Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.

Vertically aligned montmorillonite aerogel-encapsulated polyethylene glycol with directional heat transfer paths for efficient solar thermal energy harvesting and storage

The conversion and storage of photothermal energy using phase change materials(PCMs)represent an optimal approach for harnessing clean and sustainable solar energy.Herein,we encapsulated polyethylene glycol(PEG)in montmorillonite aerogels(3D-Mt)through vacuum impregnation to prepare 3D-Mt/PEG composite PCMs.When used as a support matrix,3D-Mt can effectively prevent PEG leakage and act as a flame-retardant barrier to reduce the flammability of PEG.Simultaneously,3D-Mt/PEG demonstrates outstanding shape retention,increased thermal energy storage density,and commendable thermal and chemical stability.The phase transition enthalpy of 3D-Mt/PEG can reach 167.53 J/g and remains stable even after 50 heating-cooling cycles.Furthermore,the vertical sheet-like structure of 3D-Mt establishes directional heat transport channels,facilitating efficient phonon transfer.This configuration results in highly anisotropic thermal conductivities that ensure swift thermal responses and efficient heat conduction.This study addresses the shortcomings of PCMs,including the issues of leakage and inadequate flame retardancy.It achieves the development and design of 3D-Mt/PEG with ultrahigh strength,superior flame retardancy,and directional heat transfer.Therefore,this work offers a design strategy for the preparation of high-performance composite PCMs.The 3D-Mt/PEG with vertically aligned and well-ordered array structure developed in this research shows great potential for thermal management and photothermal conversion applications.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.

Hyponatremic encephalopathy due to polyethylene glycol-based bowel preparation for colonoscopy:A case report

BACKGROUND Adequate bowel preparation is critical for colonoscopy screening.At present,the most widely used intestinal cleaner recommended at home and abroad is Polyethylene glycol(PEG).Intestinal cleansers can cause electrolyte disturbances and hyponatremia.However,hyponatremic encephalopathy due to hyponatremia induced by PEG solution,although rare,can lead to serious irreversible sequelae and even death.CASE SUMMARY In this report,we discuss a case of neurological dysfunction due to hyponatremia,also known as hyponatremic encephalopathy,observed in a 63-year-old woman who underwent PEG-based bowel preparation for colonoscopy.She was eventually transferred to our intensive care unit for treatment due to her Glasgow Coma Scale score of 9/15(Eye opening 2;Verbal response 1;Motor response 6)and abnormal laboratory tests.CONCLUSION Physicians should be thoroughly familiarized with the patient’s history before prescribing PEG for bowel preparation,and timely identification of patients with hyponatremic encephalopathy is essential as delayed treatment is associated with poor neurological outcomes.An intravenous infusion of 3%sodium chloride is recommended at the onset of early symptoms.The goal of treatment is to adequately treat cerebral edema while avoiding serum sodium correction beyond 15 to 20 m Eq/L within 48 h of treatment to prevent osmotic demyelination syndrome.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo

Background: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol(PEG) crosslinked decellularized single liver lobe scaffolds(DLSs), and establish its suitability as a graft for long-term liver tissue engineering. Methods: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate(SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor(VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells(HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. Results: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young’s modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. Conclusions: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Anaphylactic shock induced by polyethylene glycol after bowel preparation for the colorectal cancer surgery:A case report

BACKGROUND Polyethylene glycol(PEG)is widely used as an additive because of its hydrophilic and chemically inert properties.However,there are been increasing reports of PEG allergies,including anaphylaxis,although they are still rare.This case report aims to raise awareness,that the commonly used bowel cleansing agent containing PEG can cause serious allergic reactions.CASE SUMMARY Prior to surgery for sigmoid colon cancer,a 63-year-old man was prescribed a bowel cleansing agent containing PEG.Within 30 min of ingestion,he developed symptoms of anaphylactic shock and did not respond to initial intramuscular epinephrine injection.Under diagnosis of anaphylaxis to PEG,he was stabilized with fluid hydration and continuous norepinephrine infusion.CONCLUSION While allergic reactions to PEG are rare,they can be life-threatening.Therefore,it is crucial for clinicians to be aware of this possibility and to diagnose and resuscitate patients immediately.

Polyethylene glycol (PEG) as a benign solvent for Knoevenagel condensation

The Knoevenagel condensation of aromatic aldehydes with active methylene compound proceeded efficiently in polyethylene glycol at room temperature with L-proline as catalyst. The yield is high and the products had E-isomer dominantly. Polyethylene glycol containing L-proline could be recycled and reused for several times without noticeably decreasing in productivity.

Effect of Free Cells and Additional Supporting Material on Performance of Polyethylene Glycol (PEG)-Pellet Reactor to Treat NH4-N Contaminated Groundwater

To study the effect of free cells (suspended bacteria) on performance of entrapped bacteria system (i.e. polyethylene glycol (PEG)-pellet reactor) to treat NH4-N contaminated groundwater, two PEG-pellet reactors with a lot of free cells - Reactor A containing PEG-pellet and Reactor B containing PEG-pellet and supporting material - and the another control reactor without free cells (Reactor C) were set-up. Three reactors were operated under various NH4-N concentrations (40-60 mg/L) and various temperatures (5-25oC). The results show that the free cells effected on the NH4-N removal efficiency significantly. The free cells developed to be a biofilm layer on the pellet surface for Reactor A, the biofilm layer caused the decreasing NH4-N diffusion and incomplete nitrification eventually. On the other hand, most free cells attached to the supporting material for Reactor B. Although the NH4-N could diffuse properly, the free cells consuming acetate caused the added acetate was insufficient for complete denitrification. However, the results suggest that the supporting material could reduce the effect of free cells on the reactor performance at low temperature as indicated by 1) higher efficiency and 2) lower activation energy (Ea) for nitrification and denitrification in Reactor B than Reactor A.

