Potassium Chloride Research Articles

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-β on reno-renal reflexes in anaesthetised rats.

Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1β modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves. In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1β (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin. The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1β infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1β, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1β, by almost 80% below vehicle, again without effect on either MAP or HR. The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1β. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.

Catalytic strategies for uniform monolayer MoSe2 growth in CVD processes

To facilitate the widespread utilization of devices based on two-dimensional transition metal dichalcogenide (TMDC) materials, addressing the challenge of producing large-area and uniform monolayers is crucial. In this study, we investigated the efficacy of various catalysts in promoting the growth of monolayer MoSe2 through chemical vapor deposition (CVD) as a potential solution to improve surface coverage and uniformity while maintaining the monolayer structure. Five distinct water-soluble catalysts (sodium chloride (NaCl), zinc chloride (ZnCl2), potassium hydroxide (KOH), potassium chloride (KCl), potassium oxalate (K2C2O4)) were employed in conjunction with a glass substrate for the CVD-based growth of monolayer MoSe2. We applied these catalyst solutions as thin layers onto SiO2/Si substrates to observe their specific catalytic effects on monolayer MoSe2 formation. MoSe2 was selected as the target material due to its promising characteristics within the TMDC family, particularly its high mobility. Our findings revealed that NaCl, ZnCl2, KCl, and K2C2O4 catalysts enhanced monolayer growth in the 2H phase on SiO2/Si substrates, while the glass substrate resulted in a hybrid 1T/2H MoSe2 structure, albeit with the highest surface coverage. Furthermore, the use of a catalyst allowed us to bypass the laborious transfer step by enabling direct growth of the MoSe2 flakes on the Si/SiO2 substrate, eliminating the risk of flake damage arising from the transfer process. Among the catalyst solutions, NaCl yielded the most homogeneous MoSe2 monolayer growth with relatively high coverage.

A Comparative Study of Fertilizer Prices Purchased by Farmers from Rythu Bharosa Kendras (RBKs) and Other Agencies in Andhra Pradesh

Rythu Bharosa Kendras - a one stop solutions for all agriculture & allied issues, was launched by state government of Andhra Pradesh in 2020. It addresses various issues and provide services to the farmers at the village level. Fertilizers are one among the services offered at Rythu Bharosa Kendras. The current study was carried out during the year 2022 and 2023 to find any significant variation in the average price of the fertilizers purchased by the farmers from Rythu Bharosa Kendras versus other agencies in Tirupati and Chittoor districts of Andhra Pradesh. A representative sample of 120 farmers in two districts of Andhra Pradesh i.e., Tirupati and Chittoor were selected for the study. Through a pre-structed interview schedule, prices of fertilizers purchased by the farmers from Rythu Bharosa Kendras vs other agencies were collected. In the study area, other agencies from where farmers purchased fertilizers included private fertilizer wholesalers, retailers, fellow farmers, non-institutional financers, etc. To study the average price comparison, the set of fertilizers that were commonly purchased at Rythu Bharosa Kendras and other agencies were selected. They were Urea, Diammonium phosphate (DAP), Muriate of Potash (MOP), N20:P20:K0:S13 (N:P:K:S fertilizer grade), N10:P26:K26 (N:P:K fertilizer grade). From the data collected and through descriptive statistical analysis it was clear that for all the common fertilizers the average amount of fertilizer per bag at Rythu Bharosa Kendras was comparatively lower than that of fertilizers purchased at other agencies. The average price variation of fertilizer per bag at Rythu Bharosa Kendras to other agencies for Urea, DAP, MOP, N20:P20:K0:S13 grade, N10:P26:K26 grade were Rs. 27.5, Rs. 40, Rs. 33, Rs. 44 & Rs. 92 with a variation in percentage by 10.3%, 2.96%, 2.84%, 3.26% & 6.31% respectively. By ensuring the prompt availability of required set of fertilizers in line with the cropping pattern of the farmers and by streamlining the supply chain aspects of fertilizes, especially from fertilizers hub to Rythu Bharosa Kendras, will be beneficial & results in cost optimization to the farmers.

