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Medicine Mar 2024Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is... (Review)
Review
RATIONALE
Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death.
PATIENT CONCERNS
A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin.
DIAGNOSES
The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005.
INTERVENTIONS
The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus.
OUTCOMES
The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015.
LESSONS
This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.
Topics: Humans; Female; Adult; Hyponatremia; Breast Neoplasms; Diabetes Insipidus; Cyclophosphamide; Sodium; Doxorubicin; Pituitary Hormones, Posterior; Diabetes Mellitus
PubMed: 38552085
DOI: 10.1097/MD.0000000000037572 -
Nutrients Mar 2024Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].
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 [...].
Topics: Humans; Potassium; Chlorides; Potassium Chloride
PubMed: 38542744
DOI: 10.3390/nu16060833 -
Toxins Feb 2024Ciguatoxins (CTXs) are neurotoxins responsible for ciguatera poisoning (CP), which affects more than 50,000 people worldwide annually. The development of analytical...
Ciguatoxins (CTXs) are neurotoxins responsible for ciguatera poisoning (CP), which affects more than 50,000 people worldwide annually. The development of analytical methods to prevent CP is a pressing global issue, and the N2a assay is one of the most promising methods for detecting CTXs. CTXs are highly toxic, and an action level of 0.01 μg CTX1B equivalent (eq)/kg in fish has been proposed. It is desirable to further increase the detection sensitivity of CTXs in the N2a assay to detect such low concentrations reliably. The opening of voltage-gated sodium channels (Na channels) and blocking of voltage-gated potassium channels (K channels) are thought to be involved in the toxicity of CTXs. Therefore, in this study, we developed an assay that could detect CTXs with higher sensitivity than conventional N2a assays, using K channel inhibitors as sensitizing reagents for N2a cells. The addition of the K channel inhibitors 4-aminopyridine and tetraethylammonium chloride to N2a cells, in addition to the traditional sensitizing reagents ouabain and veratridine, increased the sensitivity of N2a cells to CTXs by up to approximately 4-fold. This is also the first study to demonstrate the influence of K channels on the toxicity of CTXs in a cell-based assay.
Topics: Humans; Animals; Ciguatoxins; Ciguatera Poisoning; Aminopyridines; Potassium Channels, Voltage-Gated; Neuroblastoma
PubMed: 38535783
DOI: 10.3390/toxins16030118 -
Drug Design, Development and Therapy 2024Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of...
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) 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) 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 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.
Topics: Humans; Child; Oxycodone; Infusions, Intravenous; Potassium Chloride; Vancomycin; Glucose
PubMed: 38533429
DOI: 10.2147/DDDT.S444581 -
RSC Advances Mar 2024Sch. Bip is an endemic plant commonly employed in the Andes culture to counteract the effects of mountain sickness, and its bioactive molecules could provide new drugs...
Sch. Bip is an endemic plant commonly employed in the Andes culture to counteract the effects of mountain sickness, and its bioactive molecules could provide new drugs for treating hypertension. The purpose was to determine whether the vascular response of the plant bioactive molecules, such as (5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane; Sn-I), could be improved by a simple structural modification to synthesize oximes (Ox-Sn-I). We characterized both compounds using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). We investigated vascular relaxation mechanisms in response to Sn-I and Ox-Sn-I using rat aorta and vascular smooth muscle cells (A7r5) as experimental models. Preincubation of aortic rings with Sn-I (10 M) significantly ( < 0.001) decreased the contractile effect in response to phenylephrine (PE) and potassium chloride (KCl). The sensitivity (EC) to PE significantly ( < 0.01) decreased in the presence of Sn-I (10 M), but not with Ox-Sn-I. Sn-I significantly ( < 0.001) reduced the PE-induced contraction under calcium-free conditions. When A7r5 cells were preincubated with Sn-I and Ox-Sn-I (10 M), both compounds blunted the increase in intracellular Ca induced by KCl. 2,3-Dihydrobenzofurane derived from (Sn-I) reduces the contractile response probably by blocking Ca entry through voltage-gated Ca channels (VGCC) in vascular smooth cells. This effect also causes relaxation in rat aorta mediated by reduction of intracellular Ca concentration, rather than an increase of NO generation in endothelial vascular cells.
