Role of Preservation Solution in Human Aneurysmatic Aorta Harvest and Transport: A Comparative Analysis of Different Solutions for Tissue Injury Protection.

INTRODUCTION: Human aortic tissues in vitro are tools to clarify the pathophysiological mechanisms of the cardiovascular system, cell culture, and transplants. Therefore, this study aims to analyze and compare the preservation of human aneurysmatic aortic tissues in three different solutions. METHODS: Six human abdominal aortic aneurysms were obtained from patients after surgical ablation. The aorta samples were incubated in different solutions - 0.9% normal physiological saline solution, Ringer's lactate solution, and histidine-tryptophan-ketoglutarate solution (Custodiol®). Segments were collected at 0, 6, 24, and 48 hours. Creatine kinase and nitrate/nitrite were quantified for each incubation time. The tissue's alpha-smooth muscle actin was analyzed by immunofluorescence. RESULTS: There was a significant increase in creatine kinase formation in the normal saline group at 0 and 48 hours and in the Ringer's lactate group at 0 and 48 hours (P=0.018 and P=0.028). The lower levels of creatine kinase and nitrate/nitrite and the aortic tissues' morphological integrity show that histidine-tryptophan-ketoglutarate has better tissue protection. These data suggest that histidine-tryptophan-ketoglutarate induces a protective effect on smooth muscle cells, with less tissue depletion in the aortic aneurysm. CONCLUSION: This study compared three preservation solutions with the potential for human abdominal aortic aneurysm tissue preservation. The histidine-tryptophan-ketoglutarate solution reduced tissue injury and improved tissue preservation in human abdominal aortic aneurysm tissue samples.

Histidine-trytophan-ketoglutarate cardioplegia reduces inflammatory response and serum levels of myocardial enzymes in newly developed right-thoracotomy rat model.

The objective of this research was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation that is both practical and economical and simulates clinical cardiac surgery. Concurrently, the study aimed to evaluate the myocardial protective effects conferred by histidine-tryptophan-ketoglutarate (HTK) cardioplegia. Thirty rats were randomly assigned to three groups: the histidine-tryptophan-ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of one hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional two hours. Following this observation period, the heart and blood samples were procured for subsequent analysis. During CPB, the average hematocrit level was significantly below the typical physiological range (P < 0.001). Histopathological scores were notably lower in the HTK group in contrast to the BC group (P < 0.001) or the DN group (P < 0.001). At 2 h after weaning off CPB, the levels of CK and CKMB in the DN and BC groups were notably elevated compared to the HTK group (P < 0.001). The levels of IL-6 and TNF-α proteins were notably increased in all three groups (P < 0.001), with the BC and DN groups showing higher increases compared to the HTK group (P < 0.001). This compact animal model of cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation might allow for both the study of myocardial ischemia-reperfusion injury as well as cardioprotective strategies. HTK cardioplegia could reduce inflammatory response and serum levels of myocardial enzymes in this newly developed right thoracotomy rat model.

Investigating Different Dynamic pHP1α States in Their KCl-Mediated Liquid-Liquid Phase Separation (LLPS) Using Solid-State NMR (SSNMR) and Molecular Dynamic (MD) Simulations.

Chromatin phase separation is dynamically regulated by many factors, such as post-translational modifications and effector proteins, and plays a critical role in genomic activities. The liquid-liquid phase separation (LLPS) of chromatin and/or effector proteins has been observed both in vitro and in vivo. However, the underlying mechanisms are largely unknown, and elucidating the physicochemical properties of the phase-separated complexes remains technically challenging. In this study, we detected dynamic, viscous, and intermediate components within the phosphorylated heterochromatin protein 1α (pHP1α) phase-separated system by using modified solid-state NMR (SSNMR) pulse sequences. The basis of these sequences relies on the different time scale of motion detected by heteronuclear Overhauser effect (hetNOE), scalar coupling-based, and dipolar coupling-based transfer schemes in NMR. In comparison to commonly utilized scalar coupling-based methods for studying the dynamic components in phase-separated systems, hetNOE offers more direct insight into molecular dynamics. NMR signals from the three different states in the protein gel were selectively excited and individually studied. Combined with molecular dynamics (MD) simulations, our findings indicate that at low KCl concentration (30 mM), the protein gel displays reduced molecular motion. Conversely, an increase in molecular motion was observed at a high KCl concentration (150 mM), which we attribute to the resultant intermolecular electrostatic interactions regulated by KCl.