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

Monte Carlo simulation study of the structure of calcium and potassium chlorides ternary solutions

ABSTRACT Monte Carlo simulations were conducted on pure water and aqueous calciumand potassium chloride ternary solutions at different salts concentrations. To assess the local order within the solutions, the Monte Carlo simulations utilised the Madrid-2019 force field, usingtheTIP4P/2005 water model and scaled charges. The results demonstrate that as the salt concentrations increase, there is a notable decrease in the contribution of the structured tetrahedral arrangement of water molecules, favouring an unstructured configuration instead. The use of the nearest neighbour approach, provided unambiguous information regarding the radial and orientation characteristics of the unstructured configuration of water. Structures of the solvation shells around ions are also studied. The Monte Carlo simulations indicate that as the salt concentration increases, the hydration number around the cation decreases. This effect is likely due to the occasional substitution of some water molecules in the first hydration shell by chlorine ions.

Laboratory investigation on inhibition of polyvinyl alcohol used for wireline coring drilling

AbstractTo address the problems of wall collapse, cuttings slurrying, and scaling on the inner wall of the drill pipe, which often occur in small-diameter diamond wireline core drilling, the inhibition properties of polyvinyl alcohol (PVA) was investigated, and the formulation of solids-free drilling fluid with PVA as the inhibitor were completed. PVA has the advantages of fast adsorption and easy regulation of rheological properties Firstly the inhibition effect of PVA was compared with that of common inorganic salts (sodium chloride, NaCl, potassium chloride, KCl) by bentonite dispersion test, linear swelling test, shale rolling recovery test and mud ball immersion test in this study. Then, the inhibition mechanism of PVA was analyzed with potentiometric particle size tests, Fourier transform infrared (FT-IR) and X-ray Diffraction (XRD) measurements. Based on the outstanding inhibition performance of PVA, tackifiers and filtration reducers were preferred through the compatibility test. And finally, the effects of various contaminants on the comprehensive performance of the formulated solids-free drilling fluids were evaluated. The results showed that PVA exhibited better inhibition of clay hydration and dispersion in shale recovery and linear swelling compared to NaCl and KCl, which was particularly evident in the mud ball immersion test. FT-IR and XRD tests revealed that the inorganic salts were used to replace the cations with larger radius and high degree of hydration in the clay layer by ion exchange ti achieve the effect of clay de-watering by reducing the spacing of the clay interlayer and the electrostatic repulsion between the particles. However, PVA is strongly adsorbed on the clay surface in the form of hydrogen bonds due to its unique multi-hydroxyl chain structure, forming a hydrophobic barrier to prevent water molecules from entering the clay layer, thus inhibiting the hydration and swelling of the clay. Using PVA as an inhibitor, compounded with xanthan gum, sulfonated lignite resin and sulfonated gilsonite (FT-1), the solids-free drilling fluid is promising for use in diamond wireline core drilling in complex formations.

Influence of Carboxymethyl Cellulose as a Thickening Agent for Glauber's Salt-Based Low Temperature PCM.

