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Cureus Feb 2024This comprehensive review explores the practice of fetal reduction through potassium chloride infusion in unruptured heterotopic pregnancies. Heterotopic pregnancies,... (Review)
Review
This comprehensive review explores the practice of fetal reduction through potassium chloride infusion in unruptured heterotopic pregnancies. Heterotopic pregnancies, characterized by the simultaneous occurrence of intrauterine and extrauterine gestations, present unique challenges in reproductive medicine. The review defines fetal reduction and underscores its significance in mitigating risks associated with heterotopic pregnancies, including the threat of rupture, maternal morbidity, and adverse outcomes. The analysis encompasses the background, methods, efficacy, ethical considerations, and future directions related to the procedure. Findings highlight the efficacy and safety of potassium chloride infusion, emphasizing the importance of proper patient selection and counseling. Implications for clinical practice underscore the procedure's viability in specific cases where the benefits outweigh the associated risks. The review concludes with recommendations for future studies, encouraging further research on procedural techniques, alternative methods, and the psychosocial impact on patients. This work is a foundation for advancing the management of unruptured heterotopic pregnancies, providing insights for clinicians and researchers to improve clinical outcomes and patient care.
PubMed: 38449926
DOI: 10.7759/cureus.53618 -
Frontiers in Medicine 2023Bartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of...
INTRODUCTION
Bartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce.
METHODS
We retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea.
RESULTS
All patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0-271) months, and their median follow-up was 8 (range, 0.5-27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had gene mutations, 1 had gene mutations, 33 had gene mutations, and 1 had mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, = 4; CKD G5, = 2].
CONCLUSION
BS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3-G5.
PubMed: 36993809
DOI: 10.3389/fmed.2023.1099840 -
Foods (Basel, Switzerland) Apr 2022cheese is obtained from whey proteins. The production of this cheese is the most economical way to recover and concentrate whey proteins, which is why it is frequently...
cheese is obtained from whey proteins. The production of this cheese is the most economical way to recover and concentrate whey proteins, which is why it is frequently made in some Latin American countries. Four cheese treatments were prepared with different concentrations and combinations of salts (sodium chloride and/or potassium chloride) and were conventionally or vacuum packed. Proteolysis, peptide concentration, angiotensin-converting enzyme (ACE) inhibitory and antioxidant (DPPH and ABTS) activities were evaluated over time (one, seven and fourteen days). cheese presented antioxidant and ACE inhibitory activities, however, these values vary depending on salt addition, type of packaging and time of storage. The highest values of antioxidant activity (ABTS) were found in cheese added with 1.5% NaCl and 1.5% (NaCl/KCl, 1:1). Cheese without added salt and vacuum packed presented the highest ACE inhibition percentage at day seven. Therefore, it can be concluded that cheese elaborated exclusively of sweet whey, presents antioxidant and ACE inhibition activity. However, for a cheese with ACE inhibitory capacity, it is recommended not to add salts or add at 1% (NaCl) and vacuum pack it. Additionally, for a cheese with antioxidant activity, it is recommended to add salt at 1.5% either NaCl or (1:1) NaCl/KCl and pack it either in a polyethylene bag or vacuum. In conclusion, cheese elaborate with 100% sweet whey is a dairy product with antioxidant and ACE inhibition activity, being low in salt and fat.
PubMed: 35563990
DOI: 10.3390/foods11091264 -
Experimental Biology and Medicine... Jul 2021Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study...
Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study examined if prenatal programming by maternal injection of dexamethasone on days 15 and 16 of gestation affected the blood pressure comparably in female and male offspring. Our hypothesis was that males would be affected by prenatal dexamethasone to a greater extent than females and that either an increase in renal tubular transporter abundance or an increase in renin or aldosterone system would be associated with hypertension with prenatal programming. Prenatal dexamethasone increased blood pressure at two months and six months of age and resulted in proteinuria and albuminuria at six months in male but not female rat offspring. There was no effect of prenatal dexamethasone on blood pressure and proteinuria at one month in male and in female offspring. While prenatal dexamethasone increased male renal thick ascending limb sodium potassium two chloride cotransporter protein abundance at two months, prenatal dexamethasone on days 15 and 16 of gestation did not affect transporter abundance in males at other ages, nor did it affect proximal tubule sodium/hydrogen exchanger or distal convoluted tubule sodium chloride cotransporter protein abundance at any age. There was no difference in systemic renin or aldosterone in the prenatal dexamethasone group compared to same sex controls. In conclusion, male but not female offspring have an increase in blood pressure and urinary protein excretion with prenatal dexamethasone. The increase in blood pressure with prenatal programming was not associated with a consistent increase in renal tubular transporter protein abundance, nor plasma renin activity and serum aldosterone.
Topics: Angiotensins; Animals; Dexamethasone; Female; Glucocorticoids; Hypertension; Kidney Tubules, Proximal; Male; Pregnancy; Prenatal Exposure Delayed Effects; Proteinuria; Rats; Rats, Sprague-Dawley; Renin; Sex Factors; Sodium-Hydrogen Exchangers; Sodium-Potassium-Chloride Symporters
PubMed: 33794700
DOI: 10.1177/15353702211003294 -
The American Journal of the Medical... Sep 2020The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial... (Review)
Review
The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g., IL-6 and TNFα), developing into a self-targeting, toxic "cytokine storm" causing critical pulmonary tissue damage. The need for a therapeutic that is available immediately is growing daily but the de novo development of a vaccine may take years. Therefore, repurposing of approved drugs offers a promising approach to address this urgent need. Inhaled furosemide, a small molecule capable of inhibiting IL-6 and TNFα, may be an agent capable of treating the Coronavirus Disease 2019 cytokine storm in both resource-rich and developing countries. Furosemide is a "repurpose-able" small molecule therapeutics, that is safe, easily synthesized, handled, and stored, and is available in reasonable quantities worldwide.
Topics: Administration, Inhalation; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Furosemide; Humans; Immunity, Innate; Inflammation Mediators; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 32622469
DOI: 10.1016/j.amjms.2020.05.044 -
Nature Neuroscience May 2024Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to...
Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.
Topics: Animals; Dendrites; Eukaryotic Initiation Factor-4G; Protein Biosynthesis; Neurons; Open Reading Frames; Rats; Mice; Cells, Cultured; Potassium Chloride
PubMed: 38589584
DOI: 10.1038/s41593-024-01615-5 -
The American Journal of Clinical... Jul 2021Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce...
BACKGROUND
Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce sodium intake.
OBJECTIVE
The purpose of this study was to quantitatively estimate changes in intakes of sodium and potassium by the US population assuming use of potassium-based NaCl replacers in top dietary sodium sources.
METHODS
Data collected in the What We Eat in America (WWEIA) component of the 2015-2016 and 2009-2010 NHANES were used to identify top-ranking sources of dietary sodium among the population aged 2 y and older based on contributions from food categories aligning with the FDA draft guidance for voluntary sodium reduction. Predicted nutrient intakes were estimated in models assuming total and feasible and practical (F&P) replacement of added NaCl with KCl in foods and ingredients within the top food sources of sodium. An expert elicitation was conducted to collect information on the F&P KCl replacement of added NaCl.
RESULTS
Using 2015-2016 consumption data, the total replacement of added NaCl with KCl in the 18 top-ranking sources of dietary sodium results in a predicted sodium intake of 2004 mg/d from the replacement of 1406 mg/d sodium with 1870 mg/d potassium as KCl. Modeled F&P replacement predicted sodium intakes of 3117 mg/d (range of 2953 to 3255 mg/d) from the replacement of 294 mg/d sodium (155 to 457 mg/d) with 390 mg/d potassium (206 to 608 mg/d). Similar results are seen with 2009-2010 data.
CONCLUSIONS
The F&P replacement of NaCl with KCl in top-ranking sources of dietary sodium modeled in this study can result in decreased sodium to a level consistent with the short-term intake goal targeted by the FDA of 3000 mg/d, with the mean potassium intake remaining in the range recommended for the apparently healthy population.
