Search Results (48)

Intravenous medications are frequently administered through shared catheter lines in neonatal intensive care units (NICUs) due to the limited venous access in preterm infants, raising concerns about drug incompatibilities that may cause serious complications. Hydrocortisone sodium (HDC), ampicillin (ABPC), and cefotaxime (CTX) are commonly used in NICUs and are often co-administered with unfractionated heparin (UFH), which is routinely infused to prevent catheter occlusion. This study evaluated the physicochemical compatibility of HDC, ABPC, and CTX when mixed with UFH. Each drug was combined with UFH at equal volumes, and the mixtures were assessed immediately and after 3 h of storage by visual inspection, pH measurement, UV absorbance, and HPLC-UV analysis. No precipitation, turbidity, or color changes were observed in any mixture, and UV absorbance showed no relevant deviations compared with controls. Slight pH variations were detected but remained within acceptable limits. In semi-quantitative HPLC analysis, relative peak area changes were all below 10%, indicating no major degradation of the drugs. These findings suggest that HDC, ABPC, and CTX maintain acceptable physicochemical compatibility when co-administered with UFH, supporting their safe concomitant use in NICU practice. Full article

Background/Objectives: We developed and validated a robust and simple LC–MS/MS method for the simultaneous quantification of amoxicillin and clavulanate in human plasma relative to previously reported methods. Methods: Amoxicillin; clavulanate; and an internal standard, 4-hydroxytolbutamide, in human K₂-EDTA plasma, were deproteinized with acetonitrile and then subjected to back-extraction using distilled water–dichloromethane. Separation was performed on a Poroshell 120 EC-C₁₈ column with a mobile-phase gradient comprising 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.5 mL/min within 6.5 min. The negative electrospray ionization modes were utilized to monitor the transitions of m/z 363.9→223.1 (amoxicillin), m/z 198.0→135.8 (clavulanate), and m/z 285.0→185.8 (4-hydroxytolbutamide). Results/Conclusions: Calibration curves exhibited linear ranges of 10–15,000 ng/mL for amoxicillin (r ≥ 0.9945) and 20–10,000 ng/mL for clavulanate (r ≥ 0.9959). Intra- and inter-day’s coefficients of variation, indicating the precision of the assay, were ≤7.08% for amoxicillin and ≤10.7% for clavulanate, and relative errors in accuracy ranged from −1.26% to 10.9% for amoxicillin and from −4.41% to 8.73% for clavulanate. All other validation results met regulatory criteria. Partial validation in lithium–heparin, sodium–heparin, and K₃-EDTA plasma confirmed applicability in multicenter or large-scale studies. This assay demonstrated itself to be environmentally friendly, as assessed by the Analytical GREEnness (AGREE) tool, and was successfully applied to a clinical pharmacokinetic study of an Augmentin^® IR tablet (250/125 mg). The inter-individual variabilities in clavulanate exposures (AUC_t and C_max) were significantly greater than in amoxicillin, and they may inform the clinical design of future drug–drug interaction. Full article

Propolis is a natural resinous substance produced by honeybees that has many biological activities. For thousands of years, it has been widely used as a dietary supplement and traditional medicine to treat a variety of ailments due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties. Nutritional supplements and foods may interact with drugs both pharmacodynamically and pharmacokinetically, which could raise clinical concerns. Background/Objectives: This study aimed to investigate the effect of propolis on the plasma disposition of enrofloxacin and to assess the potential pharmacokinetic interaction in rabbits. Methods: In this study, enrofloxacin was applied per os (20 mg/kg) and IM (10 mg/kg) and with propolis (100 mg resin/kg) administration in four groups of rabbits (each of six individuals). Heparinized blood samples were collected at 0, 0.1, 0.3, 0.5, 1, 2, 4, 8, 12, and 24 h post-administration. HPLC-FL was used to analyze the plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following liquid–liquid phase extraction, i.e., protein precipitation with acetonitrile and partitioning with sodium sulfate. Results: The results revealed that propolis coadministration significantly affected the plasma disposition of enrofloxacin and its active metabolite after both per os and intramuscular administration routes. Significantly greater AUC (48.91 ± 11.53 vs. 26.11 ± 12.44 µg.h/mL), as well as longer T_1/2λz (11.75 ± 3.20 vs. 5.93 ± 2.51 h) and MRT (17.26 ± 4.55 vs. 8.96 ± 3.82 h) values of enrofloxacin and its metabolite ciprofloxacin, were observed after the coadministration of propolis compared to enrofloxacin alone following both per os and IM routes in rabbits. Conclusions: The concurrent use of propolis and prescription medications may prolong the half-life (T_1/2λz) and increase the systemic availability of chronically used drugs with narrow therapeutic indices. The repeated use of drugs such as antibiotics, heart medications, and antidepressants, or drugs with a narrow therapeutic index such as antineoplastic and anticoagulant agents, can cause toxic effects by raising blood plasma levels. Considering the varied metabolism of rabbits and humans, further validation of this study may require thorough clinical trials in humans. Full article

