Administration Of Polyethylene Glycol Research Articles

Study of Anticonvulsant effect of Simvastatin in Maximal Electroshock and Pentylenetetrazole Induced Seizure Model In Albino Mice

Epilepsy is a common neurological condition affecting people of all ages and both sexes. Most of the currently used antiepileptic drugs have neurotoxic and teratogenic effects. There are scanty reports of anticonvulsant activity with statins. The present study was undertaken to evaluate the anticonvulsant effect of simvastatin using MES and PTZ models in mice and compare it with the standard drugs phenytoin and diazepam respectively.64 albino mice of either sex weighing 25-35g were divided into 8 groups of 8 mice each – 4 group each for MES and PTZ model. In MES model, seizures were induced via trans auricular electrodes with a current of 80mA for 0.2 second. Each mouse was pretreated with drugs 30 minutes before in both models. The different groups 1 to 4 were administered polyethylene glycol (0.5ml/Kg), phenytoin (20mg/kg), simvastatin (10mg/Kg) and simvastatin (20mg/Kg) respectively. In PTZ model, seizures were induced by giving PTZ 80mg/Kg. The different groups 5 to 8 were administered polyethylene glycol (0.5ml/Kg), diazepam (2mg/kg), simvastatin (10mg/Kg) and simvastatin (20mg/Kg) respectively. Statistical analysis was doneby ANOVA followed by Tukey’s post hoc analysis for group wise comparison. Results indicated that the anticonvulsant effect of simvastatin (10 and 20mg/Kg) was comparable to phenytoin in the MES model. In the PTZ model, simvastatin (10mg/Kg) produced a reduction in seizure duration but did not provide seizure protection as compared to that of the diazepam. The present study demonstrated the anticonvulsant effect of simvastatin. Further studies may explore the potential of this as an add-on drug in patients with dyslipidemia and epilepsy.

Magnetic Resonance Enterography Reinvented: Exploring the Potential of a New Natural Beverage as an Alternative to Polyethylene Glycol Solution

The aim of the present study was to test a new oral contrast medium composed of natural components for the magnetic resonance (MR) imaging of small bowel diseases. Between January 2018 and June 2019, 35 patients affected by ileocolic Crohn’s disease (CD) were enrolled in the present study. Each patient underwent two sequential MR enterographies, first with the standard polyethylene glycol (PEG) water solution and, after 3 weeks, with the new natural beverage designed by our team. At the end of the administration of each oral contrast, a satisfaction survey was given to the patients to assess the palatability of both beverages. The intestinal distention and the quality of images were evaluated by two expert radiologists for both studies and the interreader agreement was calculated. According to the satisfaction questionnaire, 97.1% of patients expressed positive judgments regarding the natural beverage (71.4% very good and 25.7% good) whereas only 8.6% of them appreciated the PEG water solution (8.6% good) (p = 0.0001). The degree of intestinal distention was excellent and good in 97.1% of patients after the administration of PEG and in 94.3% of the patients after the administration of the natural beverage, without significant differences between the two products and with almost perfect (k = 0.821) and substantial (k = 0.754) inter-observer variability, respectively. No statistical differences were observed between the two expert radiologists regarding the evaluation of the imaging quality; in particular, they were considered good and excellent in 100% of patients after the administration of PEG water solution and in 97.2% of those who took the natural beverage, with substantial (k = 0.618) and almost perfect (k = 0.858) inter-observer variability, respectively. The new natural beverage demonstrated the same intestinal distension and excellent image quality compared to the synthetic standard oral contrast administered during MRE for small bowel diseases, proving to be a valid alternative with better palatability.

Effect of Oral Administration of Polyethylene Glycol 400 on Gut Microbiota Composition and Diet-Induced Obesity in Mice.