Topics: Cross-Sectional Studies; Food; Humans; Models, Biological; Nutrition Surveys; Potassium Chloride; Potassium, Dietary; Sodium, Dietary; United States
PubMed: 33755042
DOI: 10.1093/ajcn/nqab020 -
Brain : a Journal of Neurology Oct 2023Although the Na-K-Cl cotransporter (NKCC1) inhibitor bumetanide has prominent positive effects on the pathophysiology of many neurological disorders, the mechanism of...
Although the Na-K-Cl cotransporter (NKCC1) inhibitor bumetanide has prominent positive effects on the pathophysiology of many neurological disorders, the mechanism of action is obscure. Attention paid to elucidating the role of Nkcc1 has mainly been focused on neurons, but recent single cell mRNA sequencing analysis has demonstrated that the major cellular populations expressing NKCC1 in the cortex are non-neuronal. We used a combination of conditional transgenic animals, in vivo electrophysiology, two-photon imaging, cognitive behavioural tests and flow cytometry to investigate the role of Nkcc1 inhibition by bumetanide in a mouse model of controlled cortical impact (CCI). Here, we found that bumetanide rescues parvalbumin-positive interneurons by increasing interneuron-microglia contacts shortly after injury. The longitudinal phenotypic changes in microglia were significantly modified by bumetanide, including an increase in the expression of microglial-derived BDNF. These effects were accompanied by the prevention of CCI-induced decrease in hippocampal neurogenesis. Treatment with bumetanide during the first week post-CCI resulted in significant recovery of working and episodic memory as well as changes in theta band oscillations 1 month later. These results disclose a novel mechanism for the neuroprotective action of bumetanide mediated by an acceleration of microglial activation dynamics that leads to an increase in parvalbumin interneuron survival following CCI, possibly resulting from increased microglial BDNF expression and contact with interneurons. Salvage of interneurons may normalize ambient GABA, resulting in the preservation of adult neurogenesis processes as well as contributing to bumetanide-mediated improvement of cognitive performance.
Topics: Mice; Animals; Bumetanide; Sodium Potassium Chloride Symporter Inhibitors; Microglia; Brain-Derived Neurotrophic Factor; Parvalbumins; Solute Carrier Family 12, Member 2; Interneurons; Neurogenesis
PubMed: 37082944
DOI: 10.1093/brain/awad132 -
ELife Apr 2020Cation-chloride-cotransporters (CCCs) catalyze transport of Cl with K and/or Naacross cellular membranes. CCCs play roles in cellular volume regulation, neural...
Cation-chloride-cotransporters (CCCs) catalyze transport of Cl with K and/or Naacross cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the K-Cl cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K and Cl ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family.
Topics: Animals; Binding Sites; Cryoelectron Microscopy; Liposomes; Mice; Nanoparticles; Protein Conformation; Structure-Activity Relationship; Symporters
PubMed: 32286222
DOI: 10.7554/eLife.52505 -
Frontiers in Cell and Developmental... 2021Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production...
Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production is negligible, water flow in and out of the cell determines the cell volume variation. Water flux follows hydraulic and osmotic gradients; the latter is generated by various ion channels, transporters, and pumps in the cell membrane. Compared to the widely studied roles of sodium, potassium, and chloride in cell volume regulation, the effects of proton and bicarbonate are less understood. In this work, we use mathematical models to analyze how proton and bicarbonate, combined with sodium, potassium, chloride, and buffer species, regulate cell volume upon inhibition of ion channels, transporters, and pumps. The model includes several common, widely expressed ion transporters and focuses on obtaining generic outcomes. Results show that the intracellular osmolarity remains almost constant before and after cell volume change. The steady-state cell volume does not depend on water permeability. In addition, to ensure the stability of cell volume and ion concentrations, cells need to develop redundant mechanisms to maintain homeostasis, i.e., multiple ion channels or transporters are involved in the flux of the same ion species. These results provide insights for molecular mechanisms of cell volume regulation with additional implications for water-driven cell migration.
PubMed: 34249935
DOI: 10.3389/fcell.2021.683686