Background/Objectives: Bladder pain syndrome (BPS), or painful bladder syndrome (PBS)/interstitial cystitis (IC), is a chronic inflammatory condition characterized by symptoms like pain, urgency, urinary incontinence, and sometimes urinary retention, which significantly affect patients’ quality of life. The etiology of PBS/IC remains unclear and may be multifactorial, with no definitive treatment currently available. The challenge lies in finding new therapeutic strategies. Various intravesical treatments, such as heparin, hyaluronic acid, and botulinum toxin, are commonly used for PBS/IC. In this study, we aimed to evaluate the anti-inflammatory effects of intravesical Vessilen^® (a new formulation consisting of 2% adelmidrol and 0.1% sodium hyaluronate) in patients with IC/PBS or other bladder disorders. Methods: This was a pilot study conducted at a tertiary-level urogynecology center. Two validated questionnaires were administered to patients before and after treatment: the Visual Analogue Scale (VAS) and the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS Long Form). The Patient Global Impression (PGI) scale was used to assess symptom severity. Results: Among the 25 patients who completed six weekly instillations, a significant decrease in bladder symptoms was observed, as indicated by both the ICIQ-FLUTS scale (89.3 vs. 61.3; p = 0.021) and VAS score (4.4 vs. 2.6; p < 0.001). Additionally, 80% of patients reported symptom improvement (PGI-I score ≤ 3). Conclusions: Intravesical Vessilen^® (adelmidrol + sodium hyaluronate) appears to be an innovative therapeutic approach for PBS/IC and other chronic inflammatory bladder disorders due to its anti-inflammatory and antinociceptive properties. Full article

hiPSC-derived blood–brain barrier (BBB) models are valuable for pharmacological and physiological studies, yet their translational potential is limited due to insufficient cell phenotypes and the neglection of the complex environment of the BBB. This study evaluates the plasma compatibility with hiPSC-derived microvascular endothelial-like cells to enhance the translational potential of in vitro BBB models. Therefore, plasma samples (sodium/lithium heparin, citrate, EDTA) and serum from healthy donors were tested on hiPSC-derived microvascular endothelial-like cells at concentrations of 100%, 75%, and 50%. After 24 h, cell viability parameters were assessed. The impact of heparin-anticoagulated plasmas was further evaluated regarding barrier function and endothelial phenotype of differentiated endothelial-like cells. Finally, sodium-heparin plasma was tested in an isogenic triple-culture BBB model with continuous TEER measurements for 72 h. Only the application of heparin-anticoagulated plasmas did not significantly alter viability parameters compared to medium. Furthermore, heparin plasmas improved barrier function without increasing cell density and induced a von Willebrand factor signal. Finally, continuous TEER measurements of the triple-culture model confirmed the positive impact of sodium-heparin plasma on barrier function. Consequently, heparin-anticoagulated plasmas were proven to be compatible with hiPSC-derived microvascular endothelial-like cells. Thereby, the translational potential of BBB models can be substantially improved in the future. Full article

