KCC2 was abundant in primary rat neurons as well as in rat and human brain. Together, this work details the first insights into the influence that the cellular and membrane environments have on several fundamental KCC2 properties, acknowledges the advantages and disadvantages of each system, and helps set the stage for future experiments to assess KCC2 in a normal or disease setting.

Partial Replacement of NaCl with KCl in Cooked Meat Could Reduce the Liver Damage Through Renin-Angiotensin System in Mice.

SCOPE: Dietary salt (sodium chloride, NaCl) is necessary for processed meat products, but intake of a high-sodium diet carries serious health risks. Considerable studies indicate that the partial substitution of NaCl with potassium chloride (KCl) can produce sodium-reduced cooked meat. However, most studies of sodium-reduced cooked meat focus on the production process in vitro, and the effect of cooked meat on health has not been well clarified in vivo. METHODS AND RESULTS: This study finds that compared to the high-sodium group (HS), serum renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and the levels of some indicators of dyslipidemia are decreased in the reduced salt by partial substitution of NaCl with KCl group (RS + K). Furthermore, RS + K increases the antioxidation abilities, inhibits the renin-angiotensin system (RAS) through ACE/Ang II/Ang II type 1 receptor axis pathway, reduces synthesis of triglyceride and cholesterol and protein expressions of inflammatory factors interleukin-17A and nuclear factor-kappa B in the liver. CONCLUSION: Partial substitution of NaCl with KCl in cooked meat can be a feasible approach for improving the health benefits and developing novel functional meat products for nutritional health interventions.

Anesthesia and humane euthanasia methods for king worm larvae (Zophobas morio).

A growing spotlight on insect welfare as research subjects, fodder for vertebrate animals, and patients for veterinarians highlights the need to establish humane euthanasia methods for these species. An insect of increasing commercial importance is the king worm (Zophobas morio), a type of darkling beetle larvae. The initial objective of this study was to determine if prolonged exposure to isoflurane would lengthen anesthetic recovery and lead to euthanasia. Larvae were exposed to isoflurane for 10 min, 40 min, 70 min, 190 min, 13 h, and 24 h (n = 10 for each treatment duration group), and time to recovery was subsequently monitored in room air. The second objective was to determine effectiveness of secondary euthanasia methods: injectable potassium chloride at 1 mg/g body weight (n = 5) and 3 mg/g body weight (n = 5) doses; immersion in 200 proof ethanol (n = 10), 10% buffered formalin (n = 10), and water (n = 10); and freezing at -18°C (n = 10). Prolonged exposure to isoflurane led to extended recovery times, but 100% mortality was not achieved. Submersion in ethanol and injection of potassium chloride at a 3 mg/g body weight dose resulted in 100% mortality. If these larvae are to be used as future food sources, a humane euthanasia method that preserves the ability to be consumed is required.

Comparing a range of potassium-enriched low sodium salt substitutes to common salt: Results of taste and visual tests in South African adults.

BACKGROUND AND AIMS: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. METHODS AND RESULTS: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. CONCLUSION: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.

Potassium-Enriched Salt Substitutes: A Review of Recommendations in Clinical Management Guidelines.

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Mouse TMC4 is involved in the detection of chloride taste of salts.

Licking behavior with various salts in transmembrane channel-like 4 (Tmc4) knockout (KO) mice was observed. In Tmc4 KO mice, a significant decrease in sensitivity to chloride salts, such as NaCl, KCl, and NH4Cl, was observed, while no significant decrease in sensitivity to Na-gluconate was observed. This finding suggests that TMC4 may be involved in the detection of chloride taste.

Relaxant Effects of Piperine and Piperlongumine from Piper longum Fruits on Porcine Coronary Artery.