Polyethylene glycol (PEG) is a commonly used dispersant for oral administration of hydrophobic agents. PEG is partly absorbed in the small intestine, and the unabsorbed fraction reaches the large intestine; thus, oral administration of PEG may impact the gut microbial community. However, to the best of our knowledge, no study evaluated the effects of PEG on gut commensal bacteria. Herein, we aimed to determine whether oral administration of PEG modifies the gut microbiota. Administration of PEG400 and PEG4000 altered gut microbial diversity in a concentration-dependent manner. Taxonomic analysis revealed that Akkermansia muciniphila and particularly Parabacteroides goldsteinii were overrepresented in mice administered with 40% PEG. PEG400 administration ameliorated the high-fat diet (HFD)-induced obesity and adipose tissue inflammation. Fecal microbiome transplantation from PEG400-administered donors counteracted the HFD-induced body and epididymal adipose tissue weight gain, indicating that PEG400-associated bacteria are responsible for the anti-obesity effect. Conversely, carboxymethyl cellulose, also used as a dispersant, did not affect the abundance of these two bacterial species or HFD-induced obesity. In conclusion, we demonstrated that oral administration of a high concentration of PEG400 (40%) alters the gut microbiota composition and ameliorates HFD-induced obesity.

Intravenous Polyethylene Glycol Alleviates Intestinal Ischemia-Reperfusion Injury in a Rodent Model

Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.

Efficacy of morning-only dose compared with split-dose polyethylene glycol electrolyte solution in bowel cleansing for afternoon colonoscopy

Introduction: The efficacy of colonoscopy in detecting abnormalities within the colon is highly dependent on the adequacy of the bowel preparation. The objective of this study was to compare the efficacy and tolerability of morning only dose vs split-dose administration of polyethylene glycol (PEG) solution for colon cleansing in patients undergoing afternoon colonoscopy.
 Method: This was a comparative study conducted in Department of Medicine, Patan Academy of Health Sciences (PAHS), Patan Hospital, Nepal from November 2021 to June 2022. The ethical clearance was obtained from the Institutional Review Committee. Informed consent was taken from the patients. Patients aged >18 y undergoing elective colonoscopy were randomly assigned to one of the two bowel preparation regimens- morning only or split-dose of PEG. The adequacy of bowel preparation was assessed by the endoscopist using Boston Bowel Preparation scale. Preparation to colonoscopy (PC) interval, adverse events and risk factors for poor bowel preparations were noted.
 Result: In this study, 110 patients were included in the final analysis- 55 received morning only regimen and 55 received split-dose. Mean Boston bowel preparation scales of Morning only and Split-dose regimen were 7.60 and 7.09 respectively (p= 0.019). Split-dose group had significant sleep disturbances compared to Morning only regimen (p< 0.001), whereas nausea occurred significantly more often in Morning only regimen (p=0.012). Preparation to colonoscopy interval between 4-6 hours resulted in better bowel cleansing compared to PC interval of greater than 6 hours.
 Conclusion: Morning-only bowel preparation is more effective than Split-dose for achieving adequate colon cleansing for afternoon colonoscopy.

Parametric MRI Detects Aristolochic Acid Induced Acute Kidney Injury.

Exposure to aristolochic acid (AA) is of increased concern due to carcinogenic and nephrotoxic effects, and incidence of aristolochic acid nephropathy (AAN) is increasing. This study characterizes renal alterations during the acute phase of AAN using parametric magnetic resonance imaging (MRI). An AAN and a control group of male Wistar rats received administration of aristolochic acid I (AAI) and polyethylene glycol (PEG), respectively, for six days. Both groups underwent MRI before and 2, 4 and 6 days after AAI or PEG administration. T2 relaxation times and apparent diffusion coefficients (ADCs) were determined for four renal layers. Serum creatinine levels (sCr) and blood urea nitrogen (BUN) were measured. Tubular injury scores (TIS) were evaluated based on histologic findings. Increased T2 values were detected since day 2 in the AAN group, but decreased ADCs and increased sCr levels and BUN were not detected until day 4. Significant linear correlations were observed between T2 of the cortex and the outer stripe of outer medulla and TIS. Our results demonstrate that parametric MRI facilitates early detection of renal injury induced by AAI in a rat model. T2 mapping may be a valuable tool for assessing kidney injury during the acute phase of AAN.