This study aims to explore the impact of adding sodium acetate and sodium butyrate on the composition, blood biochemical parameters, and volatile flavor compounds of lactating mares’ milk. By assessing the influence of these additives on milk flavor enhancement, the findings provide scientific evidence for optimizing flavor characteristics and offer new strategies for improving the sensory attributes of mare milk products. Eighteen lactating Yili mares were randomly assigned to three groups: a control group, a sodium acetate group (85 mg/kg·BM⁻¹), and a sodium butyrate group (85 mg/kg·BM⁻¹). The experiment lasted 90 days, with milk yield recorded on days 0, 30, 60, and 90. Milk samples were collected on day 60 (peak lactation) for compositional analysis, and GC-IMS was employed to identify and quantify volatile compounds. Additionally, blood samples were drawn from the jugular vein before morning feeding on day 60 using heparinized tubes to assess key biochemical markers, including glucose, triglycerides, total cholesterol, and urea. The results revealed the following findings: (1) Milk yield and composition: The addition of sodium acetate and sodium butyrate had no significant effect on milk yield. However, both treatment groups exhibited significantly or extremely significantly higher milk fat content compared to the control group, whereas milk protein and lactose levels remained largely unchanged. (2) Blood biochemical indicators: The sodium butyrate group showed an extremely significant increase in urea levels compared to the sodium acetate and control groups. Glucose levels in the sodium acetate group were also significantly higher than in the control group. Moreover, triglyceride levels were markedly elevated in the sodium butyrate group compared to the sodium acetate group, while total bilirubin concentrations were significantly higher in the sodium acetate group than in the control group. (3) Volatile compounds: The addition of these additives led to a significant increase in the diversity and concentration of volatile compounds in mare milk. Notably, esters, aldehydes, and ketones showed substantial enrichment in both treatment groups. The relative abundance of esters such as butyl acetate, L-lactic acid ethyl ester, 1-pentene-3-ol, pentanol, and 3-pentanone increased, alongside a significant rise in aldehydes and ketones, including 2-heptenal and 3-pentanone. In conclusion, sodium acetate and sodium butyrate enhance milk flavor by modulating milk composition and metabolic parameters, providing a scientific foundation for improving the quality of mare milk products. Full article

Current research demonstrates the expanding therapeutic potential of heparin derivatives in oncology, extending beyond traditional anticoagulation mechanisms. This systematic analysis examines the structural characteristics, molecular mechanisms, and therapeutic applications of heparin-based compounds in malignancy treatment. The essential antithrombin binding pentasaccharide sequence has enabled development of specialized molecular variants, particularly fractionated heparins and their non-anticoagulant counterparts. These agents exert antineoplastic effects via multiple pathways, particularly through modulation of heparanase enzymatic activity and specific protein–glycosaminoglycan interactions. Evidence from pivotal clinical trials (FRAGMATIC, MAGNOLIA, GASTRANOX) confirms efficacy in managing cancer-associated thrombosis while indicating potential enhancement of chemotherapeutic outcomes. The preparation methods utilize enzymatic cleavage reactions and selective chemical derivatization to generate structurally modified heparins exhibiting unique molecular characteristics and biological activities. Analysis of the glycosaminoglycan analog dociparstat sodium reveals significant activity in myeloid malignancies, mediated by specific interference with CXCL12/CXCR4 signaling cascades. Significant challenges remain in manufacturing scale-up, analytical validation, and long-term safety assessment. Future studies must address dose optimization, combination strategies, and controlled clinical trials to determine the full therapeutic potential of these compounds in clinical oncology. Full article

Background/Objectives: The skin is an important barrier that protects against invasion by foreign substances and retains water in the body. Several skin diseases involve dry skin due to a disrupted skin barrier, and most skin diseases that appear on dry skin are accompanied by itch. Dry skin-induced itch and mechanical alloknesis reduce quality of life. Sulfated hemicellulose (i.e., pentosan polysulfate sodium), similar to heparin, is a compound belonging to the sulfated polysaccharide family; however, in contrast to heparin, it is derived from plant materials. We herein investigate the effects of the topical application of OJI-204, a sulfated hemicellulose made by purifying and chemically synthesizing hemicellulose, on dry skin in a mouse model. Methods: The mouse model of dry skin was generated using a mixture of acetone and ether with water. Either OJI-204 (3% or 10%) or 0.3% heparinoid, PBS (control), was applied twice a day to the acetone and diethyl ether/water (AEW)-treated area. The degree of skin dryness was evaluated by measuring transepidermal water loss and stratum corneum hydration. Scratching behavior was recorded the day before AEW treatment and the day after the final day, and an alloknesis assay was performed on the day after the final day. Results: We found that 3% or 10% OJI-204 attenuated dry skin conditions (erythema/hemorrhage, scarring/dryness, edema, and excoriation/erosion) and itchiness more effectively than 0.3% heparinoid. Furthermore, the degree of dryness improved to the same degree as that with heparinoid. OJI-204 also significantly reduced dry skin-induced spontaneous itch and mechanical alloknesis. Conclusions: These results suggest the potential of OJI-204 as a therapeutic or preventive agent for dry skin. Full article