PubMed: 38528924
DOI: 10.1039/d4ra01058b -
ACS Omega Mar 2024The increased concentration of lead (Pb) in soils is a serious threat to human beings and plants all over the world. Salinity stress is also a major issue across the...
The increased concentration of lead (Pb) in soils is a serious threat to human beings and plants all over the world. Salinity stress is also a major issue across the globe, which limits crop productivity. The use of allelochemicals has become an effective strategy to mitigate the toxic effects of abiotic stresses. Sorghum is an important crop grown across the globe, and it also possesses an appreciably allelopathic potential. Therefore, this study was planned to determine the impacts of the sorghum water extract (SWE) on improving maize growth under Pb and salinity stress. The experiment included different treatments; control, SWE (3%), and different levels of Pb and salinity stress; : control, : 50 mM NaCl, : 100 mM NaCl, : 250 μM Pb, and : 500 μM Pb. Lead and salinity stress reduced the maize growth by the genesis of reactive oxygen species (ROS), as evidenced by higher production of malondialdehyde (MDA: 39.1 and 32.28%) and hydrogen peroxide (HO: 20.62 and 17.81%). Spraying plants with SWE improved the maize growth by increasing antioxidant activities (ascorbate peroxidase: APX, catalase: CAT, peroxidase: POD and superoxide dismutase: SOD), photosynthetic pigments, relative water contents (RWC), osmolyte accumulation (proline, total soluble proteins: TSP, free amino acids: FAA), potassium accumulation, and decreasing MDA, HO, sodium, chloride, and Pb accumulation. In conclusion, the application of SWE mitigates adverse impacts of Pb and salinity stresses by improving chlorophyll synthesis and osmolyte accumulation, activating the antioxidant defense system, and preventing the entry of toxic ions.
PubMed: 38524408
DOI: 10.1021/acsomega.3c09495 -
Microbial Cell Factories Mar 2024The halophilic bacterium Halomonas elongata is an industrially important strain for ectoine production, with high value and intense research focus. While existing...
BACKGROUND
The halophilic bacterium Halomonas elongata is an industrially important strain for ectoine production, with high value and intense research focus. While existing studies primarily delve into the adaptive mechanisms of this bacterium under fixed salt concentrations, there is a notable dearth of attention regarding its response to fluctuating saline environments. Consequently, the stress response of H. elongata to salt shock remains inadequately understood.
RESULTS
This study investigated the stress response mechanism of H. elongata when exposed to NaCl shock at short- and long-time scales. Results showed that NaCl shock induced two major stresses, namely osmotic stress and oxidative stress. In response to the former, within the cell's tolerable range (1-8% NaCl shock), H. elongata urgently balanced the surging osmotic pressure by uptaking sodium and potassium ions and augmenting intracellular amino acid pools, particularly glutamate and glutamine. However, ectoine content started to increase until 20 min post-shock, rapidly becoming the dominant osmoprotectant, and reaching the maximum productivity (1450 ± 99 mg/L/h). Transcriptomic data also confirmed the delayed response in ectoine biosynthesis, and we speculate that this might be attributed to an intracellular energy crisis caused by NaCl shock. In response to oxidative stress, transcription factor cysB was significantly upregulated, positively regulating the sulfur metabolism and cysteine biosynthesis. Furthermore, the upregulation of the crucial peroxidase gene (HELO_RS18165) and the simultaneous enhancement of peroxidase (POD) and catalase (CAT) activities collectively constitute the antioxidant defense in H. elongata following shock. When exceeding the tolerance threshold of H. elongata (1-13% NaCl shock), the sustained compromised energy status, resulting from the pronounced inhibition of the respiratory chain and ATP synthase, may be a crucial factor leading to the stagnation of both cell growth and ectoine biosynthesis.
