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Scientific Reports Jul 2023Biocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes...
Biocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes used in dialysis. Oxone-mediated TEMPO-oxidized cellulose nanomaterials have been demonstrated to be excellent additives in the production and tunability of ultrafiltration and dialysis membranes. In the present study, nanocellulose ionic liquid membranes (NC-ILMs) were tested in vitro and ex vivo. An increase in flux of up to two orders of magnitude was observed with increased rejection (about 99.6%) of key proteins compared to that of polysulfone (PSf) and other commercial membranes. NC-ILMs have a sharper molecular weight cut-off than other phase inversion polymeric membranes, allowing for high throughput of urea and a uremic toxin surrogate and limited passage of proteins in dialysis applications. Superior anti-fouling properties were also observed for the NC-ILMs, including a > 5-h operation time with no systemic anticoagulation in blood samples. Finally, NC-ILMs were found to be biocompatible in rat ultrafiltration and dialysis experiments, indicating their potential clinical utility in dialysis and other blood filtration applications. These superior properties may allow for a new class of membranes for use in a wide variety of industrial applications, including the treatment of patients suffering from renal disease.
Topics: Rats; Animals; Renal Dialysis; Ultrafiltration; Toxins, Biological; Dialysis Solutions; Proteins; Membranes, Artificial; Urea
PubMed: 37474512
DOI: 10.1038/s41598-023-37765-y -
PloS One 2023Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in... (Clinical Trial)
Clinical Trial
Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options. Trial registration: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis.
Topics: Young Adult; Humans; Feasibility Studies; Microdialysis; Clinical Protocols; Dialysis Solutions; Glioma
PubMed: 37682953
DOI: 10.1371/journal.pone.0291068 -
Frontiers in Medicine 2024Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. However, there are challenges in terms of dedicated... (Review)
Review
Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. However, there are challenges in terms of dedicated pharmaceutical solutions and targeted interventions for POP. The primary characteristics of POP include compromised mechanical properties of uterine ligaments and dysfunction within the vaginal support structure, often resulting from delivery-related injuries. Fibroblasts secrete extracellular matrix, which, along with the cytoskeleton, forms the structural foundation that ensures proper biomechanical function of the fascial system. This system is crucial for maintaining the anatomical position of each pelvic floor organ. By systematically exploring the roles and mechanisms of biomechanical-biochemical transformations in POP, we can understand the impact of forces on the injury and repair of these organs. A comprehensive analysis of the literature revealed that the extracellular matrix produced by fibroblasts, as well as their cytoskeleton, undergoes alterations in patient tissues and cellular models of POP. Additionally, various signaling pathways, including TGF-β1/Smad, Gpx1, PI3K/AKT, p38/MAPK, and Nr4a1, are implicated in the biomechanical-biochemical interplay of fibroblasts. This systematic review of the biomechanical-biochemical interplay in fibroblasts in POP not only enhances our understanding of its underlying causes but also establishes a theoretical foundation for future clinical interventions.
PubMed: 38410754
DOI: 10.3389/fmed.2024.1303044 -
BMJ Open Nov 2023Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for...
INTRODUCTION
Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis.
METHODS AND ANALYSIS
This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation.
ETHICS AND DISSEMINATION
The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Registry (NCT06069336).
Topics: Child; Humans; Infant; Saline Solution; Nebulizers and Vaporizers; Bronchiolitis; Saline Solution, Hypertonic; Administration, Inhalation; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38011984
DOI: 10.1136/bmjopen-2023-080182 -
PloS One 2023Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common...
Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common clinical signs result from damage to red blood cells and hepatocytes, and this intoxication is considered a model for the induction of acute liver failure. In the present study, the hepatoprotective effects of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC) against experimental paracetamol (PAR) poisoning were analysed. Thirty-five adult Wistar rats (Rattus novergicus albinus) were randomly assigned to five groups, and thirty-one of these survived the treatments. Negative control group (CON-) received 1mL of 0.9% NaCl orally (PO). Other groups received 1.2g/kg of PAR (PO). Positive control group (CON+) received only PAR. NAC group received 800 mg/kg intraperitoneally (IP) of NAC 1h after the administration of PAR and at 12 h received 1mL of 0.9% NaCl, IP. The fourth group (CoQ10) received 1h and 12 h after intoxication, CoQ10 (10mg/kg IP). And the fifth group (NAC+CoQ10) received NAC (800mg/kg, IP) and CoQ10 (10mg/kg, IP). After 12 hours, the rats were euthanized and necropsied to collect liver and kidney tissues for histopathological evaluation and electronic microscopy. A single dose of PAR caused severe acute hepatitis. NAC couldn't reverse the liver and kidney damages. The group that received CoQ10 and NAC had moderate liver damage, while the group that received only CoQ10 had lower values of liver enzymes and mild liver and kidney damage. Animals that received treatment with CoQ10 or NAC+CoQ10 presented normal hepatocyte mitochondria and nuclei. Although CoQ10 couldn't reverse PAR organ damage, results indicate promising hepatoprotection in Wistar rats.