Hypokalemia Induced Partial Nephrogenic Diabetes Insipidus: A Case Report.

ABSTRACT: Diabetes insipidus is a condition characterised by a large volume of diluted urine production and increased thirst. In this case report, a 49-year-old gentleman presented with 3 months of polyuria and polydipsia. He had a repeated history of hypokalemia. On the evaluation of polyuria and polydipsia, he was diagnosed with partial nephrogenic diabetes insipidus based on his inability to concentrate urine after a water deprivation test and his less than 50% response to exogenous desmopressin. On the evaluation of recurrent hypokalemia, the investigation reports met biochemical criteria for the diagnosis of Gitelman syndrome. He was encouraged to increase his fluid intake as required, and potassium chloride supplementation relieved his symptoms. This case report demonstrates the reversibility of nephrogenic diabetes insipidus with a correction of hypokalemia.

Comparison of routine del Nido cardioplegia vs two types of modified del Nido cardioplegias for myocardial protection among patients undergoing coronary artery bypass grafting (CABG) surgeries: A randomized double-blind clinical trial.

BACKGROUND: The del Nido cardioplegia solution is a widely used method for myocardial protection in various settings. However, there is limited evidence of its effectiveness in adult cardiac surgery, and the baseline solution, Plasma Lyte A, is not readily available, leading to the use of alternative baseline solutions. This study aims to investigate the effectiveness of routine del Nido cardioplegia in adult cardiac surgery and the impact of different baseline solutions on myocardial protection and other perioperative outcomes. METHODS: This study was a prospective, double-blind randomized parallel group clinical trial conducted at a single tertiary care hospital in Iran. A total of 187 adult patients were evaluated for eligibility, of which 120 met the inclusion criteria for elective isolated CABG surgery. The patients were randomly assigned to three groups, with each group consisting of 40 patients. The control group received a normal saline-based routine del Nido cardioplegia, Intervention Group A received Ringer lactate-based del Nido cardioplegia, and Intervention Group B received plain Ringer-based del Nido cardioplegia. The levels of Creatine Kinase-MB (CK-MB), Troponin T, Troponin I, and lactate were primarily assessed at four different times: after anesthesia induction (Baseline), 2 h, 12 h, and 24 h. RESULTS: Preoperative demographic and clinical characteristics were the same among groups with insignificant differences (p > 0.05). There was no significant difference among groups based on CK-MB, Troponin T, Troponin I, and lactate levels (p = 0.078, 0.143, 0.311, and 0.129 respectively). However, there was a significant difference in the time effect of Troponin T and Lactate (p = 0.034, p = <0.001). CONCLUSION: Normal saline, Ringer lactate, and plain Ringer provide comparable myocardial protection in adult-isolated CABG surgery with modified del Nido cardioplegia. Larger studies are needed to identify the best alternative to Plasma Lyte A while maintaining del Nido cardioplegia as the control.

Mitigating Cold Ischemic Injury: HTK, UW and IGL-2 Solution's Role in Enhancing Antioxidant Defence and Reducing Inflammation in Steatotic Livers.

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.

The Impact of Adding a Cationic Metal Salt and Curcumin to Monoammonium Glycyrrhizic Acid on Its Solubilizing Capacity and Gelation.

Monoammonium glycyrrhizic acid (MAG), a glycyrrhizic acid monoammonium salt, is a naturally derived low-molecular-weight gelling agent with surface-active properties. It has the capacity to individually facilitate the preparation of gel-solubilized drugs. As MAG is an anionic surfactant with carboxyl groups, the addition of counterions may affect micelle formation and gelation. In this study, the solubilization and gelling properties of MAG were investigated following the addition of metal salts (NaCl and KCl). The addition of metal salts resulted in a decrease in the critical micelle concentration and an increase in gel hardness. Supersaturation of curcumin (CUR) was maintained by the addition of metal salts because of increased micelle number and viscosity. When the gel hardness was compared between formulations with and without CUR, a significant reduction in hardness was observed with the solubilization of CUR. The addition of KCl prevented the decrease in the hardness of gels containing CUR compared to the addition of NaCl. Put together, the addition of metal salts had a noteworthy impact on micelle and gel formation of MAG. In particular, the addition of KCl was more effective in the preparation of gel-solubilized CUR.