Comparison of Same Day Polyethylene Glycol Regimen Vs Split Dose Polyethylene Glycol Regimen for Colonoscopy

Colonoscopy is a procedure which depends upon the quality of bowel preparation. Polyethylene glycol(PEG) is commonly used laxative for bowel preparation .The method of PEG administration affects the quality of bowel preparation. We designed this single-blinded randomized controlled trial to evaluate same day PEG regime vs split dose PEG regime in patients undergoing colonoscopy. METHOD: Total of 156 patients taken for the examination. They were divided randomly in two groups A & B. The patients in the group A (same day group) took 2 L of PEG between 6:00 AM and 8:00 AM on the same day of colonoscopy. The patients in the other group B ( split dose group ) took 1L of PEG between 6:00 PM and 8:00 PM on the preceding day and another liter between 6:00 AM and 8:00 AM on the day of colonoscopy. These patients had to stay in hospital for about 24 hours.The accuracy of preparation was assessed on Boston Bowel Preparation Scale (BBPS). A sum total of ≤ 5 points shows poor bowel preparation & ≥ 8 shows very good bowel preparation. Side effects were recorded by asking symptoms of nausea ,vomiting ,abdominal pain & bloating. Results: In same day dose group, 62 patients were having BPPS preparation score of >8 . While in second split dose group 64 patients were having BPPS preparation score >8. Chi square test revealed that there was no significant difference in BPPS score between both groups. However there was significant difference in patient satisfaction and willingness to repeat the same procedure between both groups. . Group A same dose regime were more satisfied & willing to repeat the procedure. They reported less interference in their sleep . Conclusion: Same- day morning PEG regime should be used which is more easy & tolerable for our patients population and its efficacy is same as other regimes for adequate bowel preparation.

S363 Successful Treatment of Distal Intestinal Obstruction Syndrome With N-acetylcysteine and Polyethylene Glycol via Colonoscopy

Introduction: Cystic fibrosis (CF) can lead to obstructive gastrointestinal disease, such as meconium ileus in children and distal intestinal obstruction syndrome (DIOS) in adults. DIOS is characterized by the accumulation of inspissated stool and viscous secretions in the terminal ileum and proximal colon, leading to complete or incomplete obstruction. Treatment strategies for DIOS are still essentially empirical as there are no randomized controlled trials to guide therapy. We describe a case of a CF patient with DIOS successfully treated with 4% N-acetylcysteine (NAC) and polyethylene glycol (PEG) administered via colonoscopy. Case Description/Methods: A 46-year-old woman with cystic fibrosis and prior episodes of DIOS presented with several days of abdominal pain and constipation. On exam, her abdomen was distended and diffusely tender to palpation. Abdominal CT showed extensive debris in the distal small bowel with resultant dilation proximally, thickening at the terminal ileum, and a decompressed colon (Fig A). She was initially managed with frequent enemas and oral laxatives including Lubiprostone and PEG via nasogastric tube. Her symptoms worsened and she was taken for urgent colonoscopy. With the patient in supine position, the colonoscope was meticulously advanced to the cecum, traversing several matted, mucoid-adherent folds (Fig B). A mucoid plug was seen extending from the ileocecal (Fig B) valve to the walls of the cecum (Fig C). The mucoid plug was injected with 4% NAC and PEG. The scope was then advanced into the terminal ileum approximately 20 cm to the proximal end of a large, actively dissolving fecalith with administration of NAC and PEG. A CRE 8-9-10 mm balloon was used to sweep the stool from the distal ileum. Following this maneuver, peristalsis was observed with inspissated stool emanating from the distal ileum towards the IC valve. Discussion: Optimal management of DIOS in CF patients remains a challenge. Although most cases are relieved with conservative treatments, select patients will need surgery, which is associated with a higher peri- and postoperative morbidity. However, the administration of 4% N-acetylcysteine and polyethylene glycol via colonoscopy offers a viable remedy that may obviate the need for surgery. Watch the video at https://tinyurl.com/ACGAbstractS363AFigure 1.: (A) Abdominal CT showing extensive debris in the distal small bowel. (B) Matted, mucoid-adherent folds in the colon. (C) A mucoid plug extending from the ileocecal valve to the walls of the cecum.