This work is focused on a novel, promising low temperature phase change material (PCM), based on the eutectic Glauber's salt composition. To allow phase transition within the refrigeration range of temperatures of +5 °C to +12 °C, combined with a high repeatability of melting-freezing processes, and minimized subcooling, the application of three variants of sodium carboxymethyl cellulose (Na-CMC) with distinct molecular weights (700,000, 250,000, and 90,000) is considered. The primary objective is to optimize the stabilization of this eutectic PCM formulation, while maintaining the desired enthalpy level. Preparation methods are refined to ensure repeatability in mixing components, thereby optimizing performance and stability. Additionally, the influence of Na-CMC molecular weight on stabilization is examined through differential scanning calorimetry (DSC), T-history, and rheology tests. The PCM formulation of interest builds upon prior research in which borax, ammonium chloride, and potassium chloride were used as additives to sodium sulfate decahydrate (Glauber's salt), prioritizing environmentally responsible materials. The results reveal that CMC with molecular weights of 250 kg/mol and 90 kg/mol effectively stabilize the PCM without phase separation issues, slowing crystallization kinetics. Conversely, CMC of 700 kg/mol proved ineffective due to the disruption of gel formation at its low gel point, hindering higher concentrations. Calculations of ionic concentration indicate higher Na ion content in PCM stabilized with 90 kg/mol CMC, suggesting increased ionic interactions and gel strength. A tradeoff is discovered between the faster crystallization in lower molecular weight CMC and the higher concentration required, which increases the amount of inert material that does not participate in the phase transition. After thermal cycling, the best formulation had a latent heat of 130 J/g with no supercooling, demonstrating excellent performance. This work advances PCM's reliability as a thermal energy storage solution for diverse applications and highlights the complex relationship between Na-CMC molecular weight and PCM stabilization.

Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.

Immunological isolation and characterization of neuronal progenitors from human dental pulp: A laboratory-based investigation.

Dental pulp stem cells (DPSCs) contain a population of stem cells with a broad range of differentiation potentials, as well as more lineage-committed progenitors. Such heterogeneity is a significant obstacle to experimental and clinical applications. The aim of this study is to isolate and characterize a homogenous neuronal progenitor cell population from human DPSCs. Polysialylated-neural cell adhesion molecule (PSA-NCAM+) neural progenitors were isolated from the dental pulp of three independent donors using magnetic-activated cell sorting (MACS) technology. Immunofluorescent staining with a panel of neural and non-neural markers was used to characterize the magnetically isolated PSA-NCAM+ fraction. PSA-NCAM+ cells were then cultured in Neurobasal A supplemented with neurotrophic factors: dibutyryl cyclic-AMP, neurotrophin-3, B27 and N2 supplements to induce neuronal differentiation. Both PSA-NCAM+ and differentiated PSA-NCAM+ cells were used in Ca2+ imaging studies to assess the functionality of P2X3 receptors as well as membrane depolarization. PSA-NCAM+ neural progenitors were isolated from a heterogeneous population of hDPSCs using magnetic-activated cell sorting and anti-PSA-NCAM MicroBeads. Flow cytometry analysis demonstrated that immunomagnetic sorting significantly increased the purity of PSA-NCAM+ cells. Immunofluorescent staining revealed expression of pan-neuronal and mature neuronal markers, PGP9.5 and MAP2, respectively, as well as weak expression of the mature sensory markers, peripherin and islet1. ATP-induced response was mediated predominately by P2X3 receptors in both undifferentiated and differentiated cells, with a greater magnitude observed in the latter. In addition, membrane depolarizations were also detected in cells before and after differentiation when loaded with fast-voltage-responding fluorescent molecule, FluoVolt™ in response to potassium chloride. Interestingly, only differentiated PSA-NCAM+ cells were capable of spontaneous membrane oscillations. In summary, DPSCs contain a population of neuronal progenitors with enhanced neural differentiation and functional neural-like properties that can be effectively isolated with magnetic-activated cell sorting (MACS).

Analysis of swimming trajectories in Daphnia similis as an environmental impact assessment tool

Analysis of swimming trajectories in <i>Daphnia similis</i> as an environmental impact assessment tool

Congenital chloride diarrhoea in a Chinese infant with a compound heterozygous SLC26A3 mutation

IntroductionCongenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations.Case presentationA 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency.ConclusionsCCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

Ketamine-induced prevention of SD-associated late infarct progression in experimental ischemia

Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.