Recent advances in Del Nido cardioplegia: A comprehensive analysis of randomized clinical trials in adult cardiac surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. METHODS: We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. RESULTS: In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: -6.01, 95% CI [-11.14, -0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: -537.17, 95% CI [-758.89, -315.45]), troponin T (MD: -1.71, 95% CI [-2.11, -1.32]), creatine phosphokinase-MB (MD: -2.96, 95% CI [-5.84, -0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. CONCLUSION: No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Comparison Between Histidine-Tryptophan-Ketoglutarate Cardioplegia and Cold Blood Cardioplegia for Myocardial Protection in Tetralogy of Fallot Patients Undergoing Surgical Repair: A Randomized Clinical Trial.

OBJECTIVES: This study was conducted to compare the efficacy of histidine-tryptophan-ketoglutarate (HTK) cardioplegia and cold blood cardioplegia (CBC), especially for postoperative right ventricular (RV) function after tetralogy of Fallot repair. DESIGN: Randomized, double-blinded, parallel-group, controlled clinical trial. SETTING: Ain Shams University Hospitals. PARTICIPANTS: A total of 100 children (1 to 5 years old) scheduled for tetralogy of Fallot repair. INTERVENTIONS: Patients were allocated (double-blinded 1:1 allocation ratio) to either the HTK group that received HTK cardioplegia (30 mL/kg via antegrade route) or the CBC group that received cold blood cardioplegia with blood-to-Ringer solution (4:1) in a volume of 20 mL/kg. MEASUREMENTS AND MAIN RESULTS: The HTK group showed a statistically significant reduction of the vasoactive inotropic score on admission to the pediatric intensive care unit (13.0 ± 4.1) in comparison to the CBC group (15.5 ± 5.4), with a p value of 0.011. However, after 24 hours, the vasoactive-inotropic score was comparable. Lactate level during the first 24 hours was 6.2 ± 0.7 mmol/L in the HTK group and 6.9 ± 0.4 mmol/L in the CBC group (p < 0.0001). Serial troponin measurements were lower in the HTK group (1.49 ± 0.45) compared to the CBC group (1.69 ± 0.18) at the first 72 hours postoperatively (p = 0.005). Postoperative echocardiographic assessment of RV function by means of tricuspid annular plane systolic excursion and myocardial performance index were better in the HTK group than in the CBC grpup (p < 0.05). CONCLUSIONS: HTK cardioplegia may offer better cardiac protection to pediatric patients undergoing tetralogy of Fallot repair than our institutional standard CBC with better recovery for the hypertrophic RV.

Prolongation of the Time Window From Traumatic Limb Amputation to Replantation From 6 to 33 Hours Using Ex Vivo Limb Perfusion.

INTRODUCTION: Continuous extracorporeal perfusion (ECP), or machine perfusion, holds promise for prolonged skeletal muscle preservation in limb ischemia-reperfusion injury. This study aimed to extend the amputation-to-replantation time window from currently 6 hours to 33 hours using a 24-hour ECP approach. MATERIALS AND METHODS: Six large white pigs underwent surgical forelimb amputation under general anesthesia. After amputation, limbs were kept for 9 hours at room temperature and then perfused by 24-hour ECP with a modified histidine-tryptophan-ketoglutarate (HTK) solution. After ECP, limbs were orthotopically replanted and perfused in vivo for 12 hours. Clinical data, blood, and tissue samples were collected and analyzed. RESULTS: All 6 forelimbs could be successfully replanted and in vivo reperfused for 12 hours after 9 hours of room temperature ischemia followed by 24 hours ECP. Adequate limb perfusion was observed after replantation as shown by thermography and laser Doppler imaging. All pigs survived without severe organ failure, and no significant increase in inflammatory cytokines was found. Macroscopy and histology showed marked interstitial muscular edema of the limbs, whereas myofiber necrosis was not evident, implying the preservation of muscular integrity. CONCLUSIONS: The use of a 24-hour ECP has successfully extended limb preservation to 33 hours. The modified histidine-tryptophan-ketoglutarate perfusate demonstrated its ability for muscle protection. This innovative approach not only facilitates limb replantation after combat injuries, surmounting geographical barriers, but also broadens the prospects for well-matched limb allotransplants across countries and continents.

