Vitamin drinks improve palatability and reduce adverse events associated to polyethylene glycol electrolyte solutions.

Background: The unpleasant taste of polyethylene glycol (PEG) has been a hindrance to patients undergoing colonoscopy. Aim: This study aims to determine whether the addition of a vitamin drink (Mizone) to the 4L split-dose PEG regimen would be effective in improving the solution's palatability, and reducing patient discomfort during bowel preparation. Methods: The present prospective, single endoscopist-blinded, randomized controlled study randomly assigned patients into two groups: PEG + Mizone group (3.6 L of PEG solution plus 0.4 L of Mizone) and PEG group (4 L of PEG solution). Palatability was assessed using a Likert scale of 1-5. The adverse events, amount of unconsumed solution, and willingness to repeat the same process were recorded through a questionnaire. The present study was registered in the Chinese Clinical Trial Registry (ChiCTR2000034484). Results: A total of 132 patients were included. The demographic characteristics of these patients were comparable between the two groups. The palatability score (mean ± standard deviation [SD]) was higher in the PEG + Mizone group, when compared to the control group (4.00 ± 0.859 vs. 2.95 ± 0.999, p < 0.001). Furthermore, the incidence of nausea was lower in the PEG + Mizone group (9.1 % vs. 28.8 %, p = 0.004), while the other adverse events were similar between the two groups. The percentage of the completely consumed pre-prepared solution was significantly greater in the PEG + Mizone group (95.5 % vs. 78.8 %, p = 0.004). Furthermore, the willingness to repeat the same process was higher in the PEG + Mizone group (83.3 % vs. 42.4 %, p < 0.001). However, the consumption of either of these preparations did not significantly affect the electrolyte and blood glucose levels, and renal function. Conclusion: Compared to the conventional 4L PEG bowel preparation, the use of a vitamin drink (Mizone) as an adjuvant can improve the palatability, reduce adverse events, and increase the patient's willingness to undergo bowel preparation with the same regimen.

Polyethylene Glycol/Pullulan-Based Carrier for Silymarin Delivery and Its Potential in Biomedical Applications.

Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer's solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6-7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer's solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin-Ciocâlteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.

Phenolic Foam Preparation Using Hydrofluoroolefin Blowing Agents and the Toughening Effect of Polyethylene Glycol.

In this work, a new class of fourth-generation, zero ozone depletion potential, hydrofluoroolefin-based blowing agents were used to prepare phenolic foam. While hydrofluoroolefin blowing agents have been used previously to prepare polyurethane foams, few studies have been reported on their use in phenolic foams. We introduce an effective method for foam preparation using two low-boiling blowing agents, cis-1,1,1,4,4,4-hexafluoro-2-butene and trans-1,1,1,4,4,4-hexafluoro-2-butene, and their combinations with hexane. Traditionally, phenolic foams have been prepared using chlorofluorocarbons and hydrochlorofluorocarbons, which can have harmful effects on the environment due to their high ozone depletion potential or global warming potential. Conductor-like screening model for real solvents (COSMO-RS) modeling studies were performed to understand the effects of different blowing agent combinations on their boiling points. A series of phenolic foams were prepared by varying the concentration of the hydrofluoroolefin and the hydrofluoroolefin-hexane blowing agent combinations. The concentrations of the surfactant, Agnique CSO 30, and the toughening agent, polyethylene glycol, were also varied to yield a formulation with the optimal properties. The foams formulated with the hydrofluoroolefin-hexane mixture displayed a higher compressive strength and a lower thermal conductivity than those prepared with either hydrofluoroolefin or hexane alone. The cell microstructure of all the foams was examined using scanning electron microscopy. By introducing flexible chains into the resin matrix, PEG facilitates proper distribution of hydrofluoroolefin-hexane blowing agents and other reagents and thereby increases the mechanical strength of the foam.

Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box-Behnken design.

A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug's blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box-Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes.

Bio-Composite Films Based on Carboxymethyl Chitosan Incorporated with Calcium Oxide: Synthesis and Antimicrobial Activity.

