Tolerability Of Polyethylene Glycol Research Articles

Rhizobial and passenger endophytes alleviates moisture stress in groundnut (Arachis hypogaea)

Moisture stress poses a significant threat to global agriculture, compromising crop yields and food security. In the quest for sustainable solutions, endophytic microorganisms have emerged as promising candidates for enhancing plant resilience to drought. The study's primary goal was to analyse the significance of bacterial endophytes, both rhizobial and passenger endophytes, in alleviating the effects of moisture stress. Here, PEG 6000 was used to test the drought endurance of the ten identified rhizobial and passenger endophytes. Rhizobium pusense S6R2, Enterobacter cloacae S23 and Bacillus tequilensis NBB13 were selected as best performing endophytes as they showed high tolerance of poly ethylene glycol (PEG) and maximum plant growth promoting traits like Indole Acetic Acid, exopolysaccharide production, biofilm formation, 1-aminocyclopropane1-carboxylate (ACC) deaminase activity, siderophore, zinc and phosphorous solubilisation even in PEG induced moisture stress condition. Metabolite analysis revealed that twenty-four significant compounds mostly belong to fatty acyls, amino acids, peptides, polyketides, and benzenoids were found in the root exudates of groundnut treated with endophytes. The best-performing endophytes were used in a pot culture experiment, with groundnut as the test crop. The current study found that co-inoculation of Rhizobium pusense S6R2 and Enterobacter cloacae S23 significantly increased nodule number, growth, photosynthetic pigment, anti-oxidant enzymes, and osmolyte under moisture stressed conditions when compared to other treatments. As a result, co-inoculation of Rhizobium and entophytic bacteria may be recommended as a bio-inoculant for groundnut for moisture stress alleviation after confirming the results in field evaluation.

Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in patients with chronic constipation

BackgroundChronic constipation is a significant factor in poor bowel preparation for colonoscopy. Macrogol 4000 plus electrolytes (Movicol, EA Pharma, Tokyo, Japan), containing polyethylene glycol (PEG) and electrolytes, have been used recently to treat patients with constipation. However, prospective studies on the use of macrogol 4000 for bowel cleansing for colonoscopy are lacking. This study aimed to investigate the efficacy and safety of macrogol 4000 in addition to PEG administered in patients with chronic constipation.MethodsThis single-center, single-arm prospective study enrolled patients with chronic constipation who were scheduled to undergo colonoscopy. The primary endpoint was the proportion of good bowel preparation assessed using the Boston bowel preparation scale (BBPS) (6 or more points). The secondary endpoints were the time from when pPEG (MoviPrep, EA Pharma, Tokyo, Japan) was taken until colonoscopy could be started, amount of PEG taken, number of defecations, whether additional PEG doses were taken, and adverse events. Endoscopy-related endpoints included cecal intubation rate, insertion time, observation time, adenoma detection rate (ADR), and polyp detection rate (PDR). The tolerability of PEG and macrogol 4000 was assessed using a questionnaire.ResultsForty patients were included in the analysis. The median BBPS was 7 (range 3–9) and ≥ 6 points in 37 cases (92.5%). The median time until colonoscopy can be started was 210 min (90–360 min), the median volume of PEG taken was 1500 mL (1000–2000 mL), and the median number of defecations was 7 (3–20). No adverse events were observed. Fourteen patients required an additional dose of PEG. Cecal intubation was achieved in all cases, the median insertion time was 6.0 min (range 2.3–22 min), and the median observation time was 8.8 min (range 4.0–16.0 min). The ADR and PDR were 60.0% and 75.0%, respectively. A proportion of patients rated the tolerability of macrogol 4000 and PEG as 95.0% and 50.0%, respectively.ConclusionsIntake of macrogol 4000 in addition to PEG is effective and safe for colonoscopy in patients with chronic constipation.Clinical trial registration statement This study was registered in the UMIN-CTR database (UMIN-ID000038315).

Split dose bowel preparation before colonoscopy of PEG (Nulytely) in comparison to routine single dose bowel preparation.

