Ringer's Solution Research Articles

Volume of intraoperative normal saline versus lactated Ringer's solution on acute kidney injury: A secondary analysis of the SOLAR trial.

Evaluate whether intraoperative crystalloid volume modifies the relationship between the AKI risk and treatment group. Secondary analysis of a single-center multiple cross-over cluster trial. Intraoperative care. We enrolled 8616 adults who had colorectal or orthopedic surgery at a large academic institution. Clusters of patients were alternately assigned to intraoperative normal saline or lactated Ringer's solution. The primary outcome was the incidence of acute kidney injury (AKI) as a function of intraoperative crystalloid volume (0-1, 1-2, 3-4, or 4+ liters) and the type of crystalloid. Our secondary outcome was the change in postoperative serum chloride concentration during the first 24h. The risk of AKI did not differ significantly in patients given 0-1, 1-2, or 3-4L saline or lactated Ringers solutions. In contrast, patients given 2-3 or>4L of lactated Ringer's solution had a higher risk of AKI than those given saline. Patients assigned to normal saline had progressively greater plasma chloride concentrations than those given lactated Ringer's across all volume categories. While saline administration clearly causes volume-dependent hyperchloremia, we found no evidence to support the theory that large volumes of saline provoke AKI. Therefore, either fluid seems reasonable for intraoperative use.

Nanoscale visualization of the anti-tumor effect of a plasma-activated Ringer's lactate solution.

Plasma-activated Ringer's lactate solutions (PALs), which are Ringer's lactate solutions treated with non-thermal atmospheric-pressure plasma, have an anti-tumor effect and can be used for chemotherapy. As the anti-tumor effect of the PAL is influenced by the cell-treatment time, it is necessary to monitor the structural changes of the cell surface with non-invasive, nanoscale, and time-lapse imaging to understand the anti-tumor effect. In this study, to characterize the anti-tumor effect of the PAL, we used scanning ion conductance microscopy (SICM), using glass nanopipettes as probes, to visualize the structural changes of the cell surface. SICM time-lapse topographic imaging visualized a decrease in the movement of lamellipodia in normal cells and cancer cells after the PAL treatment. Furthermore, in normal cells, protrusive structures were observed on the cell surface. Time-lapse imaging using SICM allowed us to characterize the differences in the morphological changes between the normal and cancer cells upon exposure to the PAL.

High-volume lactated Ringer's solution with human albumin versus standard-volume infusion as a prophylactic treatment for post-endoscopic retrograde cholangiopancreatography pancreatitis: randomized clinical trial.

Adverse events after endoscopic retrograde cholangiopancreatography (ERCP) are rare, and post-ERCP pancreatitis is a serious adverse event. This study aimed to determine the role of aggressive intravenous hydration with lactated Ringer's solution at a specific volume with 20% human albumin before ERCP in reducing the incidence of post-ERCP pancreatitis. This study was a single-centre randomized clinical trial. The participants were randomly assigned to two groups: those who received aggressive intravenous hydration with 20% human albumin and lactated Ringer's solution (intervention group), and those who received standard-volume intravenous hydration with lactated Ringer's solution (control group). The primary endpoint was post-ERCP pancreatitis. Participants and outcome assessors were blinded to treatment allocation. Comparison was performed using the chi-square, the Fisher's exact, the Student's t, or the Mann-Whitney U tests, where appropriate. Of 300 randomized participants, 149 and 144 participants from the intervention and control group were included in the analysis. There was no significant difference in the post-ERCP pancreatitis rate (n = 10; 6.7% versus n = 9; 6.3%, P = 0.873) between the intervention and control groups. High-risk procedures (that is pancreatic duct wiring, pancreatic duct injection, precut sphincterotomy, and balloon dilation of the ampulla) were significantly associated with post-ERCP pancreatitis compared with low-risk procedures (n = 15; 15% versus n = 4; 2.1%, P < 0.001). In the high-risk procedures population, the intervention and control groups had increased post-ERCP pancreatitis rates (P = 0.716). Two participants in each group developed pulmonary congestion. Aggressive peri-ERCP intravenous hydration with lactated Ringer's solution combined with 50 ml of 20% human albumin did not prevent post-ERCP pancreatitis. None of the subgroups presented with prophylactic effects. Thai Clinical Trials Registry (TCTR20240405003).