Mucus Penetrating and Cell-Binding Polyzwitterionic Micelles as Potent Oral Nanomedicine for Cancer Drug Delivery.

Orally administrable anticancer nanomedicines are highly desirable due to their easy and repeatable administration, but are not yet feasible because the current nanomedicine cannot simultaneously overcome the strong mucus and villi barriers and thus have very low bioavailability (BA). Herein, this work presents the first polymeric micelle capable of fast mucus permeation and villi absorption and delivering paclitaxel (PTX) efficiently to tumors with therapeutic efficacy even better than intravenously administered polyethylene glycol based counterpart or free PTX. Poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OPDEA), a water-soluble polyzwitterion, is highly nonfouling to proteins and other biomacromolecules such as mucin but can weakly bind to phospholipids. Therefore, the micelle of its block copolymer with poly(ε-caprolactone) (OPDEA-PCL) can efficiently permeate through the viscous mucus and bind to villi, which triggers transcytosis-mediated transepithelial transport into blood circulation for tumor accumulation. The orally administered micelles deliver PTX to tumors, efficiently inhibiting the growth of HepG2 and patient-derived hepatocellular carcinoma xenografts and triple-negative breast tumors. These results demonstrate that OPDEA-based micelles may serve as an efficient oral nanomedicine for delivering other small molecules or even large molecules.

AVP-eGFP was significantly upregulated by hypovolemia in the parvocellular division of the paraventricular nucleus in the transgenic rats.

Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.

Use of a polyethylene glycol solution for the management of sand impaction in three dogs

AbstractThree dogs were hospitalized for management of acute gastrointestinal signs secondary to sand impaction. Hospitalized care with administration of a polyethylene glycol (PEG) solution via nasogastric tube. Variable PEG solution doses were used in these dogs (range 72–109 ml/kg). All patients tolerated PEG administration without adverse effects. Two dogs had additional radiographs performed, consistent with radiographic improvement of impaction. Each dog had marked clinical improvement and was successfully discharged from the hospital.

Pre-treatment with high molecular weight free PEG effectively suppresses anti-PEG antibody induction by PEG-liposomes in mice

Immune responses against polyethylene glycol (PEG) can lead to the rapid clearance of PEGylated drugs and are associated with increased risk of serious adverse events such as infusion reactions and anaphylaxis. Although select PEGylated therapeutics can induce anti-PEG antibodies (APA), there is currently no readily deployable strategy to mitigate their negative effects. Given the large number of PEGylated therapeutics that are either FDA-approved or in clinical development, methods that suppress APA induction to ensure the safety and efficacy of PEGylated drugs in patients would be a valuable clinical tool. We previously showed that infusion of high molecular weight (MW) free PEG can safely and effectively restore the circulation of PEG liposomes in animals with high pre-existing titers of APA, without stimulating additional APA production. Here, we explored the effectiveness of prophylaxis with free PEG or tolerogenic PEGylated liposomes as a strategy to reduce the amount of APA induced by subsequently administered PEGylated liposomes. Surprisingly, we found that a single administration of free PEG alone was capable of markedly reducing the APA response to PEG-liposomes for ~2 months; the effectiveness was comparable to, and frequently exceeded, interventions with different tolerogenic PEG-liposomes. These results support further investigations of free PEG prophylaxis as a potential strategy to ameliorate the APA response to sensitizing PEGylated therapeutics.

Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways

Abstract Objective In this study, possible protective effects of protocatechuic acid (PCA) against experimentally-induced acute renal ischemia/reperfusion (I/R) damage in rats, on matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and the associated signal transduction pathways were investigated. Methods A total of 3–4 month-old, 200–250 g Sprague Dawley rats were divided into groups of five (n=7). A right kidney nephrectomy surgery was conducted to all groups under anesthesia. Rats were administered polyethylene glycol 1 h prior to ischemia (Group I, II) and PCA (Group III, IV, V) intraperitoneally. Forty five minutes before the ischemia during 24 h reperfusion on all rats except those in Group I. At the end of the experiment, blood urea nitrogen (BUN), creatinine values and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme levels were investigated in blood serum. MMP-2 and MMP-9 gene expression levels were determined by RT-PCR, and p38 and p-p38 protein expression levels Western blotting method. Renal tissue was examined histologically and immunohistochemically. Results It is assumed that 80 and 120 mg/kg of PCA might have a protective effect against oxidative stress damage caused by renal I/R. Conclusion In our study, PCA has been shown to modulate the increased expression of MMP-2 and MMP-9 mRNA along with increased oxidative stress during renal I/R, as well as oxidative damage-induced p38 protein expression. It was determined that particularly 120 mg kg−1 PCA reduced the renal I/R injury at a rate of 35–45%.