Background:The aim of this study was to compare the efficacy and tolerability of polyethylene glycol (PEG) in single- or split-dose regimens for colonoscopy bowel preparation.Methods:This is a prospective, randomized, endoscopist blinded, single-center study, that included adult patients who underwent colonoscopy during the period from December 2017 to October 2018. Two groups were enrolled in the same period: One group used 4 L of PEG (Nulytely) in a single-dose preparation, administered a day before the procedure, and the other group received a split-dose regimen of 2 L PEG (Nulytely), given a day before the procedure and 2 L on the day of the procedure in the early morning. The Boston Bowel Preparation Scale (BBPS) was used for bowel preparation adequacy; scales 0 and 1 were considered inadequate, and scales 2 and 3 were considered adequate preparation.Results:Two hundred and forty patients were enrolled, 120 (50%) using the split-dose regimen and 120 (50%) using the single-dose regimen, for bowel preparation. Males constituted 51.6% of the study cohort. In the single-dose group, 62.5% achieved adequate bowel preparation compared to 89.2% in the split-dose group (p< 0.001). In addition, polyp detection in the split-dose group was 23.3% in comparison to 10.8% in the single-dose group (P = 0.016). We also found hypertension and diabetes as significant predictors of bowel preparation inadequacy, while sex and age were not related to bowel preparation adequacy.Conclusions:Split-dose bowel preparation for colonoscopy with PEG (Nulytely) is better than routine single-dose, in terms of adequate bowel preparation and polyp detection.

Effect of gangliosides on structure and integrity of polyethylene glycol (PEG)-stabilized liposomes

The in vivo efficacy and tolerance of polyethylene glycol (PEG)-decorated drug nanocarriers, such as liposomes, is compromised bytheir tendency to induce the generation of PEG-specific immunoglobulin M (IgM) antibodies. Recently, a number of independent studies have reported on an attenuated anti-PEG immune response upon incorporation of gangliosides in the membrane of PEGylated liposomes.In the present study we investigate the effect of gangliosides on the self-assembled structures found in lipid dispersions based on hydrogenated egg phosphatidylcholine (HEPC), cholesterol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG(2000)). Results from cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) investigations show that gangliosides promote structural transitions from liposomes to bilayer disks. In case of samples comprising 5 mol% PEG-conjugated lipids (PEG-lipid), inclusion of 2.5 mol% ganglioside (porcine ganglioside extract) results in the presence of a small but significant amount of disks. With increasing ganglioside content the population of disks grows at the expense of the liposomes. Comparative investigations using isolated ganglioside components reveal that disialoganglioside GD1a is more potent than monosialoganglioside GM1 in promoting disk formation. Experiments involving liposome encapsulated carboxyfluorescein confirm that the ganglioside-induced structural transformations have a detrimental effect on the total entrapped aqueous volume of the samples. The reported coexistence of liposomes and bilayer disks may if overlooked have important implications for the therapeutic efficacy and immunogenicity of ganglioside-supplemented liposomal formulations.

PEG vs. sennosides for opioid-induced constipation in cancer care.

This randomized double-blind, double-dummy, 2-treatment, 2-period crossover study aimed to compare the efficacy and tolerability of polyethylene glycol (PEG) and sennosides in ambulatory cancer patients with opioid-induced constipation. Outpatients ≥ 18years old with cancer, at risk of or already experiencing opioid-induced constipation, were randomly assigned to begin a standard bowel protocol of escalating doses of sennosides or PEG, plus a dummy preparation. After 3weeks, the patients switched to the alternate active product and dummy preparation. Constipation was assessed using the revised Victoria Bowel Performance Scale (rBPS) at the end of each of the 2 consecutive 21-day study periods for the number of days with a satisfactory bowel movement, the time in days to goal rBPS (G), and the treatment preference of each patient. Seventy patients were recruited, with 42 completing their first treatment period and 28 completing both treatment periods. For the typical patient, the expected number of days with a satisfactory bowel movement per days of treatment was found to be 1.21 times higher on PEG than on sennosides in a particular period (95% credible interval 0.96 to 1.55). Patients taking PEG were 1.47 times more likely to reach a rBPS of G before patients taking sennosides in the first period (95% confidence interval 0.74 to 2.94). There was no evidence of a difference in patient preference between laxatives. Our study found weak evidence that PEG is superior to sennosides with respect to overall effectiveness in cancer patients with opioid-induced constipation.