Design and Characterization of Novel Polymeric Hydrogels with Protein Carriers for Biomedical Use.

Hydrogels are three-dimensional polymeric matrices capable of absorbing significant amounts of water or biological fluids, making them promising candidates for biomedical applications such as drug delivery and wound healing. In this study, novel hydrogels were synthesized using a photopolymerization method and modified with cisplatin-loaded protein carriers, as well as natural extracts of nettle (Urtica dioica) and chamomile (Matricaria chamomilla L.). The basic components of the hydrogel were polyvinylpyrrolidone and polyvinyl alcohol, while polyethylene glycol diacrylate was used as a crosslinking agent and 2-methyl-2-hydroxypropiophenone as a photoinitiator. The hydrogels demonstrated high swelling capacities, with values up to 4.5 g/g in distilled water, and lower absorption in Ringer's solution and simulated body fluid (SBF), influenced by ionic interactions. Wettability measurements indicated water contact angles between 51° and 59°, suggesting balanced hydrophilic properties conducive to biomedical applications. Surface roughness analyses revealed that roughness values decreased after incubation, with Ra values ranging from 6.73 µm before incubation to 5.94 µm after incubation for samples with the highest protein content. Incubation studies confirmed the stability of the hydrogel matrix, with no significant structural degradation observed over 20 days. However, hydrogels containing 2.0 mL of protein suspension exhibited structural damage and were excluded from further testing. The synthesized hydrogels show potential for application as carriers in localized drug delivery systems, offering a platform for future development in areas such as targeted therapy for skin cancer or other localized treatments.

Observational study for multiparametric assessment of cardiac congestion in outpatient worsening heart failure (EVOLUTION).

We sought to characterize the clinical course of patients following worsening heart failure (WHF) treated in an outpatient setting and to identify factors associated with a poor response to standard of care with loop diuretics. Between September 2022 and March 2023, 44 eligible patients (mean age 66.3 years, 84% male) with ejection fraction <50% and with WHF symptoms in the preceding week treated in an outpatient setting were enrolled. Patients were assessed weekly over 4 weeks following the WHF episode. At week 4, responses to fluid expansion and furosemide administration were assessed in 39 patients to unmask persistent subclinical congestion. Patients were on stable doses of guideline-directed medical therapy (GDMT) with a mean daily furosemide dose of 47.4 mg. Patient-reported and physician-assessed symptoms and quality of life improved over the 4 weeks. At 1 h following 1 L Ringer solution infused over 2 h, the median (interquartile range) urine volume and urine sodium excreted over 3 h were 300 (200.0-500.0) ml and 39.6 (12.4-63.0) mEq, respectively. Receiver-operating characteristic curves suggest that cystatin C >1.2 ng/ml, N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1500 pg/ml, and high-sensitivity troponin T >20 pg/ml represent good predictors of non-response to a fluid challenge (diuresis, natriuresis, and rales) following an outpatient WHF, with having all three markers associated with the worst response. Patients with high levels of troponin, or NT-proBNP, or cystatin C who develop WHF despite being treated with a loop diuretic, need novel therapies for WHF.

Bioactive Properties of Phosphate-Modified Silicon Oxycarbide Protective Coatings: Morphology and Functional Evaluation.