The utilization of biopolymers incorporated with antimicrobial agents is extremely interesting in the development of environmentally friendly functional materials for food packaging and other applications. In this study, the effect of calcium oxide (CaO) on the morphological, mechanical, thermal, and hydrophilic properties as well as the antimicrobial activity of carboxymethyl chitosan (CMCH) bio-composite films was investigated. The CMCH was synthesized from shrimp chitosan through carboxymethylation, whereas the CaO was synthesized via a co-precipitation method with polyethylene glycol as a stabilizer. The CMCH-CaO bio-composite films were prepared by the addition of synthesized CaO into the synthesized CMCH using a facile solution casting method. As confirmed by XRD and SEM, the synthesized CaO has a cubic shape, with an average crystalline size of 25.84 nm. The synthesized CaO exhibited excellent antimicrobial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (>99.9% R). The addition of CaO into CMCH improved the mechanical and hydrophobic properties of the CMCH-CaO films. However, it resulted in a slight decrease in thermal stability. Notably, the CMCH-CaO10% films exhibited exceptional antimicrobial activity against E. coli (98.8% R) and S. aureus (91.8% R). As a result, such bio-composite films can be applied as an active packaging material for fruit, vegetable, or meat products.

Naphthalimide-Based Amphiphiles: Synthesis and DFT Studies of the Aggregation and Interaction of a Simplified Model System with Water Molecules.

Systems containing amphiphilic/pathic molecules have the tremendous capacity to self-assemble under appropriate conditions to form morphologies with well-defined structural order (systematic arrangement), nanometer-scale dimensions, and unique properties. In this work, the synthesis of novel naphthalimide-based amphiphilic probes that have 1,8-naphthalimide as the fluorescence signal reporting group, octyl as hydrophobic head, and PEG as hydrophilic tail, is described. These designed molecules represent a new class of self-assembling structures with some promising features. The lack of literature data on the use of 1,8-naphthalimides with cyclic and acyclic hydrophilic PEG fragments as self-assembling structures gives us the opportunity to initiate a new field in materials science. The successful synthesis of such structures is fundamental to synthetic chemistry, and computational studies of the aggregation and binding of water molecules shed light on the ability of these new systems to function as membrane water channels. This study not only expands the list of 1,8-naphthalimide derivatives but may also serve as a new platform for the development of membrane additives based on PEG-functionalized naphthalimides.

Effect of Anti-PEG Antibody on Immune Response of mRNA-Loaded Lipid Nanoparticles.

Lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines have been approved for use to combat coronavirus disease 2019 (COVID-19). The mRNA-LNPs contain PEG-conjugated lipids. Clinical studies have reported that mRNA-LNPs induce the production of anti-PEG antibodies, but the anti-PEG antibodies do not affect the production of neutralizing antibodies. However, the detailed influence of anti-PEG antibodies on mRNA-LNP vaccines remains unclear. Therefore, in this study, we prepared ovalbumin (OVA) as a model antigen-encoding mRNA-loaded LNP (mRNA-OVA-LNP), and we determined whether anti-PEG antibodies could affect the antigen-specific immune response of mRNA-OVA-LNP vaccination in mice pretreated with PEG-modified liposomes to induce the production of anti-PEG antibodies. After intramuscular (i.m.) injection of the mRNA-LNP, the anti-PEG antibodies did not change the expression of protein or induction of cytokine and cellular immune response but did slightly increase the induction of antigen-specific antibodies. Furthermore, repeated mRNA-LNP i.m. injection induced the production of anti-PEG IgM and anti-PEG IgG. Our results suggest that mRNA-LNP induces the production of anti-PEG antibodies, but the priming of the antigen-specific immune response of mRNA-LNP vaccination is not notably affected by anti-PEG antibodies.

Spatial Measurement and Inhibition of Calpain Activity in Traumatic Brain Injury with an Activity-Based Nanotheranostic Platform.

Traumatic brain injury (TBI) is a major public health concern that can result in long-term neurological impairments. Calpain is a calcium-dependent cysteine protease that is activated within minutes after TBI, and sustained calpain activation is known to contribute to neurodegeneration and blood-brain barrier dysregulation. Based on its role in disease progression, calpain inhibition has been identified as a promising therapeutic target. Efforts to develop therapeutics for calpain inhibition would benefit from the ability to measure calpain activity with spatial precision within the injured tissue. In this work, we designed an activity-based nanotheranostic (ABNT) that can both sense and inhibit calpain activity in TBI. To sense calpain activity, we incorporated a peptide substrate of calpain flanked by a fluorophore/quencher pair. To inhibit calpain activity, we incorporated calpastatin peptide, an endogenous inhibitor of calpain. Both sensor and inhibitor peptides were scaffolded onto a polymeric nanoscaffold to create our ABNT. We show that in the presence of recombinant calpain, our ABNT construct is able to sense and inhibit calpain activity. In a mouse model of TBI, systemically administered ABNT can access perilesional brain tissue through passive accumulation and inhibit calpain activity in the cortex and hippocampus. In an analysis of cellular calpain activity, we observe the ABNT-mediated inhibition of calpain activity in neurons, endothelial cells, and microglia of the cortex. In a comparison of neuronal calpain activity by brain structure, we observe greater ABNT-mediated inhibition of calpain activity in cortical neurons compared to that in hippocampal neurons. Furthermore, we found that apoptosis was dependent on both calpain inhibition and brain structure. We present a theranostic platform that can be used to understand the regional and cell-specific therapeutic inhibition of calpain activity to help inform drug design for TBI.