Postoperative Hydration in Children Using Intermittent Boluses of Balanced Salt Solution: Results of a Randomized Control Trial.

BACKGROUND: Postoperative maintenance fluids are traditionally provided via hypotonic dextrose containing fluids administered intravenously by continuous infusion. We hypothesized that scheduled weight-based boluses of balanced salt solution would be more physiologic, reduce fluid volumes, and improve patient comfort. METHODS: As part of an IRB-approved randomized controlled trial (Boluses of Ringer's in Surgical Kids, BRiSK), we randomized patients aged 1-21 years undergoing elective abdominal or thoracic surgery to post-operatively receive weight-based D50.45NS+20mEq/L KCl at a continuous rate or intermittent boluses of Lactated Ringer's solution until oral liquid toleration. Patients with nephropathy, diabetes, or receiving parenteral nutrition were excluded. We analyzed electrolytes, urine output, fluid volume, and adverse events. RESULTS: We enrolled and randomized 60 patients: 29 to continuous fluids and 31 to bolus fluids. One patient from the bolus group dropped out. No patients crossed over due to difficulties with application of the bolus protocol. There were no baseline differences between groups with a mean age of 12.6 ± 1.4yr and weight of 50.9 ± 7.2 kg. There were no serious adverse events or electrolyte disturbances in either group. Patients in the bolus group received significantly less total fluid than those in the continuous group (0.43 mL/kg/h vs 1.1 mL/kg/h, p < 0.001) with no difference in urine output [1.4 ± 0.2 mL/kg/h vs 1.6 ± 0.3 mL/kg/h, p = 0.211]. There were two episodes of mild hypoglycemia in the bolus group compared to seven episodes of mild hyperglycemia in the continuous group. CONCLUSIONS: Administration of post-operative intravenous fluids as boluses of balanced salt solution is feasible, safe, and results in significantly less fluid administered compared to a traditional continuous protocol. LEVEL OF EVIDENCE: II.

Low Calcium-High Magnesium Krebs-Henseleit Solution Combined with Adenosine and Lidocaine Improved Rat Aortic Function and Structure Following Cold Preservation.

Background and objectives: The main problem of vascular preservation is the maintenance of vessel graft quality and function following extended storage. Conventional preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution, Phosphate-Buffer Solution (PBS), or sodium chloride 0.9% has been shown to be inadequate in preserving vascular physiological function after 3 days of cold storage. This study aimed to evaluate whether adenosine and lidocaine (AL) in a modified Krebs-Henseleit (KH) solution can preserve the function and histological structure of rat aortic rings after 6 days. Materials and Methods: Thirty-five aortic rings from male Wistar rats (200-300 g) were harvested and immediately immersed in one of the assigned cold preservation solutions: standard KH, modified KH (mod KH) with lower calcium (Ca2+) and higher magnesium content (Mg2+) with or without adenosine and lidocaine (mod KH-AL), and modified KH with AL, insulin, and melatonin (Mod KH-ALMI). The contraction and relaxation function of the aortic rings were examined using an isometric force transducer after 6 days of cold preservation. Hematoxylin and eosin staining were used to analyze the rings' histological structure. Results: Vascular contraction and relaxation functions were severely affected after a 6-day cold storage period in standard KH. Modifying the KH solution by reducing the Ca2+ and increasing the Mg2+ levels greatly recovered the vessel functions. The addition of AL or ALMI to the modified KH did not further recover vascular contractility. However, only the addition of AL to the modified KH increased the ACh-induced relaxation at 6 days when compared to the conventional KH, suggesting that endothelium preservation is improved. From histological analysis, it was found that the addition of AL but not ALMI further improved the endothelial lining and the structure of the elastic membrane layers of the preserved vessels after 6 days of cold preservation. Conclusions: The addition of AL to low calcium-high magnesium KH solution significantly enhanced endothelial preservation and improved endothelial-induced relaxation of preserved vessels after 6 days of cold storage.

Molecular basis of human noradrenaline transporter reuptake and inhibition.

Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.

Evaluation of the texture characteristics and taste of shrimp surimi with partial replacement of NaCl by non­sodium metal salts.