Exploring the role of hydrophobic nanofluids in reducing shale swelling during drilling: A step towards eco-friendly and sustainable practices

This study conducts a comparative analysis between hydrophobic nanosilica (HNS) and potassium chloride (KCl), a widely used shale inhibitor, to better understand how HNS can effectively manage water and shale interactions by restricting mud filtration into the formation. Due to their small size and optimal interfacial properties, nanoparticles emerge as remarkable solutions for addressing this issue. In this work, shale samples were collected from the Kolosh Formation in the Kurdistan Region of Iraq, known for being one of the most challenging formations to drill. Investigations into the properties of drilling fluid were conducted using low pressure and low temperature (LPLT) and high pressure high temperature (HPHT) filter press, alongside analyzing rheological properties at three different temperatures (25, 50 and 75°C). In addition, the impact of the HNS on clay swelling was examined using the liner swelling meter (LSM) test, shale dispersion test (SDT) and capillary suction time (CST) test. The obtaining results revealed that the shale hydration in the drilling fluids was reduced 24.36–15.53% and the shale recovery at high temperatures was improved from 80.2% to 94% by adding 0.4 wt% HNS. Furthermore, HNS demonstrated improved clay suspension in the CST test wherein the suspension time reduced from 303 to 80 sec at the same HNS concentration. Utilizing HNS effectively reduced clay swelling in all experiments and enhanced the rheological properties of the mud, showcasing stability across a range of temperatures and significantly reducing the formation of filter cake and fluid loss. As is obvious, KCl based drilling fluids are prohibited in several parts in the word due to its negative impact on the environment and subsurface activities; thus, it can be substituted by HNS as an active shale inhibitor additive.

Evaluation of serum electrolyte abnormalities in type II diabetic patients presenting in Gulab Devi hospital, Lahore

Background: The hallmark of diabetes mellitus (DM) is hyperglycemia brought on by an absolute or relative insulin shortage. Globally, the prevalence of DM is a major cause for worry. The International Diabetes Federation estimates that 26.7% of Pakistan's adult population would have diabetes in 2022, totalling over 33,000,000 cases 1. Patients with diabetes are more likely to experience electrolyte imbalances, which may be caused by an imbalance in the distribution of electrolytes. Electrolytes play a vital role in the maintenance of blood acid-base balance, composition of body fluids, blood clotting, muscle and nerve conduction. Impaired electrolytes balance in diabetics may lead to micro and macrovascular complications. Aims and objectives: The objective of this study is to investigate disturbances in serum electrolytes including Sodium (Na+), Potassium (K+) and Chloride (Cl) in Type II diabetics. Methodology: This has been a descriptive cross-sectional study where random sampling technique was used. 3cc clotted blood samples of 100 Type II diabetic patients were collected from diabetic OPD and medicine wards of Gulab Devi Chest Hospital Lahore and processed in the Pathology lab of Gulab Devi Educational Complex. Results: Out of 100 samples of type II diabetic patients, there were 65 patients in which serum sodium levels were decreased. Serum potassium and serum chloride were slightly increased in some patients. Conclusion: In this study, serum sodium levels were significantly decreased in type II diabetic patients, while no significant alteration was observed in serum potassium and chloride levels. Serum electrolytes should be routinely measured in diabetics to prevent complications.