Enhancement of immunity and disease resistance in Litopenaeus vannamei through injection of tyramine formulated with polyethylene glycol.

This study investigates the prolonged effect of immune disease resistance in Litopenaeus vannamei through the administration of tyramine (TA) formulated with polyethylene glycol (PEG). Facing the challenges of intensive farming, environmental stress, and global climate changes, innovative approaches to improve shrimp health are essential. The research focuses on the role of biogenic amines in stress response and immune regulation, demonstrating that TA, especially when combined with PEG, significantly prolongs immunity and resistance against Vibrio alginolyticus. The experimental design included administering TA, PEG, and TA-PEG, followed by evaluations of immunity, lactate and glucose levels, and immune-related gene expressions. Results showed notable prolonged effects in total hemocyte count, phenoloxidase activity, and phagocytic activity in the TA-PEG group, indicating enhanced immune activation period. Additionally, the expression of prophenoloxidase system-related genes was significantly upregulated in the TA-PEG group. Furthermore, the TA-PEG group exhibited a significantly higher survival rate in a susceptibility test against V. alginolyticus. The results of this study confirm that the combined use of PEG can effectively extend the immunostimulatory duration of TA.

Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Comparative study of the catalytic performance of physically mixed and sequentially utilized γ-alumina and zeolite in methanol-to-propylene reactions.

This study aimed to investigate the catalytic performance of H-ZSM-5 zeolite compared with physically mixed and sequentially used synthesized γ-alumina and zeolite in the methanol-to-propylene (MTP) reaction. A facile, green and cost-effective method was first applied to prepare a mesoporous γ-Al2O3 support using a combination of sol-gel and hydrothermal methods via a few consecutive steps. This process was carried out using aluminium nitrate and polyethylene glycol with different molecular weights as non-ionic surfactants. X-ray diffraction, transmission electon microscopy, thermogravimetric analysis, ammonia temperature programmed desorption and Brunauer-Emmett-Teller analysis were then used to characterize the prepared γ-Al2O3 catalyst. Afterwards, the catalytic activity of the commercial H-ZSM-5 zeolite (Si/Al = 200) and the effect of the presence of the γ-alumina physically mixed and unmixed with the zeolite were also researched in the MTP reaction. Accordingly, methanol conversion and product selectivity were monitored via gas chromatography. The physically mixed mesoporous γ-Al2O3 and H-ZSM-5 zeolite exhibited the highest catalytic activity in terms of both conversion and selectivity at 400°C. To our knowledge, this research represents the first documented use of γ-alumina and zeolite simultaneously as catalysts in the MTP reaction within the English literature. It is hoped that this work will offer valuable insights for advancing the development of catalytic systems in methanol conversion processes.

PEGylated ß-Cell-Targeting Exosomes from Mesenchymal Stem Cells Improve ß Cell Function and Quantity by Suppressing NRF2-Mediated Ferroptosis.

Background: The depletion of ß cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects ß cell function remain incompletely understood, and the limited ability of MSC-EXO to target ß cells and the short blood circulation time hampers its therapeutic effectiveness. Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a ß-cell-targeting aptamer and polyethylene glycol (PEG). The ß-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed. Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting ß cell mass via inhibiting nuclear factor erythroid 2-related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated ß-cell targeting. Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of ß cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy.

Pegylation enhances the anti-osteoporosis activity of acacetin in both ovariectomized and LPS-stimulated mice.

Osteoporosis is a condition of progressive bone loss attributable to excessive osteoclastic activity. Acacetin is a potential candidate for osteoporosis therapy because it specifically suppressing osteoclastic function. However, the application of acacetin was limited by its poor solubility and bad pharmacokinetic behavior. In current work, we examined whether PEGylation of acacetin enhances its anti-osteoporosis activity in ovariectomy-induced osteoporosis and LPS-induced osteolysis. In the current study, three types of PEGylated acacetin (PEG3-A, PEG4-A, PEG5-A) were tested for their effects on the solubility and anti-inflammatory activity of acacetin in vitro. PEG5-Acacetin was selected for further investigation as it demonstrated the strongest anti-inflammatory activity comparable to that of naked acacetin and other two PEGylated acacetin. PEGylation in PEG5-Acacetin increased maximum plasma concentration of acacetin by 620.77% in mice. Furthermore, PEG5-A showed a higher anti-osteoclastogenic capacity in vitro than that of naked acacetin. It was found that PEG5-A treatment in vivo mitigated lipopolysaccharide (LPS)- and ovariectomy (OVX)-induced bone loss in mice. More importantly, the in vivo efficiency of PEG5-Acacetin was significantly better than that of naked acacetin. In summary, PEGylated acacetin possesses a clean advantage over the naked acacetin and would be a potential candidate for the osteoporosis therapy.