Ionic strength plays a significant role in the aggregation behavior of myofibrillar proteins. The study investigated the effects of KCl or CaCl2 as substitutes for NaCl on the gel properties and taste of shrimp surimi at a constant ionic strength (IS = 0.51). Increased KCl substitution ratio resulted in a reduction in α-helix content and an increase in ß-sheet content of myofibrillar proteins, thereby enhancing water holding capacity. Optimal KCl substitutions (1.5% NaCl +1.94% KCl) contributed to maintaining the desired taste and improving gel properties. CaCl2 facilitates the extraction and dissolution of myofibrillar proteins, resulting in an organized and dense gel network with significant water-holding capacity. However, excessive additions (>1.27%) resulted in a notable decrease in taste and gel strength due to excessive aggregation and precipitation of myofibrillar proteins. These findings provide a solid theoretical foundation for production of high-quality, low-salt shrimp surimi.

Comparative analysis of del Nido cardioplegia versus blood cardioplegia in isolate coronary artery bypass grafting.

BACKGROUND: This study examined the efficacy of del Nido cardioplegia compared with traditional blood cardioplegia in adult cardiac surgery for isolated coronary artery bypass grafting by evaluating the early postoperative outcomes. METHODS: A total of 119 patients who underwent isolated conventional coronary artery bypass grafting were enrolled and divided into two groups (del Nido cardioplegia group [n = 36] and blood cardioplegia group [n = 50]) based on the type of cardioplegia used. This study compared the preoperative characteristics, intraoperative data, and early postoperative outcomes. Further subgroup analyses were conducted for high-risk patient groups. RESULTS: The 30-day mortality and morbidity rates were not significantly different between groups. The del Nido cardioplegia group exhibited advantageous myocardial protection outcomes, demonstrated by a significantly smaller rise in Troponin I levels post-surgery (2.8 [-0.4; 4.2] vs. 4.5 [2.9; 7.4] ng/mL, p = 0.004) and fewer defibrillation attempts during weaning off of cardiopulmonary bypass (0.0 ± 0.2 vs. 0.4 ± 1.1 times, p = 0.011) when compared to the blood cardioplegia group. Additionally, the del Nido group achieved a reduction in surgery duration, as evidenced by the reduced aortic cross-clamping time (64.0 [55.5; 75.5] vs. 77.5 [65.0; 91.0] min, p = 0.001) and total operative time (287.5 [270.0; 305.0] vs. 315.0 [285.0; 365.0] min, p = 0.008). Subgroup analyses consistently demonstrated that the del Nido cardioplegia group had a significantly smaller postoperative increase in Troponin I levels across all subgroups (p < 0.05). CONCLUSIONS: del Nido cardioplegia provided myocardial protection and favorable early postoperative outcomes compared to blood cardioplegia, making it a viable option for conventional coronary artery bypass grafting. Establishing a consensus on the protocol for Del Nido cardioplegia administration in adult surgeries is needed.

Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

Direct Visualization of a Cesarean Scar Ectopic Pregnancy After Medical Management.

BACKGROUND Cesarean scar ectopic pregnancy is a rare type of ectopic pregnancy that can result in severe maternal morbidity and mortality. Medical, surgical, and minimally invasive therapies alone or in combination have been described in the literature, but the optimal treatment modality of cesarean scar ectopic pregnancies is unknown. Limited information exists on the course of cesarean scar ectopic pregnancy following treatment with cytotoxic agents. CASE REPORT We present a case of a woman with a history of multiple cesarean births that was provided with medical abortion for an unintended pregnancy. However, upon follow-up, the patient was found to have a cesarean scar ectopic pregnancy. Following the diagnosis, she was treated by multi-dose systemic methotrexate-leucovorin and with ultrasound-guided intra-gestational sac injection of potassium chloride. After resolution of beta human gonadotropin levels, ultrasound follow-up revealed persistence of residual tissue in the cesarean scar. The patient elected for resection of the residual tissue with operative hysteroscopy. We report a novel hysteroscopic finding after medical treatment of a cesarean scar ectopic pregnancy with intra-gestational sac injection of potassium chloride. CONCLUSIONS Direct visualization of the intra-abdominal cavity and intra-uterine cavity showed that combined medical management with systemic methotrexate and local potassium chloride injection is an effective treatment modality for live cesarean scar ectopic pregnancies, with minimal anatomical harm. Hysteroscopic resection offers a safe and effective approach for removal of persistence of residual tissue.