This article presents a study on the functional properties and morphology of coatings based on amorphous silicon oxycarbide modified with phosphate ions and comodified with aluminum and boron. The objective of this modification was to enhance the biocompatibility and bioactivity without affecting its protective properties. The comodification was aimed toward stabilization of phosphate in the structure. The coatings were prepared according to the typical procedure for polymer-derived ceramics: synthesized via the sol-gel method, deposited using the dip-coating technique, and subsequently pyrolyzed. Comprehensive analyses of the morphology, surface properties, corrosion resistance, and bioactivity were conducted to assess their functional performance. The coatings exhibited uniform and smooth surfaces, with phase separation observed in the boron-modified SiBPOC series. Surface wettability and free energy measurements demonstrated that SiPOC and SiBPOC coatings possessed moderate hydrophilicity and favorable surface free energy for cell adhesion and bone tissue mineralization. Corrosion resistance tests in Ringer's solution revealed that SiBPOC coatings provided the highest protection against ion leaching, while SiAlPOC showed decreased resistance due to surface cracks. Bioactivity tests indicated calcium phosphate precipitation on the surface of all samples with higher hydroxyapatite formation on SiPOC and SiAlPOC coatings. In vitro tests using MG-63 osteoblast-like cells confirmed the biocompatibility of the coatings, with SiPOC and SiBPOC exhibiting the best combination of bioactivity, cell adhesion, and proliferation. These findings suggest that the phosphate- and boron-modified SiOC-based coatings are promising candidates for enhancing bone integration in orthopedic implants.

Assessment of change in end-tidal CO2 after fluid challenge as a marker of fluid responsiveness as measured by the aortic velocity time integral in healthy anesthetized mechanically ventilated dogs.

To evaluate if variation in the end-tidal CO2 partial pressure (∆Petco2) after a fluid challenge could predict fluid responsiveness with a sensitivity of 75% and a specificity of 70% in healthy anesthetized and mechanically ventilated dogs. Diagnostic accuracy study. University hospital. Twenty-seven dogs admitted for neutering. To obtain a balanced sample between fluid responder and nonresponder dogs, a 10-mL/kg lactated Ringer's solution was administered over 15minutes to half of the population before the baseline measurements. All animals then received a fluid challenge of 10mL/kg lactated Ringer's solution in 5minutes. The velocity-time integral of aortic blood flow (VTIAo) was evaluated with Doppler echocardiography before and after a fluid challenge to classify the included dogs as fluid responders or nonresponders. Fluid responsiveness was defined as an increase of ≥15% of the VTIAo after the fluid challenge. Petco2 was evaluated at 1, 5, and 10(T1,T5,T10)minutes after fluid expansion. Area under the receiver operating characteristic curve (AUROC) analysis was used to assess the ability of ∆Petco2 to predict fluid responsiveness at different time points. A total of 13 dogs were fluid responders, and 14 were nonresponders. The best predictive capacity for ∆Petco2 was observed at T10. The AUROC with its 95% confidence interval (CI) for ∆Petco2 at T10 was 0.75 (0.56-0.93), with a sensitivity of 84.62% (95% CI, 54.60-98.10), a specificity of 64.29% (95% CI, 35.10-87.20), a positive predictive value of 68.80% (95% CI, 41.30-89.00), and a negative predictive value of 81.80% (95% CI, 48.20-97.70). The optimal cutoff was 1mmHg. The current study showed that, although minimal, ∆Petco2 predicted fluid responsiveness in the dogs studied.

Behavior of PGS/apatite foam scaffolds during incubation in SBF, PBS, Ringer's solution, artificial saliva, and distilled water.