Fibulin-5 Is Required for Small Artery Development and Function

Introduction: Fibulins are a family of eight extracellular matrix proteins with diverse functions. Fibulin-4 and -5 (FBLN-4 and -5), in particular, have been shown to be important for elastic fiber assembly. Mutations in each of the genes lead to cutis laxa, a syndrome characterized by loose skin with variable organ involvement, particularly in the vasculature, lungs and skeleton. We recently characterized a mouse model carrying a disease-causing mutation in Fbln4 (E57K) and, contrary to conduit arteries that had elastic fiber fragmentation and stiffness, Fbln4E57K resistance arteries were structurally intact. Functionally however, Fbln4E57K mesenteric arteries exhibited endothelial dysfunction secondary to increased shear stress from large artery stiffness. Loss of FBLN5 has been shown to lead to elastic fiber fragmentation in conduit arteries, but the consequences of its loss on resistance arteries are unknown. Therefore, the objectives of this study were to determine the structural and functional consequences of FBLN5 loss on resistance arteries. Methods: We utilized adult Fbln5 knock-out (KO) mice and examined the ultrastructure of renal and mesenteric arteries via transmission electron microscopy. Functionally, using pressure myography, we characterized the myogenic tone and reactivity of Fbln5 KO and littermate control third-order mesenteric arteries to various vasoactive substances including acetylcholine, papaverine, angiotensin II, phenylephrine and potassium chloride. Results: While the internal elastic lamina (IEL) of Fbln5KO mice resistance arteries was largely intact, the external elastic lamina (EEL) was nearly absent. Similar to Fbln4E57K mice, Fbln5KO mesenteric arteries exhibited impaired endothelial-dependent vasorelaxation, likely secondary to proximal large artery stiffness. Unlike Fbln4E57K mesenteric arteries however, Fbln5 KO mesenteric arteries exhibited increased myogenic tone as well as a hypercontractile response to angiotensin II and potassium chloride, but not to phenylephrine. Conclusions: In addition to highlighting differences in the requirements for elastic fiber assembly along the arterial tree, these data emphasize the differential contribution of FBLN4 and FBLN5 to IEL vs. EEL in resistance arteries and suggest pathway-specific changes in smooth muscle cell contractility secondary to FBLN5 deficiency. This work was supported by the Washington University Pediatric Nephrology Research Core Pilot Grant Program to CMH. Funds were also provided by The Department of Pediatrics at Washington University in St. Louis School of Medicine to CMH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

ObjectiveTo investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) and erectile function in diabetic rats. MethodsStreptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction of CC induced by potassium chloride, phenylephrine, and Nω-Nitro-L-arginine methyl ester and relaxation of CC induced by electric field stimulation (EFS) and sodium nitroprusside (SNP) (endothelium-dependent and endothelium-independent stimuli, respectively), and Y-27632 (Rho-kinase inhibitor) were examined in organ baths. Direct contraction or relaxation induced by palosuran and urotensin-II (U-II) were also evaluated. Expressions of nitric oxide synthetase (NOS) enzymes, RhoA, oxidative stress regulators, and U-II were analyzed by Western blotting or immunohistochemisty. ResultsInduction of diabetes in rats resulted in decreased relaxant response to SNP, decreased pD2 value of SNP, attenuated relaxant response to Y-27632 as well as the decreased RhoA expression in CC. Palosuran treatment of diabetic rats reversed all of these parameters; however, it further impaired the already weakened relaxation of diabetic CC in response to EFS. Although induction of diabetes did not change U-II expression in CC significantly, palosuran treatment reduced U-II expression in diabetic CC. The expression level of nNOS was lowered in diabetic CC; however palosuran treatment did not change the decreased nNOS expression. In vitro exposure of diabetic CC strips to palosuran produced a direct relaxant response. ConclusionPalosuran treatment did not affect the expression of NOS enzymes or reduced nitrergic conduction induced by EFS stimulation in diabetic CC. However, while directly triggering a relaxant response, it did not induce a prominent contraction either by decreasing U-II expression, or increasing the sensitivity of CC to NO which suggested that palosuran has the potential to support erectile function. Further and comprehensive studies are required to clarify this issue.

Stronger vasoconstriction and weaker vasodilation in mesenteric arteries of Ossabaw than Göttingen minipigs before manifestation of metabolic syndrome