Since ancient times, Piper longum Linn. fruits have been recognized for exhibiting various effects, including the diaphoretic effects linked to enhanced blood flow. Piperine and piperlongumine coexist in Piper longum Linn. fruits, although the cardiovascular effects of both compounds remain elusive. We investigated their action of piperine and piperlongumine in porcine coronary arteries, comparing them to the Ca2+ channel antagonist diltiazem. Piperlongumine, unlike piperine or diltiazem, concentration-dependently inhibited basal contractile tone in endothelium-denuded coronary arteries. All three compounds inhibit tonic contractions induced by high potassium chloride (KCl) concentrations. The order of relaxation potency indexed by the half-maximal effective concentration (EC50) were as follows: diltiazem > piperlongumine > piperine. These effects were not different between endothelium-intact and -denuded preparations. In endothelial-denuded preparations, pretreatment with these compounds not only inhibited KCl-induced tonic contractions attenuated calcium chloride (CaCl2)-induced ones in a Ca2+-free medium. Histamine-induced phasic contractions in a Ca2+-free medium containing intracellular Ca2+ chelator was completely suppressed by selective inositol trisphosphate receptor antagonist and piperlongumine, whereas piperine or diltiazem do not have the same effect. These findings suggest that piperine and piperlongumine similar to diltiazem cause vasorelaxation by inhibiting both KCl- and CaCl2-induced contractions in coronary arteries, possibly through the inhibition of voltage-dependent Ca2+ channels. Piperlongumine inhibits histamine-induced contractions in a Ca2+-free medium, which is associated with the intracellular Ca2+ signaling pathway, suggesting that the relaxant effect of piperlongumine differs from that of piperine.

Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.

PURPOSE: The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery. METHODS: Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance. RESULTS: The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL-1; 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL-1; 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03). CONCLUSION: Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03699462); first posted 9 October 2018.

RéSUMé: OBJECTIF: L'intégrité du glycocalyx endothélial (GE), un acteur essentiel de l'homéostasie vasculaire, influencerait le devenir des patient·es gravement malades. Nous avons étudié l'effet de l'albumine à 5 %, qui préservait l'intégrité du GE dans les études précliniques, par rapport à une solution cristalloïde équilibrée sur la dégradation du GE chez les patient·es bénéficiant d'une chirurgie coronarienne à cœur battant. MéTHODE: Les patient·es ont été randomisé·es à recevoir soit de l'albumine à 5 % (N = 51) ou de la solution cristalloïde équilibrée (Plasma-Lyte [Baxter Incorporated, Séoul, République de Corée]; N = 53) pour le remplacement du volume intraveineux pendant la chirurgie (en double aveugle). Le critère d'évaluation principal était la concentration plasmatique de syndécan-1, un marqueur de la dégradation du GE, mesurée après l'induction de l'anesthésie (ligne de base), la fin de la greffe et la fermeture du sternum. Les critères d'évaluation secondaires étaient le peptide natriurétique auriculaire (ANP), le facteur de nécrose tumorale (TNF)-α, la thrombomoduline soluble et le bilan hydrique périopératoire. RéSULTATS: Les besoins liquidiens moyens (écart type) étaient de 833 (270) mL et 1323 (492) mL dans les groupes albumine et Plasma-Lyte, respectivement (différence moyenne, −489 mL; intervalle de confiance [IC] à 95 %, −643 à −335; P < 0,001). La concentration plasmatique de syndécan-1 a augmenté après la fin de la greffe (différence médiane, 116 ng·mL−1; IC 95 %, 67 à 184; P < 0,001) et la fermeture du sternum (différence médiane, 57 ng·mL−1; IC 95 %, 36 à 80; P < 0,001) par rapport aux concentrations au départ, sans différences intergroupe. Les concentrations de peptide natriurétique auriculaire, de TNF-α et de thrombomoduline soluble étaient similaires entre les deux groupes. La quantité de drainage du drain thoracique était plus importante dans le groupe albumine que dans le groupe Plasma-Lyte (différence médiane, 190 mL; IC 95 %, 18 à 276; P = 0,03). CONCLUSION: La chirurgie coronarienne à cœur battant a été associée à une dégradation significative du glycocalyx endothélial. Pourtant, la fluidothérapie peropératoire avec 5 % d'albumine n'a pas pu améliorer la dégradation du GE par rapport à une solution cristalloïde équilibrée. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03699462); enregistrée pour la première fois le 9 octobre 2018.

[Inability of hospital computerised physician order entry systems to secure the use of concentrated potassium intravenous solutions]. / Incapacité des logiciels d'aide à la prescription hospitaliers à sécuriser l'utilisation des solutions concentrées de potassium injectable.