Oxytocin-monomeric red fluorescent protein 1 synthesis in the hypothalamus under osmotic challenge and acute hypovolemia in a transgenic rat line.

We generated a transgenic rat line that expresses oxytocin (OXT)‐monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos‐like immunoreactivity (co‐expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN‐ and PEG‐treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia.

Feeding of carob (Ceratonia siliqua) to sheep infected with gastrointestinal nematodes reduces faecal egg counts and worm fecundity

The present study explored the anthelmintic effects of condensed tannins (CT) in carob (Ceratonia siliqua) pods fed to sheep against gastrointestinal nematodes. Three independent in vivo trials tested whether i) carob pod (CaBP)-containing feed had an anthelmintic effect and if yes, which was the optimal concentration in the diet; ii) whether this effect could be attributed to tannins through the polyethylene glycol (PEG) test and iii) whether there were any synergistic effects when combined with another tannin-containing feed (e.g. sainfoin). In all trials 6-month old nematode-naive lambs, experimentally infected with both Haemonchus contortus and Trichostrongylus colubriformis, were used. Faecal egg counts (FEC) were performed regularly and at the end of each trial adult worm counts (AWC) and female worm fecundity were recorded. In trial 1, 35 lambs (five groups of seven lambs) were fed different CaBP concentrations ranging from 0% to 12 % w/w. FEC declined up to 39.2 % only in the group fed with 12 %CaBP, while a declining trend (P < 0.06) was demonstrated for the AWC of T. colubriformis, which was associated with the increasing concentration of CaBP in feed. Female worm fecundity was reduced in groups fed CaBP for both parasites, however this was only significant for H. contortus (P < 0.001), in a dose dependent manner. In trial 2, four groups of six infected lambs each were used, which received the carob diets CaBP or CaBP + PEG, and the tannin-free diets with or without PEG (C or C + PEG). Results showed that FEC of Groups C, C + PEG, and CaBP + PEG were comparable throughout the trial, while the group receiving only CaBP showed lower FEC from DAY 25 onwards. AWC showed a reduction (67.7 %) only for H. contortus (P < 0.03). Reversal of the anthelmintic effect of CaBP after PEG administration suggested that CT contributed to the anthelmintic action. However, no effect of CaBP was observed on T. colubriformis AWC and on female worm fecundity for both species. Finally, for trial 3 four groups of six lambs each received a diet based on CaBP, sainfoin (S) or a combination (CaBP + S) and were compared to a control (C) diet of lucerne. On DAY 37 FEC values in groups CaBP + S and S tended to be lower compared to the two other groups (C, CaBP), while for AWCs no significant differences were observed for both parasites. The fecundity of H. contortus and T. colubriformis demonstrated significant differences between the treated and control groups, with lower values in the animals receiving CaBP + S. Overall, the results supported the hypothesis that carob had an anthelmintic effect due to its CT, but there was no clear indication of a synergistic effect with sainfoin.