Poly(glycerol sebacate) is a polymeric material with potential biomedical application in the field of tissue engineering. In order to act as a biodegradable scaffold, its incubation study is vital to simulate its behavior. This study explores the degradation of porous poly(glycerol sebacate)/hydroxyapatite scaffolds subjected to incubation in various physiological solutions. The research involved monitoring pH and conductivity values over a 14-day period, as well as analyzing the swelling capacity and mass alterations of the scaffolds. In simulated body fluid (SBF) and phosphate-buffered saline (PBS), the pH levels remained relatively stable, whereas Ringer's solution caused a pH decrease. Conversely, artificial saliva demonstrated an increase in pH, and distilled water caused a slight decrease. The conductivity values remained stable in SBF and Ringer's solution, slightly decreased in PBS, increased in artificial saliva, and significantly increased in distilled water. The swelling capacity of the scaffolds varied depending on the solution used, with the lowest equilibrium swelling observed in SBF and PBS. The effect of the presence of ceramics on this parameter was also observed. The mass changes of the scaffolds indicated deposition of particles or salts from the incubation solutions, and subsequent rinsing in distilled water led to a decrease in mass. Scanning electron microscopy (SEM) imaging and elemental analysis confirmed the presence of crystallized salts on the scaffold surfaces after incubation in SBF. Surface roughness measurements revealed changes in roughness depending on the solution, with deposition of additional layers in SBF and degradation in artificial saliva. In summary, the scaffolds exhibited biodegradation in physiological solutions, with variations in pH, conductivity, swelling capacity, mass changes, and surface morphology depending on the specific solution and scaffold composition.

Intraoperative Use of Sodium Bicarbonate Ringer's Solution Instead of Sodium Lactate Ringer's Solution to Reduce Endothelial Glycocalyx Degradation and Improve Postoperative Recovery During Cardiopulmonary Bypass Cardiac Surgery: A Single-Center Prospective Cohort Study.

To investigate the effect of sodium bicarbonate Ringer's solution (BRS) on the degradation of endothelial glycocalyx components in patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, and to evaluate its impact on endothelial glycocalyx preservation and postoperative recovery. A total of eight patients scheduled for elective CPB heart surgery were included and randomly divided into two groups: the sodium lactate Ringer's solution (LRS) group and the BRS group. ELISA was used to measure plasma concentrations of syndecan-1, matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3), IL-6, IL-8, TNF-α, and TGF-β at predefined time points: T0 (before induction of anesthesia), T3 (immediately after weaning from CPB), T5 and T6 (24 and 72hours postoperatively). Serum creatinine concentrations were measured within 48hours postoperatively. The incidence of postoperative delirium (POD) was assessed three days after surgery. Postoperative mechanical ventilation time, duration of stay in the intensive care unit and hospital stay were also documented. The BRS group had significantly lower plasma concentrations of syndecan-1 at T3 (7.98 [7.43, 8.92] ng/mL vs 9.54 [8.4, 10.73] ng/mL, P < 0.001) and T5 (4.20 [3.31, 4.96] ng/mL vs 5.40 [3.95, 6.55] ng/mL, P = 0.001) in comparison with the LRS group (P<0.01). Syndecan-1 levels in both groups were similar at T6 (3.18 [2.88, 3.5]ng/mL vs 3.12 [2.77, 3.45] ng/mL, P > 0.05). Additionally, MMP-9, MMP-3, IL-6 and IL-8 were significantly lower at T3 and T5 in the BRS group (P<0.05 and P<0.01, respectively). However, no significant differences were observed between the two groups in the incidence of acute kidney injury (AKI) or POD (P > 0.05). BRS has the potential to reduce glycocalyx degradation in patients undergoing heart valve surgery with CPB. However, both groups demonstrated similar post-postoperative clinical outcomes, including the rates of AKI and POD.

Sidestream dark field video microscopy demonstrates shelf-stable blood products preserve the endothelial glycocalyx in a canine hemorrhagic shock model.