OBJECTIVES: To determine whether hospital computerised physician order entry (CPOE) systems contribute to securing intravenous potassium chloride (KCl) prescriptions with reference to the recommendations issued by French healthcare agencies. METHODS: We sent a questionnaire to the members of the Association pour le Digital et l'Information en Pharmacie. RESULTS: More than three quarters of the 84 responses received involving 23 CPOE systems indicate that it is possible to: prescribe an ampoule of concentrated potassium chloride 10% 10mL intravenously without any diluents (80%); prescribe 4g of KCl in a bag of 500mL of NaCl 0,9% (98%); prescribe a solution that contains 6 grams of KCl per liter (94%); prescribe the administration of an injectable ampoule orally by means of a free text comment (83%). Nearly half of the responses indicate that it is possible to prescribe: concentrated KCl ampoules as administration solvent (50%); an injectable vial to be administered by oral route (52%). CONCLUSION: At least 23 hospital CPOE systems are unable to secure the prescriptions of injectable KCl. This finding lifts the veil on an unthought, namely the role of CPOE systems in securing high-risk medications. In order to solve this problem, it should be mandatory that health information technology vendors pay particular attention to these drugs. With regard to injectable KCl, the utilisation of a dilution vehicle, maximum concentration and maximum infusion flow rate are the first four constraints to be satisfied.

Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study.

BACKGROUND: We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome. METHODS: Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417). CONCLUSION: IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.

Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review.

OBJECTIVE: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022. STUDY SELECTION AND DATA EXTRACTION: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use. DATA SYNTHESIS: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline. CONCLUSION AND RELEVANCE: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.

Genome-Wide 5-Formylcytosine Redistribution in KCl-Stimulated Mouse Primary Cortical Neurons is Associated with Neuronal Activity.

An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.

POTASSIUM CHLORIDE ADMINISTERED VIA FOUR ROUTES FOR EUTHANASIA OF ANESTHETIZED GOLDFISH (CARASSIUS AURATUS).

Immersion overdose in tricaine methanesulfonate (MS-222) is ineffective for euthanasia of adult goldfish (Carassius auratus), and investigation of alternative techniques is warranted. This study evaluated potassium chloride (KCl) administered via four routes for goldfish euthanasia. Thirty clinically healthy adult goldfish (17.2-41.9 g) were anesthetized via immersion in buffered MS-222 (300 mg/L) for 5 min beyond anesthetic induction. Fish were then randomly administered one of five treatments: KCl (333 mg/mL, 4.5 mmol/mL, 4.5 mEq/mL) via intracardiac injection at 10 mEq/kg (IC), intracoelomic injection (ICe) or bilateral topical delivery over the gill filaments (T) at 100 mEq/kg, or 90-min immersion at 4,500 mEq/L (saturated solution) dissolved in induction solution (water [W]), or no treatment (control [C]). Following treatment, all fish were moved to anesthetic-free freshwater. Serial heart rates were collected via Doppler device until sound cessation or recovery. Median (range) time to perform treatments was 5.3 (1.2-8.0) min, 3 (3-3) s, and 10 (10-10) s in IC, ICe, and T, respectively. Doppler cessation occurred in 6/6, 6/6, 6/6, 6/6, and 0/6 fish in median (range) times of 3 (0-210), 18 (10-45), 118 (90-390), and 150 (60-240) min in IC, ICe, T, W, and C, respectively; this was significantly different between groups (P = 0.002). Following or during treatment, 1/6, 2/6, 6/6, and 4/6 fish in IC, ICe, T, and W, respectively, exhibited intermittent transient jerking movements. Median (range) time to recovery in C was 5.5 (3.5-6.5) min. All administration routes were effective, but time to Doppler cessation varied and transient movements were noted. Preliminary follow-up research determined that return to MS-222 induction solution following ICe KCl treatment abolished movements. ICe KCl at 100 mEq/kg was technically simple and resulted in Doppler sound cessation in a clinically relevant time frame in 6/6 anesthetized goldfish. Return to MS-222 immersion following KCl administration is recommended.

Hypomagnesemia with Secondary Hypocalcemia (HSH): a Case Report.