Effectiveness of filgrastim and polyethylene glycol-filgrastim in the treatment of postchemotherapy neutropenia in children: Phase I clinical trial

Abstract Background: One of the most common side effects of chemotherapy in cancer patients is neutropenia that can result in hospitalization. The purpose of this study was to evaluate the efficacy and tolerability of polyethylene glycol (PEG)-filgrastim compared with filgrastim in the recovery of neutropenia. Methods: This study was a Phase I clinical trial conducted among patients with acute lymphoblastic leukemia aged &lt;16 years who were referred to the Ali Asghar Hospital, Tehran, Iran, from April 2012 until October 2013. Eleven patients were selected, and filgrastim and PEG-filgrastim were injected subcutaneously at a dose of 5–10 μg/kg/day for 7 days and 100 μg/kg as a single dose, respectively. Absolute neutrophil count (ANC) was checked 7 days after the last injection in the two groups. Results: The mean age of the patients was 8.82 ± 4.36 years (3–15 years). Six boys (54.5%) and five girls (45.5%) participated in the study. ANC increase among patients treated with PEG-filgrastim or filgrastim was analyzed separately, and the results showed statistically significant differences between the study groups (P = 0.038). Conclusions: According to the findings, it can be concluded that the PEG-filgrastim is better than filgrastim alone to improve neutropenia induced by chemotherapy in patients with acute lymphoblastic leukemia.

Polyethylene Glycols with or without Electrolytes for Constipation in Children: A Network Meta-Analysis

Background: Polyethylene glycol laxatives are the cornerstone of the management of constipation in children. They are available with and without electrolytes.Aims: The aims of this network meta-analysis (NMA) were to assess the relative efficacy, safety and tolerability of polyethylene glycol with (PEG+E) or without electrolytes (PEG) in the management of constipation in children.Methods: A systematic review and NMA was undertaken to identify and analyse all published randomised controlled clinical trials of polyethylene glycol in children with constipation. Text word searches were carried out using MEDLINE, MEDLINE in Progress, EMBASE, Cochrane Database and Systematic Reviews databases covering inception to April 2015. The primary efficacy analysis was the mean number of bowel movements per week. Secondary endpoints assessed safety, tolerability and compliance.Results: 15 studies (involving 1,384 patients) were included in the NMA. PEG and PEG+E are both more effective than placebo, increasing the mean number of bowel movements per week by 2.3 (95% Crl 0.3, 4.4) and 2.2 (95% Crl 0.1, 4.7) respectively. Direct comparison of PEG+E with PEG identified no differences in efficacy, safety, or tolerability, with the exception of one study demonstrating better tolerability with PEG. Compared to PEG+E, PEG was easier to take, with a trend towards improved compliance.Conclusion: This NMA provides no evidence to support the clinical utility of added electrolytes to polyethylene glycol in the management of constipation in children. PEG alone is as effective as PEG+E and both therapies are well tolerated. This analysis supports the ongoing use of polyethylene glycol as a first-line treatment of constipation in children. Formulations without electrolytes should be considered first to optimize patient acceptability and adherence.

Solvent-based formulations for intravenous mouse pharmacokinetic studies: tolerability and recommended solvent dose limits

1. Modern high-throughput small molecule drug discovery requires rapid screening of the pharmacokinetic parameters of multiple candidate molecules in parallel. The mouse is often used for such screening, as are solvent-based intravenous formulations. Despite this, the intravenous toxicity of many commonly used solvents is unknown. The purpose of this investigation is to establish recommended no-observed-effect level (NOEL) and maximum tolerated dose (MTD) for several commonly used intravenous solvents in the CD-1 mouse.2. The acute tolerability of polyethylene glycol 400, N-methylpyrrolidone, dimethyl sulfoxide, ethanol, dimethylacetamide and propylene glycol was established, along with combinations of polyethylene glycol 400 and/or ethanol and DMSO. Based on these data, an acute NOEL and recommended MTD is reported for each solvent or solvent combination.3. These data can guide the use of these solvents to support single-dose intravenous pharmacokinetic studies in mice. By establishing a defined dose tolerability range for the most commonly used intravenous solvents, undue pain and distress in animals can be avoided while maximizing the generation of critical pharmacokinetic data for project teams.