The metabolic syndrome predisposes and contributes to the development and progression of atherosclerosis. The minipig strain “Ossabaw” is characterized by a polygenic predisposition to develop metabolic syndrome and diffuse atherosclerosis in response to a hypercaloric atherogenic diet. The aim of this study was to investigate whether Ossabaw minipigs exhibit an altered vasomotor function even before they develop their diseased phenotype. Mesenteric arteries of adult Ossabaw (n=30) and Göttingen minipigs (n=40), a pig strain without genetic predisposition to a metabolic syndrome, were harvested postmortem, dissected, and mounted on a myograph for isometric force measurements. Maximal vasoconstriction to smooth muscle cell depolarization with potassium chloride (KClmax) was repeatedly induced (twice 0.6×10−1 mol/L and twice 1.2×10−1 mol/L). Cumulative concentration-response curves were determined in response to 1×10−9 -1×10−4 mol/L norepinephrine. Endothelium-dependent and -independent vasodilation were analyzed in response to carbachol and nitroprusside, respectively (1×10−9 - 1×10−4 mol/L, each) after pre-constriction by norepinephrine. The baseline diameter of mesenteric arteries from Ossabaw minipigs was smaller than that from Göttingen minipigs (329±20 vs. 435±11 μm), and mesenteric arteries of Ossabaw minipigs developed a higher baseline force of contraction than mesenteric arteries of Göttingen minipigs (6.2±0.7 vs. 3.6±0.3 mN). The maximal vasoconstrictor response to KCl was comparable between the minipig strains. Vasoconstriction in response to norepinephrine was more pronounced in Ossabaw than in Göttingen minipigs (143±9 vs. 108±6% KClmax). Endothelium-dependent vasodilation (46.4±5.5 vs. 16.0±3.0% of norepinephrine-induced preconstriction) and -independent vasodilation (36.7±4.9 vs. 2.3±0.6% of norepinephrine-induced preconstriction) were less pronounced in Ossabaw than in Göttingen minipigs. Neither the differences in baseline diameter nor in baseline developed force of contraction had any effect on the above data, as analyzed in retrospectively matched subsets of mesenteric arteries with a comparable baseline diameter or a comparable baseline developed force of contraction, respectively. Even before the development of metabolic syndrome, vasomotor function is shifted to more vasoconstriction and less vasodilation in Ossabaw minipigs, suggesting a genetic predisposition for the early development of vascular dysfunction. Thus, Ossabaw minipigs may be a suitable model to reflect the human situation of a heterogeneous, genetically determined primordial risk constellation for vascular dysfunction. This work was supported by the German Research Foundation [SFB 1116 B08 to G.H. and P.K.] and the European COST ACTION in CARDIOPROTECTION [CA16225 to G.H. and IG16225 to G.H. and P.K.]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: which dose is more suitable?

Cisplatin is a widely used and potent cytotoxic chemotherapy agent, but its nephrotoxicity is a significant limiting side effect. Various premedication approaches have been implemented to preserve renal function, including magnesium (Mg) preloading. However, the optimal Mg dosage is still unknown. Our study aimed to assess the protective effects of different Mg doses as premedication in cisplatin-based chemoradiotherapy for patients with local/locally advanced cervical and head-neck cancers. This retrospective, multicenter study involved premedication with saline infusion containing potassium chloride and magnesium sulfate (MgSO4) for all patients before cisplatin treatment. Patients were divided into two groups: 12 mEq MgSO4 (low-dose Mg preload group, low-Mg) and 24 mEq MgSO4 (high-dose Mg preload group, high-Mg). Renal function was evaluated using serum creatinine (sCr, mg/dl) and estimated glomerular filtration rate (eGFR, ml/min). Acute kidney injury (AKI) was defined per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Renal outcomes and efficacy were compared between the groups. In the low-Mg group (n = 159), sCr levels were significantly higher compared to baseline, various weeks during treatment, and at the 1st, 3rd, 6th, and 12th months post-treatment (p < 0.001). In the high-Mg group (n = 128), no significant changes were observed during treatment and at 1st, 3rd, and 12th months post-treatment (p > 0.05). A significant reduction in mean sCr level from baseline to 6 months was noted in the high-Mg group (p < 0.001). eGFR values are generally correlated with sCr levels. AKI occurred in 21 (13.2%) and 22 (17.7%) patients in the low-Mg and high-Mg groups, respectively (p = 0.292). There was no difference in progression-free or overall survival between the groups. We clearly demonstrated that saline hydration with 24 mEql MgSO4 supplementation before cisplatin treatment has a better renal protective effect than 12 mEql MgSO4 without reducing efficacy, especially in patients with local/local advanced cervical and head-neck cancer receiving cisplatin with concurrent radiotherapy.