To utilize sidestream dark field video microscopic technology to evaluate the endothelium in a canine hemorrhagic shock and resuscitation model. 6 purpose-bred adult dogs were anesthetized, instrumented, and subjected to hemorrhagic shock from September 2021 through June 2022. Each dog was resuscitated with 5 resuscitation strategies in an experimental crossover design study: (1) lactated Ringer's solution (LRS) and hydroxyethyl starch (HES) solution; (2) canine chilled whole blood (CWB); (3) canine fresh frozen plasma (FFP) and packed RBCs (pRBC); (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC); or (5) HBOC/FDP and canine lyophilized platelets. Sidestream dark field video microscopic evaluation was performed at 5 time points: commencement, after hemorrhage, after shock, after resuscitation (T135), and conclusion (T180). There was a significant difference between the perfused boundary region (PBR) measurements when comparing the LRS/HES resuscitation arm to the CWB and FFP/pRBC resuscitation arms at T180. A significant difference in PBR was appreciated in the LRS/HES arm at T135 and T180 compared to its baseline. No other significant differences in PBR were appreciated when resuscitation arms were compared longitudinally or to each other. Shelf-stable blood products preserved the endothelial glycocalyx similarly to CWB and pRBC/FFP as evaluated by sidestream dark field video microscopy. Lactated Ringer and HES solutions did not adequately preserve the endothelial glycocalyx compared to CWB and pRBC/FFP. Shelf-stable blood products are a viable option to preserve the endothelial glycocalyx when used during hemorrhagic resuscitation in dogs.

Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults.

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVCmax in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.NEW & NOTEWORTHY We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.

Cholera outbreak in Mayotte (France): A retrospective description of 16 patients treated for hypovolemia in the ICU.

To describe the presentation and therapeutic management of severe cholera in Mayotte (France). We carried out retrospective data collection. All patients treated in the intensive care unit (ICU) with a confirmed diagnosis of cholera by PCR were studied. Only patients treated for hypovolemia were included. Out of the 215 confirmed cases of cholera in Mayotte on July 12, 2024, 25 required treatment in the ICU (11.6 %). Among these cases, 16 were treated for hypovolemia (7.4 %), while five patients died of cholera before they could be admitted to hospital (lethality rate 2.32 %). No patient died in hospital. Median patient age was 17 years (4-30) with a sex ratio of 1. Severe diarrhea was the rule with a median of one diarrheal stool every two hours. Clinical severity was characterized by sunken eyes and Glasgow Coma Scale (GCS) < 14 (n = 16/16,100 %). Biological severity was determined by profound metabolic acidosis with venous pH < 7.20 (n = 16/16, 100 %). Intravenous fluid therapy was aggressive with a median of 280 mL/kg (230-300) Ringer's lactate solution during the first 48 h. Cholera can be a life-threatening infection, with deaths occurring due to severe diarrhea and hypovolemia. From the onset of symptoms, which are sometimes fulminant, patients must be admitted to a care center as soon as possible. We will continue to collect data to create scores that will enable us to better recognize the most severe forms of the disease.

In Vitro and In Vivo Translational Insights into the Intraoperative Use of Antiseptics and Lavage Solutions Against Microorganisms Causing Orthopedic Infections.

The growing antibiotic resistance of microorganisms causing postoperative infections following orthopedic surgeries underscores the urgent need for localized antiseptic and lavage delivery systems to enhance infection control. This study evaluates the in vitro effectiveness of antiseptic and lavage solutions-including polyhexanide, povidone-iodine, low-concentrated hypochlorite, Ringer's solution, and saline-against Staphylococcus epidermidis, Staphylococcus aureus MRSA, Cutibacterium acnes, Corynebacterium amycolatum, Pseudomonas aeruginosa, and Candida albicans. Using microplate models (Minimum Inhibitory Concentration, Minimum Biofilm Eradication Concentration, and Biofilm-Oriented Antiseptic Test assays), flow-based models (Bioflux system), and surfaces relevant to orthopedic implants (e.g., stainless steel disks/screws, Co-Cr-Mo, Ti-Al-Nb orthopedic alloys, and ultra-high-molecular-weight polyethylene), as well as a bio-nano-cellulose scaffold representing tissue, we assessed the solutions' activity. The cytotoxicity of the solutions was evaluated using osteoblast and keratinocyte cell lines, with additional in vivo insights gained through the Galleria mellonella larval model. The results show that polyhexanide-based solutions outperformed povidone-iodine in biofilm eradication in most tests applied, particularly on complex surfaces, whereas iodine demonstrated higher cytotoxicity in applied in vitro and in vivo tests. Low-concentration hypochlorite solutions exhibited minimal antibiofilm activity but also showed no cytotoxicity in cell line and G. mellonella larval models. These findings highlight the importance of careful antiseptic selection and rinsing protocols to balance infection control efficacy with tissue compatibility in orthopedic applications.