Assessing anticancer properties of PEGylated platinum nanoparticles on human breast cancer cell lines usingin-vitroassays.

This study describes the in-vitro cytotoxic effects of PEG-400 (Polyethylene glycol-400)-capped platinum nanoparticles (PEGylated Pt NPs) on both normal and cancer cell lines. Structural characterization was carried out using x-ray diffraction and Raman spectroscopy with an average crystallite size 5.7 nm, and morphological assessment using Scanning electron microscopy (SEM) revealed the presence of spherical platinum nanoparticles. The results of energy-dispersive x-ray spectroscopy (EDX) showed a higher percentage fraction of platinum content by weight, along with carbon and oxygen, which are expected from the capping agent, confirming the purity of the platinum sample. The dynamic light scattering experiment revealed an average hydrodynamic diameter of 353.6 nm for the PEGylated Pt NPs. The cytotoxicity profile of PEGylated Pt NPs was assessed on a normal cell line (L929) and a breast cancer cell line (MCF-7) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results revealed an IC50of 79.18 µg ml-1on the cancer cell line and non-toxic behaviour on the normal cell line. In the dual staining apoptosis assay, it was observed that the mortality of cells cultured in conjunction with platinum nanoparticles intensified and the proliferative activity of MCF-7 cells gradually diminished over time in correlation with the increasing concentration of the PEGylated Pt NPs sample. Thein vitroDCFH-DA assay for oxidative stress assessment in nanoparticle-treated cells unveiled the mechanistic background of the anticancer activity of PEGylated platinum nanoparticles as ROS-assisted mitochondrial dysfunction.

Preparation and in vitro evaluation of pH and glutathione dual-responsive drug delivery system based on sodium carboxymethyl cellulose.

Stimuli-responsive drug delivery systems based on sodium carboxymethyl cellulose (NaCMC) for drug release encounter inherent challenges. In this research, a novel pH and glutathione (GSH) dual-responsive system, CPT-S-S-NaCMC@ZIF-8/SP-PEG, was constructed. Firstly, the prodrug CPT-S-S-OH was synthesized and combined with NaCMC to form GSH-responsive micelles CPT-S-S-NaCMC, significantly enhancing the drug loading and grafting rates to 63.79 % and 91.99 %, respectively. Subsequently, zinc ions and dimethylimidazole can be assembled into porous materials (ZIF-8) on the surface of the micelles. This system exhibits dual pH-GSH responsiveness and effectively reduces the drug release from 84.76 % to 28.71 % at pH = 7.4. Moreover, incorporating pH-responsive spiropyran (SP)-modified polyethylene glycol (PEG) can reduce drug leakage to 16.09 % at pH = 7.4 and exhibit good fluorescence intensity at 722 nm.

A novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion.

AIMS: Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects. MATERIALS AND METHODS: In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up. RESULTS: The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs. CONCLUSION: In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.

Polyethylene Glycol Misuse Causing Acute Renal Failure and Metabolic Acidosis Requiring Dialysis: A Case Report.

Laxative misuse is a well-known occurrence, most often identified in patients struggling with eating disorders. Polyethylene glycol (PEG) 3350 is a readily available, well-tolerated osmotic laxative. High doses of PEG 3350 may cause gastrointestinal upset, diarrhea, dehydration, and electrolyte imbalance, although systemic toxicity is infrequently reported. This case report highlights the exceedingly rare metabolic derangements associated with profound levels of protracted PEG misuse. A 60-year-old female presented to the emergency department with altered mental status. She was found to have acute renal failure (ARF), anion gap metabolic acidosis (AGMA), and rhabdomyolysis secondary to excessive PEG 3350 use, requiring continuous renal replacement therapy (CRRT). Renal function improved after three days of CRRT, and no alternative causes beyond PEG ingestion were found to account for her mental status changes or metabolic anomalies. This report illustrates the importance of considering osmotic laxative misuse in the setting of pre-renal and intrinsic renal failure.

Comparison of the Effect of Two Therapeutic Interventions for the Treatment of Chronic Constipation in Children With Cerebral Palsy: A Randomized Clinical Trial.