Topics: Adult; Humans; Rats; Animals; Acetylcysteine; Acetaminophen; Rats, Wistar; Saline Solution
PubMed: 37607187
DOI: 10.1371/journal.pone.0290268 -
Scientific Reports Jul 2023This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical... (Randomized Controlled Trial)
Randomized Controlled Trial
This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps < 0.05). Compared with the SLT group, the latanoprost group had a significant and stable decrease in IOP after treatment. The latanoprost group had a more pronounced reduction in IOP at weeks 4 and 12 (P < 0.05) but had no difference at week 1 (P = 0.097). As a first-line treatment, both SLT and latanoprost eye drops are effective in newly diagnosed POAG and OHT patients. However, the latanoprost eye drops may be better in decreasing mean and peak 24-h IOP and thus controlling 24-h IOP fluctuation compared to SLT.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Trabeculectomy; Ophthalmic Solutions; Prospective Studies; Antihypertensive Agents; Ocular Hypertension; Glaucoma; Intraocular Pressure; Laser Therapy; Lasers; Treatment Outcome
PubMed: 37500642
DOI: 10.1038/s41598-023-38550-7 -
MAbs 2024Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different...
Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) solutions, we measured the viscosities, the second virial coefficients, the Kirkwood-Buff integrals, and the cluster distributions of the antibody molecules as functions of protein concentration. Solutions were modeled using the statistical-physics Wertheim liquid-solution theory, representing antibodies as Y-shaped molecular structures of seven beads each. We found that high-viscosity solutions result from more antibody molecules per cluster. Multi-body properties such as viscosity are well predicted experimentally by the 2-body Kirkwood-Buff quantity, , but not by the second virial coefficient, , and well-predicted theoretically from the Wertheim protein-protein sticking energy. Weakly interacting antibodies are rate-limited by nucleation; strongly interacting ones by propagation. This approach gives a way to relate micro to macro properties of solutions of associating proteins.
Topics: Antibodies, Monoclonal; Humans; Solutions; Viscosity
PubMed: 38666507
DOI: 10.1080/19420862.2024.2339582 -
BMC Anesthesiology Dec 2023Bicarbonate Ringer's (BR) solution is a direct liver and kidney metabolism-independent HCO buffering system. We hypothesized that BR solution would be more effective in... (Randomized Controlled Trial)
Randomized Controlled Trial
Bicarbonate ringer's solution could improve the intraoperative acid-base equilibrium and reduce hepatocellular enzyme levels after deceased donor liver transplantation: a randomized controlled study.
BACKGROUND
Bicarbonate Ringer's (BR) solution is a direct liver and kidney metabolism-independent HCO buffering system. We hypothesized that BR solution would be more effective in improving acid-base equilibrium and more conducive to better liver function than Acetate Ringer's (AR) solution in conventional orthotopic liver transplantation (OLT) patients.
METHODS
Sixty-nine adult patients underwent OLT. Patients in the bicarbonate and acetate groups received BR solution or AR solution as infused crystalloids and graft washing solution, respectively. The primary outcome was the effect on pH and base excess (BE) levels. The secondary outcome measures were the incidence and volume of intraoperative 5% sodium bicarbonate infusion and laboratory indicates of liver and kidney function.
RESULTS
The pH and absolute BE values changed significantly during the anhepatic phase and immediately after transplanted liver reperfusion in the bicarbonate group compared with the acetate group (all P < 0.05). The incidence and volume of 5% sodium bicarbonate infusion were lower in the bicarbonate group than in the acetate group (all P < 0.05). The aspartate transaminase (AST) level at 7 postoperative days and the creatine level at 30 postoperative days were significantly higher in the acetate group than in the bicarbonate group (all P < 0.05).