(1) Background: Danaparoid sodium is a heparinoid antithrombotic that has been used for over 40 years for prophylaxis of DVT in non-HIT patients and for the treatment of heparin-induced thrombocytopenia (HIT) with and without thrombosis. This update summarises current information on its pharmacology and reviews danaparoid dose management in a broad spectrum of clinical situations, including off-label indications. (2) Methods: Evidence from published clinical studies, case reports, compassionate use of danaparoid, and spontaneously reported serious adverse events is summarised and analysed by an interdisciplinary expert group to develop a consensus on dosing regimens of danaparoid for complex clinical situations, including vulnerable patient populations. (3) Results: Dosing regimens are proposed, together with monitoring recommendations and target anti-factor Xa ranges. (4) Conclusion: In a comprehensive summary detailed interdisciplinary dosing recommendations are described to provide a basis for safe and effective use of danaparoid. Full article

Introduction: This systematic review aims to analyze the current literature regarding 30-day mortality and postoperative acute kidney disease (AKI) in complex abdominal aortic aneurysms (cAAAs), which included juxtarenal aortic aneurysm (JAA), suprarenal aortic aneurysm (SRAA), and type IV thoracoabdominal aortic aneurysm (TAAA) open surgery (OS), to evaluate the impact of renal perfusion on AKI and to try to define which is the best way to perform it. Methods: A literature search in PubMed and Cochrane Library was performed, and articles published from January 1986 to January 2024 reporting on JAA, SRAA, and TAAA type IV open surgery management were identified. Multicenter studies, single-center series, and case series with ≥10 patients were considered eligible. Comparisons of outcomes of patients who underwent OS for complex abdominal aortic aneurysms (cAAAs) with or without perfusion of the renal arteries were analyzed when available. The titles, abstracts, and full texts were evaluated by two authors independently. The primary outcomes included AKI and 30-day mortality rates. The new-onset dialysis rate was considered a secondary outcome. Results: A total of 295 articles were evaluated, and 21 were included, totaling 5708 patients treated for cAAAs with OS. The male patients totaled 4094 (71.7%), with a mean age of 70.35 ± 8.01 and a mean renal ischemia time of 32.14 ± 12.89 min. Data were collected and analyzed, at first in the entire cohort and then divided into two groups (no perfusion of the renal arteries—group A vs. selective perfusion—group B), with 2516 patients (44.08%) who underwent cAAAs OS without perfusion of the renal arteries and 3192 patients (55.92%) with perfusion. In group B, four types of renal perfusion were reported. Among the 21 studies included, 10 reported on selective renal perfusion in cAAA OS, with several types of fluids described: (1) “enriched” Ringer’s solution, (2) “Custodiol” (Istidine-tryptophan-ketoglutarate or Custodiol HTKsolution), (3) other cold (4 °C) solutions (i.e., several combinations of 4 °C isotonic heparinized balanced salt solution containing mannitol, sodium bicarbonate, and methylprednisolone), and (4) warm blood. Thirty-day mortality for patients in group A was 4.25% (107/2516) vs. 4.29% (137/3192) in group B. The reported incidence of AKI and new onset of dialysis was, respectively, 22.14% (557/2516) and 5.45% (137/2516) for group A and 22.49% (718/3192) and 4.32% (138/3192) for group B. A total of 579 patients presented with chronic kidney disease (CKD) at admission across all studies, which included 350 (13.91%) in group A vs. 229 (7.17%) in group B. Acute kidney injury, 30-day mortality, and new-onset dialysis rate were reported in four subgroups: (1) In the “Ringer” group, 30-day mortality was 2.52% (3/113), AKI affected 27.73% (33/119) of patients, and the new-onset dialysis rate was 2.52% (3/113). (2) In the “Custodiol” group, 30-day mortality was 3.70% (3/81), AKI affected 20.17% (24/81) of patients, and the new-onset dialysis rate was 2.46% (2/81). (3) In the “cold solutions” group (i.e., NaCl and mannitol), 30-day mortality was 4.38% (130/2966), AKI affected 21.81% (647/2966) of patients, and the new-onset dialysis rate was 4.48% (133/2966). (4) In the “Warm blood” group, 30-day mortality was 3.85% (1/26), AKI affected 53.84% (14/26) of patients, and the new-onset dialysis rate was 0% (0/26). Conclusions: This systematic review highlights the lack of standard definitions for AKI, CKD, and the type of renal perfusion. Despite similar results in terms of AKI and 30-day mortality, renal perfusion seems to be protective of the new-onset hemodialysis rate. Moreover, Custodiol appears to have lower rates of AKI and hemodialysis than the other perfusion types. A prospective randomized controlled trial to perform further subgroup analysis and research the various types of renal perfusion may be necessary to identify possible benefits. Full article