CONCLUSIONS
This study conducted a comprehensive analysis of H. elongata's stress response to NaCl shock at multiple scales. It extends the understanding of stress response of halophilic bacteria to NaCl shock and provides promising theoretical insights to guide future improvements in optimizing industrial ectoine production.
Topics: Sodium Chloride; Halomonas; Osmotic Pressure; Amino Acids, Diamino; Gene Expression Profiling; Peroxidases
PubMed: 38519954
DOI: 10.1186/s12934-024-02358-5 -
European Heart Journal May 2024Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported.
METHODS
NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130.
RESULTS
Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo.
CONCLUSIONS
In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.
Topics: Humans; Coronary Angiography; Contrast Media; Male; Female; Acute Coronary Syndrome; Double-Blind Method; Nitrates; Acute Kidney Injury; Aged; Middle Aged; Glomerular Filtration Rate; Potassium Compounds
PubMed: 38513060
DOI: 10.1093/eurheartj/ehae100 -
ChemistryOpen Mar 2024Solid state nanochannels provide significant practical advantages in many fields due to their interesting properties, such as controllable shape and size, robustness,...
Solid state nanochannels provide significant practical advantages in many fields due to their interesting properties, such as controllable shape and size, robustness, ion selectivity. But their complex preparation processes severely limit their application. In this study, a simple cost-effective method to fabricate single nanochannel by embedding a single polyethylene oxide (PEO) nanofiber is presented. Firstly, PEO nanofibers are prepared by electrospinning, and then a single PEO nanofiber are precisely transferred to the target sample using a micromanipulation platform. Then, PDMS is used for embedding, and finally, the PEO nanofiber is dissolved to obtain a single nanochannel. Unlike other methods of preparing nanochannels by embedding nanofibers, this method can prepare single nanochannel. The diameter of nanochannel can be as fine as 100 nm, and the length can reach several micrometers. The power generation between two potassium chloride solutions with various combinations of concentrations was investigated using the nanochannel. This low-cost flexible nanochannel can also be used in various applications, including DNA sequencing and biomimetic ion channel.
PubMed: 38511871
DOI: 10.1002/open.202400008 -
Pediatric Gastroenterology, Hepatology... Mar 2024Infantile hypertrophic pyloric stenosis (IHPS) is a common gastrointestinal disease in neonates and hypochloremia metabolic alkalosis is a typical laboratory finding in...
PURPOSE
Infantile hypertrophic pyloric stenosis (IHPS) is a common gastrointestinal disease in neonates and hypochloremia metabolic alkalosis is a typical laboratory finding in affected patients. This study aimed to analyze the clinical characteristics of infants with IHPS and evaluate the association of clinical and laboratory parameters with ultrasonographic findings.
METHODS
Infants diagnosed with IHPS between January 2017 and July 2022 were retrospectively evaluated.
RESULTS
A total of 67 patients were included in the study. The mean age at diagnosis was 40.5±19.59 days, and the mean symptom duration was 11.97±9.91 days. The mean pyloric muscle thickness and pyloric canal length were 4.87±1.05 mm and 19.6±3.46 mm, respectively. Hyponatremia and metabolic alkalosis were observed in five (7.5%) and 36 (53.7%) patients, respectively. Serum sodium (=0.011), potassium (=0.023), and chloride levels (=0.015) were significantly lower in patients with high bicarbonate levels (≥30 mmol/L). Furthermore, pyloric canal length was significantly higher in patients with high bicarbonate levels (=0.015). To assess metabolic alkalosis in IHPS patients, the area under the receiver operating characteristic curve of pyloric canal length was 0.910 and the optimal cutoff value of the pyloric canal length was 23.5 mm.
CONCLUSION
We found a close association between laboratory and ultrasonographic findings of IHPS. Clinicians should give special consideration to patients with pyloric lengths exceeding 23.5 mm and appropriate fluid rehydration should be given to these patients.
PubMed: 38510581
DOI: 10.5223/pghn.2024.27.2.88