Clinical trial: 2‐L polyethylene glycol‐based lavage solutions for colonoscopy preparation – a randomized, single‐blind study of two formulations

The 2-L polyethylene glycol (PEG) lavage solutions provide efficacy similar to that of standard 4-L PEG formulations in spite of the reduced volume. The comparative efficacy and tolerability of two formulations of 2-L PEG solution remain unknown. To assess the efficacy, safety and tolerability of PEG + Bis compared with PEG + Asc, and to study the effect of bowel cleansing quality on adenoma detection rates. Patients were randomized to receive either 2-L PEG with ascorbic acid (PEG + Asc) or 2-L PEG plus bisacodyl 10 mg (PEG + Bis). The primary endpoint was overall colon cleansing score, assessed by blinded investigators using a validated four-point scale. Secondary endpoints included adenoma detection rate, patient tolerability and compliance and adverse events. Fifty-two patients received PEG + Asc and 55 patients received PEG + Bis. Overall colon cleansing scores (+/-s.d.) were 1.40 +/- 0.69 and 1.75 +/- 0.70 (P < 0.003) in the PEG + Asc and PEG + Bis groups, respectively. Excellent and good ratings were recorded in 69% and 23% receiving PEG + Asc compared to 38% and 51% (P = 0.01) of patients receiving PEG + Bis. More adenomas were detected in colonoscopies performed with PEG + Asc (39%) than in those performed with PEG + Bis (20%) (P = 0.04). Patient tolerability and safety were similar with both preparations. The use of PEG + Asc resulted in better colon cleansing and higher adenoma detection rates compared with PEG + Bis.

Long-term efficacy and cost-effectiveness of polyethylene glycol 3350 plus electrolytes in chronic constipation: a retrospective study in a disabled population

ABSTRACTObjectives: The efficacy and safety of treatments for constipation in severely intellectually disabled patients and their associated cost-effectiveness are an underinvestigated area of clinical practice. Aiming to address this, the objectives of the study were to evaluate the efficacy and tolerability of polyethylene glycol 3350 plus electrolytes (Movicol; PEG+E) by comparing clinical data collected before and after its introduction to a stable population of residents of a mental health care, long-stay institution. The study also attempted an economic evaluation of the use of PEG+E in this setting.* Movicol is a registered trademark of NorgineResearch design and methods: This was a retrospective study of 54/66 severely intellectually and physically disabled residents of a specialist unit at La Milétrie University Hospital, Poitiers, France, who suffered regularly from constipation. A total of 54 residents were treated with PEG+E (1–3 sachets a day) for 24 months. The number of stools, episodes of diarrhoea (defined as frequent stools, not necessarily watery), body weights and blood biochemistry were recorded. Data were compared with those recorded during the 21 months preceding the introduction of PEG+E for 16/54 residents who had been treated regularly with a range of other interventions for the relief of constipation. The monthly use and costs of laxatives, enemas and suppositories was obtained from hospital pharmacy records, and the total hospital costs before and after the introduction of PEG+E treatment was calculated.Results: The mean (± standard deviation) number of stools per patient per month was significantly greater following the introduction of PEG+E (24.9 ± 6.3) compared to before its use (12.4 ± 3.4) ( p < 0.001). The mean (± standard deviation) monthly number of episodes of diarrhoea per patient before and after the introduction of PEG+E was 0.1 ± 0.1 and 6.3 ± 2.9, respectively ( p < 0.001). Treatment with PEG+E was not associated with adverse effects on body weight or blood biochemistry values. Introduction of PEG+E and its increasing use reduced the total hospital medical ward expenditure on laxatives from 3788 to 1767 Euros per month.Conclusions: PEG+E is effective in the clinical management of constipation in an institutional setting. Furthermore, long-term intensive therapy with PEG+E was not associated with adverse effects on body weight or blood biochemistry values. Although the time periods over which the economic data and the efficacy and safety data were collected did not directly correspond, this study indicates that use of PEG+E in the management of constipation in people with severe intellectual disability may be cost-effective, reducing hospital laxative costs.

Highly Effective Oral Therapy (Polyethylene Glycol/Electrolyte Solution) for Faecal Impaction and Severe Constipation

Objective: To investigate the efficacy and tolerability of polyethylene glycol/ electrolyte solution (Movicol®, Norgine Ltd) therapy in patients with faecal impaction and severe constipation.