Comparison of the effect of polyethylene glycol and simultaneous administration of polyethylene glycol with probiotics in the treatment of chronic functional constipation: a clinical trial

Background and aims: Constipation is one of the most common issues in pediatrics. The aim of this study was to compare the effect of polyethylene glycol and the simultaneous administration of polyethylene glycol along with probiotics in the treatment of chronic functional constipation. Materials and Methods: In this randomized double-blind clinical trial, 150 children with chronic functional constipation referred to Imam Ali Clinic affiliated with Shahrekord University of Medical Sciences from 2017 to 2018 were included. The first group (A) consumed 1 g/ kg of body weight per day of water-soluble polyethylene glycol powder and the second group (B) consumed a probiotic powder and 1 g/kg of body weight of the water-soluble polyethylene glycol powder daily. In weeks 0, 1, and 2, questionnaires were filled out by the parents of the children and the data were analyzed. Results: The results showed that there was no significant difference in any of the variables between groups A and B (P=0.07) including the frequency of fecal excretion in week 1 (77% and 71%) and week 2 (4% and 5.4%) and stool consistency in week 1 (4% and 6.7%) and week 2 (86.7% and 92%). Moreover, there was no significant difference between groups A and B in any of the variables frequency of painful excretion in week 1 (74% and 73%, respectively) and week 2 (5.3% and 4%, respectively), frequency of abdominal pain in week 1 (61.3% and 49.3%, respectively) and week 2 (4% and 5.3%, respectively), and the frequency of fecal incontinence in week 1 (22.77% and 18.7%, respectively) and week 2 (6.7% and 1.3%) (P&gt;0.05, respectively). Conclusion: Our results indicated that the administration of probiotic supplement (Lactobacillus Rhamnosus, Lactobacillus acidophilus, Lactobacillous Bulgaricus) has no effect on the improvement of symptoms in children with chronic constipation.

Factors Affecting Proximal Colon Cleansing Based on Bowel Movement Kinetics: A Prospective Observational Study.

Background Previous studies have suggested that relatively poor bowel preparation in the proximal colon, compared to that in the distal colon, could decrease the usefulness of colonoscopy. The aim of this study was to determine whether the “first defecation time” after polyethylene glycol (PEG) administration affects the cleansing quality in the proximal colon. Methods A total of 425 individuals who were scheduled to undergo a screening colonoscopy were enrolled prospectively at the healthcare center of St. Vincent's Hospital, Suwon, Korea, between April 2015 and March 2016. Bowel cleansing was performed using 4 L of PEG. Surveys were conducted to obtain information regarding the “first defecation time.” Endoscopists assessed the quality of bowel preparation in each bowel segment. Results We investigated 425 consecutive eligible cases. The mean “first defecation time” after PEG administration was 54.35 min. The quality of bowel preparation was poorer in the proximal colon than that in the distal colon. The adequate (excellent, good) and inadequate (fair, poor) proximal colon preparation groups comprised 360 (84.7%) and 65 (15.3%) patients, respectively. A multivariate analysis revealed that female gender (P = 0.029), small waist circumference (P = 0.027), and the long “first defecation time” (P = 0.034) were independently associated with inadequate bowel preparation in the proximal colon. Conclusion Our data document that the “first defecation time,” female gender, and a small waist circumference affect the quality of preparation in the proximal colon. Inadequate preparation in the proximal colon was more common in females. Patients with these factors undergoing colonoscopy should be monitored carefully.

Feed resource selection of Criollo goats is the result of an interaction between plant resources, condensed tannins and Haemonchus contortus infection

The tropical deciduous forest (TDF) is an ecosystem with a heterogeneous array of plant species containing different condensed tannin (CT) content. Recent studies explored the effect of polyethylene glycol (PEG) or Haemonchus contortus infection on the intake and feed resource selection of goats. These factors have not been investigated simultaneously. The present study evaluated the role of infection with the abomasal parasitic nematode Haemonchus contortus and the effect of neutralizing CT with PEG on the feed resource selection of Criollo goats in a cafeteria trial. A group of 22 Criollo goats (31.7 ± 4.8 kg) habituated to browse the TDF, were assigned to four groups: two groups were artificially infected with H. contortus (6000 L3per os) and received PEG (50 mg/day) (INF + PEG group) or no PEG (INF group) and the other two groups were kept free of infection with moxidectin (0.4 mg/kg BW sub-cutaneously) and received either PEG (MOX + PEG) or no PEG (MOX). Intake and resource selection of four shrub plant species (Havardia albicans, Gymnopodium floribundum, Leucaena leucocephala and Piscidia piscipula) by goats, and the dynamics of faecal H. contortus egg excretion were determined daily. Intake varied depending on the interaction between plant resource and the infection level (P < 0.001), and between plant resource and whether goats were dosed with PEG (P < 0.001). Excretion of H. contortus eggs was decreased by 69% and 72% for groups with and without PEG administration, respectively. Infected groups had a higher CT intake. The use of PEG reduced intake of L. leucocephala and increased the selection of H. albicans, a high-CT and high crude protein (CP) resource. Animals infected with H. contortus ingested more high-CT resources. Furthermore, CP intake was lower in PEG dosed goats, possibly to reduce the energetic cost associated with urinary nitrogen excretion. Selection of feed resources varied depending on parasite infection, PEG dosage and plant resource. We concluded that biological interactions influencing intake and selection of feed resources in goats are complex, rather than arising from a single factor such as parasite infection or secondary compounds such as CT. These findings support that goats’ resource selection is a complex process aimed at nutritional optimization.