Arthroscopically assisted suture osteosynthesis of tibial eminence fractures in children and adolescents

The surgical goal is the arthroscopically assisted, closed reduction, and suture osteosynthesis of fractures of the tibial eminence in children and adolescents. Fractures of the tibial eminence type (II)-III according to Meyers & McKeever or typeIV according to Zaricznyj. Fracture of the tibial eminence typeI, conservatively treatable fracture typeII according to Meyers & McKeever and ligamentous rupture of the anterior cruciate ligament. Supine position. Securing the leg with alateral support on the thigh and aroll to support the foot in90° kneeflexion. Unwrap for blood evacuation with cuff on the thigh. Creation of the anterolateral portal and filling of the joint with Ringer's solution. Usually, extensive irrigation of the hemarthrosis is required first to gain visibility. Then the anteromedial portal is created. Adiagnostic walk-around is performed to rule out concomitant injuries to the cartilage and menisci. The fracture bed is then debrided with the shaver and the fracture is reduced on atrial basis using the cruciate ligament targeting device. Remove the cruciate ligament targeting device and reinforce the anterior cruciate ligament (ACL) with asuture shuttle forceps with two 1PolysorbTM sutures (Medtronic, Minneapolis, MN, USA), which are discharged and secured via the anteromedial portal. Now reinsert the cruciate ligament targeting device via the anteromedial portal. This is set to an angle of a good 60°. The image converter is used for control. Skin incision in the area of the 3 mm drill sleeve. Now a 2.4 mm cannulated drill with a core is used to predrill into the joint medial to the tibial eminence, strictly epiphyseal depending on the age. After removing the core of the drill, a wire loop is inserted into the joint, grasped with the forceps and also passed out via the anteromedial portal. Now remove the drill while leaving the wire loop in place. The medial thread legs are now threaded through the lasso loop and passed out distally via the drill channel. The analogous procedure is performed via the anterolateral portal so that the legs of both sutures meet ventrally at the tibial epiphysis/metaphysis. Now complete extension of the knee, reduction of the fracture with the cruciate ligament targeting device, under image converter control hand-tight knotting and, thus, firm reduction of the fracture. Suction of the joint. Layered wound closure. Application of a femoral cast sleeve in full extension. Removal of the osteosynthesis material is unnecessary with this method. Immobilization is in the femoral cast sleeve for 6 weeks. Removal of the femoral cast sleeve and radiological consolidation control 6 weeks postoperatively. Then start physiotherapy to restore the anatomical range of motion and strengthen thigh muscles. We operated on 10 patients between 2019 and 2022. Of these, 60% were boys. Age ranged from 5-14 years with a median of 8 years and a mean of 8.6 years. The right and left knee were affected half each; 20% of the patients presented a type II injury and 80% a type III according to Meyers & McKeever. One patient had to be revised in the course due to a cyclops lesion. One patient also presented a partial ACL rupture intraoperatively, but this has not shown any clinical relevance in the postoperative course to date. In the Lysholm score, we achieved a mean of 90.4 points and a median of 97.5 points. The International Knee Documentation Committee (IKDC) score resulted in a mean of 90.9% and a median of 90.25%. In addition, the pre- and postoperative tibial slope and the postoperative range-of-motion values were collected.