CONCLUSION
Compared with AR solution, BR solution was associated with improved intraoperative acid-base balance and potentially protected early postoperative liver graft function and reduced late-postoperative renal injury.
Topics: Adult; Humans; Liver Transplantation; Acid-Base Equilibrium; Ringer's Solution; Bicarbonates; Sodium Bicarbonate; Carcinoma, Hepatocellular; Liver Neoplasms; Living Donors; Isotonic Solutions; Acetates
PubMed: 38114893
DOI: 10.1186/s12871-023-02383-8 -
Peritoneal Dialysis International :... Jan 2024Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is... (Review)
Review
Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is the most important functional change, and peritoneal fibrosis is the major morphological alteration. Both are caused by the continuous exposure to dialysis solutions that are different from plasma water with regard to the buffer substance and the extremely high-glucose concentrations. Glucose has been incriminated as the major cause of long-term peritoneal membrane changes, but the precise mechanism has not been identified. We argue that glucose causes the membrane alterations by peritoneal pseudohypoxia and by the formation of advanced glycosylation end products (AGEs). After a summary of UF kinetics including the role of glucose transporters (GLUT), and a discussion on morphologic alterations, relationships between function and morphology and a survey of the pathogenesis of UF failure (UFF), it will be argued that impaired UF is partly caused by a reduction in small pore fluid transport as a consequence of AGE-related vasculopathy and - more importantly - in diminished free water transport due to pseudohypoxia, caused by increased peritoneal cellular expression of GLUT-1. The metabolism of intracellular glucose will be reviewed. This occurs in the glycolysis and in the polyol/sorbitol pathway, the latter is activated in case of a large supply. In both pathways the ratio between the reduced and oxidised form of nicotinamide dinucleotide (NADH/NAD ratio) will increase, especially because normal compensatory mechanisms may be impaired, and activate expression of hypoxia-inducible factor-1 (HIF-1). The latter gene activates various profibrotic factors and GLUT-1. Besides replacement of glucose as an osmotic agent, medical treatment/prevention is currently limited to tamoxifen and possibly Renin/angiotensis/aldosteron (RAA) inhibitors.
Topics: Humans; Peritoneal Dialysis; Glucose; Glycosylation; Peritoneum; Dialysis Solutions; Water; Ultrafiltration
PubMed: 37723976
DOI: 10.1177/08968608231196033 -
Contact Lens & Anterior Eye : the... Aug 2023Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and...
BACKGROUND AND OBJECTIVES
Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and hyaluronic acid (HA) in women aged 42-54 years (mixed-hormonal status) versus ≥ 55 years (postmenopausal) and with moderate and severe DED.
METHODS
This was a post-hoc analysis of three clinical trials assessing the efficacy of artificial tears containing trehalose (3%) and HA (0.15%) in women with an Ocular Surface Disease Index (OSDI) ≥ 18. Patients instilled one drop of the artificial tears in each eye 3 to 6 times daily and were evaluated at baseline and after 84 ± 7 days for DED symptom severity (OSDI), hyperemia (McMonnies scale), tear break-up time (TBUT), corneal and conjunctival staining (Oxford and Van Bjisterveld scales), tear production (Schirmer I test), and ocular symptoms.
RESULTS
A total of 273 women were evaluated, 61 of age 42-54 years; 212 of ≥ 55 years. DED symptoms, as measured by the OSDI, decreased significantly with the treatment in both age groups (p < 0.0001). Conjunctival hyperemia decreased significantly and TBUT increased significantly in both groups, especially in women of age 42-54 (both p < 0.0001). The global (corneal and conjunctival) staining score decreased significantly in both groups, but also more in women of age 42-54 years. No differences were observed between age groups for any of the variables measured, except for visual acuity. DED symptoms were consistently reported more frequently by the mixed hormonal status women, but also the effect of the treatment was more pronounced in this group.
CONCLUSIONS
Artificial tears with trehalose and HA significantly improved the symptoms of DED in women aged 42-54 and ≥ 55 years. The decrease in symptoms was more pronounced in women of age 42-54 years, suggesting better mechanisms of recovery from inflammation and loss of ocular surface homeostasis.
Topics: Humans; Female; Male; Lubricant Eye Drops; Hyaluronic Acid; Trehalose; Hyperemia; Dry Eye Syndromes; Tears
PubMed: 37117131
DOI: 10.1016/j.clae.2023.101845