Scientific and Regulatory Policy Committee Points to Consider: Histopathologic Evaluation in Safety Assessment Studies for PEGylated Pharmaceutical Products.

Colorless, intracytoplasmic vacuoles occur in multiple tissues in animals following repeated administration of polyethylene glycol (PEG)-conjugated molecules. The extent of vacuolation depends on physical characteristics and molecular backbone of the PEG and the dose, product, drug target/pharmacology, and duration of exposure. The collective experience gathered from multiple nonclinical toxicology studies of PEGylated biopharmaceuticals indicates that in general, PEG-related vacuolation is not associated with demonstrable cell and tissue damage or dysfunction and is reversible with sufficient duration of drug-free periods. Existing data are insufficient to predict whether nonclinical animal species differ in their sensitivity to develop PEG-associated vacuoles; however, recent data suggest that there may be species differences. Recent comprehensive reviews have addressed the basic challenges in developing PEGylated pharmaceutical products, including general reference to and description of PEG-associated tissue findings. These manuscripts have identified gaps in our current understanding of PEG-associated vacuolation, including the lack of a widely accepted standardized histological terminology and criteria to record and grade the severity of vacuolation as well as insufficient knowledge regarding the nature of the contents of these vacuoles. The goal of this article is to help address some of the gaps identified above by providing points to consider, including a pictorial review of PEG-associated microscopic findings, when evaluating and reporting the extent, severity, and significance (adversity or lack of adversity) of PEG-associated cytoplasmic vacuolation in safety assessment studies. [Box: see text].

HSV1/2 Genital Infection in Mice Cause Reversible Delayed Gastrointestinal Transit: A Model for Enteric Myopathy.

In an interesting investigation by Khoury-Hanold et al. (1), genital infection of mice with herpes simplex virus 1 (HSV1) were reported to cause multiple pelvic organ involvement and obstruction. A small subset of mice succumbed after the first week of HSV1 infection. The authors inferred that the mice died due to toxic megacolon. In a severe form of mechanical and/or functional obstruction involving gross dilation of the colon and profound toxemia, the presentation is called “toxic megacolon.” The representative observations by Khoury-Hanold likely do not resemble toxic megacolon. The colon was only slightly dilated and benign appearing. Importantly, HSV1 infection affected the postjunctional mechanisms of smooth muscle relaxation like the sildenafil-response proteins, which may have been responsible for defective nitrergic neurotransmission and the delayed transit. Orally administered polyethylene glycol reversed the gastrointestinal “obstruction,” suggesting a mild functional type of slowed luminal transit, resembling constipation, rather than toxic megacolon, which cannot be reversed by an osmotic laxative without perforating the gut. The authors suggest that the mice did not develop HSV1 encephalitis, the commonly known cause of mortality. The premature death of some of the mice could be related to the bladder outlet obstruction, whose backflow effects may alter renal function, electrolyte abnormalities and death. Muscle strip recordings of mechanical relaxation after electrical field stimulation of gastrointestinal, urinary bladder or cavernosal tissues shall help obtain objective quantitative evidence of whether HSV infection indeed cause pelvic multi-organ dysfunction and impairment of autonomic neurotransmission and postjunctional electromechanical relaxation mechanisms of these organs.