A Comprehensive Review of Analytical Techniques for Quantifying Cyclin‐dependent Kinase 4 and 6 Inhibitors in Biological Samples, Bulk, and Pharmaceutical Samples

ABSTRACTCyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitors are utilized as a remedy for advanced hormone receptor‐positive, HER2‐negative breast cancer (BC). By targeting CDK4/6, these drugs inhibit the phosphorylation of the retinoblastoma protein during the early G1 phase, leading to cell cycle arrest, disruption of deoxyribonucleic acid replication, and effective suppression of cancer cell proliferation. Recently, there has been an increasing focus on the advancement of analytical techniques for the determination of CDK4/6 inhibitors. These analytical methods are essential in the enhancement and refinement of CDK4/6 inhibitors for the management of advanced BC. This review provides a comprehensive overview of the various analytical techniques used for the analysis of palbociclib, ribociclib, and abemaciclib, along with their metabolites in biological fluids (such as blood and urine samples), commercial products, Ringer's solution, and simultaneous estimation. High‐performance liquid chromatography and liquid chromatography‐mass spectrometry are the primary analytical techniques commonly employed for the analysis of CDK4/6 inhibitors. This analytical review also provides insights into pharmacokinetics and stability studies, as well as the use of analytical techniques in detecting impurities and determining the structure of degraded products.

Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.

Background/Objectives: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity. Using a mouse model of hemorrhagic shock that mimics the clinical condition of adult patients, we investigated whether treatment with a humanin analog, humanin-G, mitigates lung injury and whether its mechanisms of action are dependent on the catalytic AMPKα1 subunit activation. Methods: Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation. Results: Sex- and genotype-related differences were observed after hemorrhagic shock as lung neutrophil infiltration was more pronounced in the male AMPKα1 WT mice than the female WT mice; also, the male AMPKα1 KO mice experienced a significant decline in mean arterial blood pressure when compared to the male WT mice after resuscitation. The scores of histological lung injury were similarly elevated in all the male and female AMPKα1 WT and KO mice when compared to the control mice. At molecular analysis, acute lung injury was associated with the downregulation of AMPKα1/α2 catalytic subunits in the WT mice, whereas an increased activation of the signal transducer and activator of transcription-3 (STAT3) was observed in all the vehicle-treated groups. The in vivo administration of humanin-G ameliorated histological lung damage in all the groups of animals and ameliorated mean arterial blood pressure in the male AMPKα1 KO mice. The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice only but not in the KO mice. The beneficial results of humanin-G correlated with the lung cytosolic and nuclear activation of AMPKα in the male and female AMPKα1 WT groups, whereas STAT3 activation was not modified. Conclusions: In adult age, hemorrhage-induced acute lung injury manifests with sex-dependent characteristics. Humanin-G has therapeutic potential and the AMPKα1subunit is an important requisite for its inhibitory effects on lung leucosequestration, but not for the amelioration of lung alveolar structure or the hemodynamic effects of the peptide.

Evaluation of Platonia insignis Mart. (Bacuri Butter) and Biopolymers from the Puree of Allium cepa L. (Yellow Onion Bulb) for Wound Healing in Horses.

Background/Objectives: Skin injuries are common in the equine clinical practice, requiring effective treatment to support natural healing. Bacuri butter is gaining attention for its potential in wound healing and its anti-inflammatory, antimicrobial, and antioxidant properties. Natural polymers such as onion (Allium cepa) bioplastics have been investigated for their potential as occlusive dressings and for tissue regeneration. Methods: This study evaluated the healing process of experimentally induced skin wounds on horses treated with bacuri butter, washed onion film, and unwashed onion film. Clinical and histopathological analyses of the wounds were conducted in six clinically healthy horses over 28 days, with a control group receiving Ringer's lactate solution. The onion films were produced and characterized for their chemical structure and properties, while the bacuri butter was sourced and prepared for application. Results: All treatments, including the control group, promoted wound healing without relevant differences in wound contraction rates, gross aspect, or histopathological parameters. Conclusions: Therefore, despite minor variations observed in the clinical evaluations between the treatment groups, the bacuri butter or onion biopolymer showed no significant healing effect on skin wounds in horses. Additionally, this study showed the potential of equine models in testing novel therapeutic approaches for wound healing, benefiting both veterinary and human medicine.