Objectives. Constipation is one of the most common gastrointestinal symptoms in children with neurological disorders. This study was performed to compare the therapeutic effect of polyethylene glycol (PEG) plus domperidone with PEG plus placebo in the treatment of chronic constipation in children with cerebral palsy. Methods. In this a double-blind clinical trial study was done on the children with cerebral palsy who had chronic constipation and was referred to Mohammad Kermanshahi hospital of Kermanshah city in the west of Iran. The participants were randomly divided into 2 groups with 2 therapies of PEG combined with domperidone (case group, n = 21) and PEG with placebo (control group, n = 21). The information was extracted from patients based on the checklist before and after treatment and the response to treatment in the 2 groups were determined and compared. The data were analyzed by T-test or Mann-Whitney U test to compare quantitative variables and Chi-square and Fisher's exact tests for comparing qualitative variables. Results. In both case and control groups, all Rome IV criteria for a diagnosis of chronic constipation except incontinence were significantly reduced after treatment. However, the successful response rate in the case group (PEG + domperidone) was 90.5%, while this rate was 61.9% in the control group. Conclusion. Based on the results of the present study, it seems that PEG plus domperidone had a positive effect on the treatment of children with cerebral palsy and chronic constipation.

Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients.

BACKGROUND AND AIMS: Information on effective bowel preparation (BP) methods for patients with constipation is limited. We recently reported the efficacy of 1 L polyethylene glycol plus ascorbic acid (PEG-Asc) combined with senna for BP; however, this regimen was insufficient in patients with constipation. We hypothesized that the addition of linaclotide, which is approved for the treatment of chronic constipation, to 1 L PEG-Asc would yield results superior to those of senna in patients with constipation. METHODS: This was a retrospective, single-center study that included outpatients with constipation who underwent BP prior to colonoscopy between March and December 2019 (receiving 1 L PEG-Asc with 24 mg senna) and between January and October 2020 (receiving 1 L PEG-Asc with 500 mg linaclotide). RESULTS: A total of 543 patients with constipation were included, of whom 269 received linaclotide and 274 received senna. The rate of inadequate BP was significantly lower (11% vs 20%, p < 0.01) and the adenoma detection rate was significantly higher (54% vs 45%, p = 0.04) in the linaclotide group than in the senna group. Multivariate analysis revealed that the linaclotide regimen significantly reduced the risk of inadequate BP (odds ratio = 0.36, 95% confidence interval = 0.21-0.60, p < 0.01). CONCLUSIONS: The linaclotide regimen significantly increased BP efficacy and the adenoma detection rate compared with the senna regimen without reducing tolerability and is therefore a promising new option for BP in patients with constipation.

COVID-19 vaccines: anaphylaxis and anxiety : A case study from an allergy unit.

BACKGROUND: Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was one crucial element to overcome the coronavirus disease 2019 (COVID-19) pandemic. Even though anaphylaxis to vaccines is rare, 47 patients came to the Allergy Unit at the University Hospital Graz, Austria, reporting immediate anaphylactoid symptoms after administration of COVID-19 vaccines. In addition, 29 patients with known drug-induced anaphylaxis wanted to be tested for a possible sensitization against COVID-19 vaccines or excipients, such as polyethylene glycol (PEG) or polysorbate 80 (PS80) before the first COVID-19 vaccination. Skin prick tests and intradermal tests were performed in all 76 patients, mostly using PEG 2000, and/or PS80. Skin prick tests with COVID-19 vaccines were performed depending on availability. OBJECTIVE: Our aim was to characterize this patient cohort in terms of patients' anaphylactoid responses, their willingness to future vaccinations against SARS-Cov­2, and reasons for their decision. METHODS: We developed a questionnaire and analyzed 34 completed copies. RESULTS: Of the 47 patients with anaphylactoid reactions to COVID-19 vaccination, most were female (40 female/7 male). The skin tests, even when performed with the respective COVID-19 vaccine, were negative in all but one patient. Most patients who experienced anaphylactoid reactions after a COVID-19 vaccination, did not want another COVID-19 vaccination at the time of answering the questionnaire because of anxiety for another anaphylactoid response at the next shot. Premedication with antihistamines significantly lowered (n = 74 vaccinations) the severity of anaphylactoid responses after COVID-19 vaccinations. CONCLUSION: Anxiety about another anaphylactoid episode hinders patients to be vaccinated against SARS-CoV­2 again. Premedication with antihistamines and collaboration of allergologists with psychologists might lower the risk of an anaphylactic/anaphylactoid response as well anxiety in drug-induced anaphylactic patients.