Salting-out and Competitive Adsorption of Ethanol into Lipid Bilayer Membranes: Conflicting Effects of Salts on Ethanol-Membrane Interactions Studied by Molecular Dynamics Simulations.

Small amphiphilic molecules, such as ethanol, disturb the structure of lipid bilayer membranes to increase the membrane permeability, which is important for applications such as drug delivery, disinfection, and fermentation. To investigate how and the extent to which coexisting salts affect membrane disturbance, we performed molecular dynamics (MD) simulations on lipid bilayer membranes composed of zwitterionic lipids in aqueous ethanol solutions containing 0-631 mM NaCl, KCl, and KI salts. The addition of salts at low concentrations induced cationic adsorption on the lipid membrane, which competes with ethanol adsorption, thereby reducing the hydrogen bonds between ethanol and lipid molecules. This competitive adsorption mitigated the membrane disturbance and decreased the permeation of ethanol molecules into the membrane. In contrast, higher salt concentrations enhanced the membrane disturbance and permeability, which was caused by the salting-out of ethanol from the aqueous phase to the lipid bilayer. These conflicting effects appearing at different concentrations were stronger with the chloride salts than with the iodide salt. Among the two chloride salts, NaCl and KCl, the latter showed a greater enhancement in ethanol permeation at high concentrations. This seeming anti-Hofmeister salting-out behavior resulted from greater Na+ adsorption, preventing the ethanol-lipid interactions.

Flanking Effect on the Structure and Stability of Human Telomeric G-Quadruplex in Varying Salt Concentrations.

The stability of the human telomere G-quadruplex (G4) is directly linked to cancer disease. The human telomere is mostly associated with the flanking nucleobases, which can affect the stability of G4. Hence, in this study, the effect of the flanking nucleobases in the context of their chemical nature, number, and position on the structure and stability of G4 has been investigated in varying concentrations of KCl mimicking the normal and cancer KCl microenvironments. The addition of flanking nucleobases does not alter the G4 topology. However, the presence of merely a single flanking nucleobase destabilizes the telomeric G4. This destabilizing effect is more prominent for thymine than adenine flanking nucleobase, probably due to the formation of the intermolecular G4 topology by thymine. Interestingly, the change in the stability of the telomeric G4 in the presence of thymine flanking nucleobase is sensitive to the concentration of KCl relevant to the normal and cancerous microenvironments, in contrast to adenine. Flanking nucleobases have a greater impact at the 5' end compared to the 3' end, particularly noticeable in KCl concentrations resembling the normal microenvironment rather than the cancerous one. These findings indicate that the effect of the flanking nucleobases on telomeric G4 is different in the KCl salt relevant to normal and cancerous microenvironments. This study may be helpful in attaining molecular-level insight into the role of G4 in telomeric length regulation under normal and cancerous KCl salt conditions.

Quality changes due to refrigerated storage in a traditional dry-cured pork belly salted with glasswort or KCl as partial substitutes for NaCl.

BACKGROUND: Glasswort represents a novel alternative to KCl for replacing sodium in meat products. To evaluate the effects of Na reduction on the quality changes of a traditional dry cured belly due to storage, fresh bellies were dry-salted with 2% NaCl (BCON), with 2% of a mixture containing 50% NaCl and 50% KCl (BKCl) or with 1% of a mixture of 90% NaCl and 10% powdered glasswort (BGW), dry-cured, sliced, vacuum packaged and stored under refrigeration for 60 days. RESULTS: The BKCl and BGW bellies were lower in sodium by one-third to one-half compared to BCON (with 1.6 g Na/100 g). Neither BKCl, nor BGW significantly differed from BCON in free fatty acids (FFA) before and after storage, whereas BGW showed almost twice as much 2-methylbutanal content as BCON. All bellies showed microbiological stability during storage. Micrococcaceae was the most abundant microbial group with values of 105 to 106 colony-forming units g-1. The BGW presented higher Micrococcaceae counts (approximately one log unit) but lower microbial biodiversity than BCON. CONCLUSION: The two alternative dry salting methods reduced the sodium content in bellies, at the same time as ensuring chemical and microbiological stability during refrigerated vacuum storage. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.