Effect of crystalloid solution co-loading infusion rate on the dose requirements of prophylactic phenylephrine for preventing hypotension following combined spinal-epidural anesthesia for cesarean delivery

BackgroundIntravenous fluid administration and prophylactic vasopressor infusion are the primary methods for preventing spinal anesthesia-induced hypotension during cesarean delivery. However, evidence regarding the impact of different volumes of crystalloid solution on the phenylephrine infusion dosage for preventing this hypotension remains inconclusive. This study aimed to determine the effect of two IV fluid infusion rates (10 or 20 mL/kg/h) on phenylephrine requirement for preventing spinal anesthesia-induced hypotension.MethodsEighty healthy parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. Participants were randomly assigned to receive either 10 mL/kg/h (group 10) or 20 mL/kg/h (group 20) of lactated Ringer’s solution. The first patient in each group received 0.5 µg/kg/min of phenylephrine infusion immediately after intrathecal injection. The phenylephrine dose in subsequent patients was adjusted by increments or decrements of 0.05 µg/kg/min based on the previous patient’s response. The ED50 of phenylephrine infusion for preventing spinal-induced hypotension for cesarean delivery was estimated using a modified up-down sequential analysis, with probit analysis applied as a backup sensitivity analysis.ResultsThe ED50 values for preventing spinal anesthesia-induced hypotension were 0.30 µg/kg/min (95% CI, 0.29–0.32 µg/kg/min) for group 10, and 0.19 µg/kg/min (95% CI, 0.16–0.22 µg/kg/min) for group 20, respectively. The estimated relative potency for phenylephrine in group 10 compared to group 20 was 1.52 (95%CI, 1.24–1.97), showing a significant difference in the ED50 values between the two groups.ConclusionThis study found that a higher crystalloid co-loading rate significantly reduces prophylactic phenylephrine requirement for preventing spinal anesthesia induced hypotension.Trials registrationhttps://www.chictr.org.cn/showproj.html?proj=125918 (Trial number: ChiCTR2100048002).

ABCs of base therapy in neonatology: role of acetate, bicarbonate, citrate and lactate.

Metabolic acidosis is common in preterm and term newborn infants and may be attributed to a variety of etiologies, potentially requiring base therapy such as acetate or bicarbonate. However, concerns exist regarding potential harm of sodium bicarbonate due to intracellular acidosis, fluctuations in cerebral blood flow, and osmolar load with rapid infusions, with no improvement in survival when used during resuscitation. Alternative approaches to correct metabolic acidosis include the addition of acetate in parenteral nutrition, intravenous lactated Ringer's (LR) solution, and use of oral citrate. Current guidelines focus on addressing the underlying cause of acidosis, reserving the use of sodium bicarbonate (NaHCO3) for severe cases requiring acute correction, LR instead of saline for volume boluses and using acetate or citrate for slow correction to stabilize acid-base status. Further research is necessary to better understand the efficacy and safety of acetate, NaHCO3, and other base sources in treating metabolic acidosis in neonates.

Nanotube formation and coating of hydroxyapatite-polyvinyl alcohol-collagen composite on Ti-6Al-4V metal alloy

Abstract Ti-6Al-4V metal is widely used as an implantable material due to its biocompatibility and corrosion resistance; however, it has low bioactive properties. The formation of nanotubes and a hydroxyapatite-polyvinyl alcohol-collagen composite coating on Ti-6Al-4V metal aims to enhance its biocompatibility and bioactivity. The nanotube oxide layer Ti-6Al-4V was formed by the anodization method. The composite’s infrared spectrum showed characteristic absorption bands from Hydroxyapatite (HAp), polyvinyl alcohol, and collagen. The composite-coated Ti-6Al-4V metal, both non-nanotube, and nanotube, showed a typical diffraction pattern of HAp and titanium element. The electron microscope image showed the uniform granular form of HAp. The corrosion test results showed that composite-coated nanotube Ti-6Al-4V metal could not improve corrosion resistance. It is also relevant to the in vitro test in a lactate ringer solution that showed the higher Ca2+ ion of nanotube Ti-6Al-4V metal than that of non-nanotube Ti-6Al-4V metal.