The integration of unmanned aerial vehicles or uncrewed aerial vehicles (UAVs)—commonly known as drones—into medical logistics offers transformative potential for the transportation of sensitive medical materials, such as blood samples. Traditional car transportation is often hindered by traffic delays, road conditions, and geographic barriers, which can compromise timely delivery. This study provides a comprehensive analysis comparing high-speed drone transportation with traditional car transportation. Blood samples, including EDTA whole blood, serum, lithium-heparin plasma, and citrate plasma tubes, were transported via both methods across temperatures ranging from 4 to 20 degrees Celsius. The integrity of the samples was assessed using a wide array of analytes and statistical analyses, including Passing–Bablok regression and Bland–Altman plots. The results demonstrated that drone transportation maintains blood sample integrity comparable to traditional car transportation. For serum samples, the correlation coefficients (r) ranged from 0.830 to 1.000, and the slopes varied from 0.913 to 1.111, with minor discrepancies in five analytes (total bilirubin, calcium, ferritin, potassium, and sodium). Similar patterns were observed for EDTA, lithium-heparin, and citrate samples, indicating no significant differences between transportation methods. Conclusions: These findings highlight the potential of drones to enhance the efficiency and reliability of medical sample transport, particularly in scenarios requiring rapid and reliable delivery. Drones could significantly improve logistical operations in healthcare by overcoming traditional transportation challenges. Full article

Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways. Full article

Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be used in therapy. In this research, a well-known CP, polypyrrole (PPy), was synthesized in the presence of the polysaccharide heparin (HEP) and chlorpromazine (CPZ) using sodium dodecyl sulfate (SDS) as electrolyte on a steel substrate. The obtained results demonstrate the successful incorporation of CPZ and HEP into the polymer matrix, with the deposited films maintaining stable electrochemical parameters across multiple doping/dedoping cycles. Surface roughness, estimated via AFM analysis, revealed a correlation with layer thickness—decreasing for thinner layers and increasing for thicker ones. Moreover, SEM images revealed a change in the morphology of PPy films when PPy is electropolymerized in the presence of CPZ and HEP, while FTIR confirmed the presence of CPZ and HEP within PPy. Due to its lower molecular mass compared to HEP, CPZ was readily integrated into the thin polymer matrix during deposition, with diffusion being unimpeded, as opposed to films with greater thickness. Finally, the resulting system exhibited the ability to release CPZ, enabling a dosing range of 10 mg to 20 mg per day, effectively covering the therapeutic concentration range. Full article

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at ‘high-end’ clinical concentrations and physically incompatible with 16 drugs and six ‘2-in-1’ parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters. Full article

Cell-free RNAs (cfRNAs) are promising analytes as non-invasive biomarkers and have even greater potential if tied in with metabolomics. Plasma is an optimal source for cfRNAs but is often derived from a variety of anticoagulants. Plasma obtained in heparin is suitable for metabolomics but is difficult to utilize for qPCR-based downstream analysis. In the present study, we aimed to develop a simple, time-efficient, and cost-effective heparinase protocol, followed by library preparation and sequencing of human plasma cfRNAs drawn and stored in heparin at −80 °C for several years. Blood was collected in CPT™ sodium heparin tubes from patients with chronic HCV infection (NCT02400216) at the National Institutes of Health (NIH) Clinical Center. Plasma cfRNAs were treated with heparinase I and used for library preparation and next-generation sequencing (NGS). Heparinase treatment maintained RNA integrity and allowed for successful library preparation for all the study subjects even with 7 ng of cfRNAs as starting material. The classification report derived from Pavian R package v1.2.0 showed no artificial reads. The abundance of chordate over microbial reads suggests no addition of experimental error through heparinase I treatment. We report a novel and practical approach to heparinase treatment for human plasma collected and frozen in sodium heparin for several years. This is an effective demonstration of utilizing heparin plasma for NGS and downstream transcriptomic research, which could then be integrated with metabolomics from the same samples, maximizing efficiency and minimizing blood draws. Full article