A novel preclinical model of fentanyl-induced cardiorespiratory collapse to investigate resuscitation outcomes

Introduction: Opioid-related morbidities have become a critical public health concern, with ultrapotent synthetic opioids (UPSO) such as fentanyl contributing to the rise in opioid-related fatalities. Respiratory depression is the cardinal trait of fentanyl overdose, leading to systemic hypoxia and subsequent cardiorespiratory collapse (CRC). There is growing recognition that fentanyl induced CRC (fiCRC) is unique from other forms of sudden CRC. Yet, the consequences of fiCRC and its reversal remain poorly understood. This is due in part to the limited preclinical studies investigating rescue from fiCRC. Objective: using a novel model of fiCRC and subsequent reversal, this ongoing study aims to define the impact of UPSO and naloxone rescue on in vivo survival outcomes. Methods and Results: Male and female C57BL/6J mice were used. UPSO fentanyl i.v. administration (30 to 500 mcg/kg) suppressed breathing and subsequently led to fiCRC. The return of spontaneous circulation (ROSC) was achieved by performing manual chest compressions in combination of epinephrine administration after 8 minutes of fiCRC. In subset of mice, naloxone was administered post ROSC. Outcomes after 72 hours were accessed. The latency of fiCRC (mean arterial pressure at 40 mmHg) exhibited a negative correlation with the doses of fentanyl administered. Resuscitation from fiCRC was unreliable across the dose spectrum, while naloxone consistently rescued the majority of fiCRC animals. Naloxone increased ROSC rate from 54% to 86% when the dose of fentanyl was 30 mcg/Kg (n=22). With naloxone rescue, we compared fiCRC with non-opioid-induced cardiac arrest followed by potassium chloride injection (0.8 mg/g). Both models showed severe lung edema as evidenced by Evans Blue staining. However, the lung wet/dry weight ratio was higher in fiCRC group than in the non-opioid treatment group (5.50±0.05 vs. 6.60±0.60, n=4, p&lt;0.05). Survival in fiCRC group was significantly worse than in non-opioid treatment group (survival rate: 25% vs. 83%, n=17, p&lt;0.05). Conclusions: Our study highlights two important findings. First, the reliable resuscitation of fiCRC necessitates the use of naloxone. Second, the likelihood of injury is significant following successful rescue from fiCRC by naloxone. Our continued work using this fiCRC model will lead to insights that can be leveraged for strategies to mitigate injury and improve survival following fentanyl overdose. R01 HL163965 &amp; R01 DA057767. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Focal brain cooling suppresses spreading depolarization and reduces endothelial nitric oxide synthase expression in rats

This study aimed to investigate the effects of focal brain cooling (FBC) on spreading depolarization (SD), which is associated with several neurological disorders. Although it has been studied from various aspects, no medication has been developed that can effectively control SD. As FBC can reduce neuronal damage and promote functional recovery in pathological conditions such as epilepsy, cerebral ischemia, and traumatic brain injury, it may also potentially suppress the onset and progression of SD.We created an experimental rat model of SD by administering 1M potassium chloride (KCl) to the cortical surface. Changes in neuronal and vascular modalities were evaluated using multimodal recording, which simultaneously recorded brain temperature (BrT), wide range electrocorticogram, and two-dimensional cerebral blood flow. The rats were divided into two groups (cooling [CL] and non-cooling [NC]). Warm or cold saline was perfused on the surface of one hemisphere to maintain BrT at 37°C or 15°C in the NC and CL groups, respectively. Western blot analysis was performed to determine the effects of FBC on endothelial nitric oxide synthase (eNOS) expression.In the NC group, KCl administration triggered repetitive SDs (mean frequency = 11.57/h). In the CL group, FBC increased the duration of all KCl-induced events and gradually reduced their frequency. Additionally, eNOS expression decreased in the cooled brain regions compared to the non-cooled contralateral hemisphere.The results obtained by multimodal recording suggest that FBC suppresses SD and decreases eNOS expression. This study may contribute to developing new treatments for SD and related neurological disorders.