BACKGROUND: Hypomagnesemia with secondary hypocalcemia (HSH) is a genetic disorder arising from the body's impaired capacity to absorb and retain magnesium (Mg2+) consumed through diet. Consequently, Mg2+ levels in blood are significantly reduced, a condition referred to as hypomagnesemia. Insufficient levels of Mg2+ and calci-um (Ca2+) can lead to neurological complications that manifest during infancy, such as painful muscle spasms (tet-any) and seizures. METHODS: We reported a case of HSH involving a 10-year-old male patient from a Han Chinese family. He was admitted due to recurrent convulsions experienced over the past two years. The patient's initial episode occurred two years prior, when he collapsed without apparent cause and exhibited limb numbness, convulsions, and a disordered state of consciousness, accompanied by hypocalcemia. Cranial CT scans revealed multiple symmetrical calcifications in the basal ganglia, corona radiata, and cerebellar dentate nucleus. RESULTS: During the hospital stay, the patient was administered the following treatments: Calcium Carbonate and Vitamin D3 Tablets (1.5 g of calcium carbonate and 125 IU of Vitamin D3 per tablet, 1 tablet/time) once daily, Calcitriol Soft Capsules (0.25 µg of calcitriol per capsule, 1 capsule/time) twice daily, Potassium Chloride Sustained-release Tablets (0.5 g of potassium chloride per tablet, 1 tablet/time) thrice daily, Potassium Aspartate and Mag-nesium Aspartate Tablets (158 mg of potassium aspartate and 140 mg of magnesium aspartate per tablet, 1 tablet/ time) thrice daily, and intravenous infusions of Magnesium Sulfate Injection (2.5 g/time) twice daily. After three days in the hospital, the patient's initial symptoms subsided, resulting in discharge with a prescription of ongoing oral medications including Calcium Carbonate and Vitamin D3 Tablets, Calcitriol Soft Capsules, and Potassium Aspartate and Magnesium Aspartate Tablets, with the same usage and dosage as the above three drugs. A month subsequent, the serum levels of Mg2+, Ca2+, potassium (K+), and phosphorus were 0.96 mmol/L, 2.52 mmol/L, 4.06 mmol/L, and 1.63 mmol/L, respectively. CONCLUSIONS: Primary HSH is an uncommon manifestation of parathyroid hypoplasia, clinically characterized by low levels of Mg2+, Ca2+, and K+ in the blood. Our findings serve to enrich and consolidate the knowledge for future case studies and follow-up investigations.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

BACKGROUND: Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. METHODS: Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. RESULTS: The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. CONCLUSIONS: KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Effects of isoflurane and urethane anesthetics on glutamate neurotransmission in rat brain using in vivo amperometry.

BACKGROUND: Aspects of glutamate neurotransmission implicated in normal and pathological conditions are predominantly evaluated using in vivo recording paradigms in rats anesthetized with isoflurane or urethane. Urethane and isoflurane anesthesia influence glutamate neurotransmission through different mechanisms; however, real-time outcome measures of potassium chloride (KCl)-evoked glutamate overflow and glutamate clearance kinetics have not been compared within and between regions of the brain. In order to maintain rigor and reproducibility within the literature between the two most common methods of anesthetized in vivo recording of glutamate, we compared glutamate signaling as a function of anesthesia and brain region in the rat strain most used in neuroscience. METHODS: In the following experiments, in vivo amperometric recordings of KCl-evoked glutamate overflow and glutamate clearance kinetics (uptake rate and T80) in the cortex, hippocampus, and thalamus were performed using glutamate-selective microelectrode arrays (MEAs) in young adult male, Sprague-Dawley rats anesthetized with either isoflurane or urethane. RESULTS: Potassium chloride (KCl)-evoked glutamate overflow was similar under urethane and isoflurane anesthesia in all brain regions studied. Analysis of glutamate clearance determined that the uptake rate was significantly faster (53.2%, p < 0.05) within the thalamus under urethane compared to isoflurane, but no differences were measured in the cortex or hippocampus. Under urethane, glutamate clearance parameters were region-dependent, with significantly faster glutamate clearance in the thalamus compared to the cortex but not the hippocampus (p < 0.05). No region-dependent differences were measured for glutamate overflow using isoflurane. CONCLUSIONS: These data support that amperometric recordings of KCl-evoked glutamate under isoflurane and urethane anesthesia result in similar and comparable data. However, certain parameters of glutamate clearance can vary based on choice of anesthesia and brain region. In these circumstances, special considerations are needed when comparing previous literature and planning future experiments.