Effect of Silicon (Si) Application on Phoenix dactylifera L. Growth under Drought Stress Induced by Polyethylene Glycol (PEG) in Vitro

This study was carried out to investigate the effects of silicon (Si) 3.6 mM (as calcium silicate) under drought stress induced by polyethylene glycol “PEG” at 15% (MW 8000), in addition to the control treatment on growth and some biochemical constituents of date palm cv. Barhee cultured in vitro. Drought stress (15% PEG) depressed the growth of shoot and decreased protein content and chlorophyll concentration. Addition of 3.6 mM Si could improve the growth of shoot and increase the protein content and leaf chlorophyll concentrations of stressed plants. The inclusion of Si to the PEG containing medium significantly increased the catalase (CAT) and superoxide dismutase (SOD) activity in regenerated shoot, compared to other treatments. As well as drought stress 15% PEG induced significant accumulation of shoots proline, which were decreased by added silicon. Moreover, the results were also supported by the observation that PEG stress-induced decrease the response percentage of root induction and root lengths was reversed by added silicon. Addition of Si obviously significantly increased the wax content in leaves, response percentage of root induction and root lengths of plantlets under drought stress. The results of this study indicate that the application of silicon improved growth attributes, effectively mitigate the adverse effect of drought, and increase tolerance of date palm plants for drought stress during the course of date palm tissue cultures.

Synthesis and Characterization of Storage Energy Materials Prepared from Nano-crystalline Cellulose/Polyethylene Glycol

This paper gives a brief report of the synthesis of a new kind of solid-solid phase change materials （SSPCMs）, nano-crystalline cellulose/polyethylene glycol （NCC/PEG）. These PCMs have very high ability for energy storage, and their enthalpies reach 103.8 J/g. They are composed of two parts, PEG as functional branches for energy storage, and NCC as skeleton. The flexible polymer PEG was grafted onto the surface of rigid powder of NCC by covalent bonds. The results of DSC, FT-IR were briefly introduced, and some comments were also given.

Isothermal Crystallization Kinetics of Microencapsulated Polyethylene Glycol Particles

The microenapsulated polyethylene glycol （PEG） with different molecular weight by a fluidized coating method has been prepared and the crystallization behaviors of PEG particles in three-dimensional confined vohume were investigated by using differential scanning calorimetry （DSC） measurement. The results showed that the width of the crystallization peak of PEG increases and its height gradually diminishes in case that the PEG particles are microencapsulated. Compared with the non-microencapsulated PEG particles, the proportion of the first crystallization peak of microencapsulated PEG particle increases, and that of the second one decreases. The reason for the difference maybe is that the crystallization process of microencapsulated PEG particles is uniform and the crystallization ends when the spherulites touch the wall, thus the opportunity of producing the second crystallization peak was relatively reduced.

Effects of NaCl and Iso-Osmotic Polyethylene Glycol Stress on Na^+/H^+Antiport Activity of Three Malus species with Different Salt Tolerance

Salt stress contains osmotic and ionic stress, while iso-osmotic polyethylene glycol （PEG） has only osmotic stress. This study aimed to compare the different effects on the activity of H＋-ATPase, proton pump and Na＋/H＋antiport in Malus seedlings between osmotic and ionic stress. Species of salt tolerant Malus zumi, middle salt tolerant Malus xiaojinensis and salt sensitive Malus baccata were used as experimental materials. Malus seedlings were treated with NaCl and iso-osmotic PEG stress. The activity of H＋-ATPase, proton pump and Na＋/H＋antiport of plasmolemma and tonoplast in Malus seedlings were obviously increased under salt stress, and those in salt-tolerant species increased more. Under the same NaCl concentration, the activity of H＋-ATPase, proton pump and Na＋/H＋antiport of plasmolemma and tonoplast in salt-tolerant species were all obviously higher than those in salt-sensitive one. Higher Na＋/H＋antiport activity of plasmolemma and tonoplast in salt-tolerant species could help to extrude and compartmentalize sodium in roots under salt stress. The ascent rate of activity of H＋-ATPase, proton pump and Na＋/H＋antiport in Malus seedlings under the three salt concentration stress was all obviously higher than that under the iso-osmotic PEG stress. It indicated that the sodium ion effect had more stimulation on the activity of H＋-ATPase, proton pump and Na＋/H＋antiport in salt-tolerant species, and salt-tolerant species has higher capability of sodium extrusion and compartmentalization in roots and is therefore more salt tolerant.

利用PEG/Na_(2)CO_(3)双水相乳液法制备碳酸钙微球及其形成机理

具有微隔室化作用的乳液法是制备球形材料的有效手段。本研究利用聚乙二醇(PEG)与碳酸钠(Na_(2)CO_(3))组成的双水相体系制备碳酸钙微球。首先对双水相的形成条件进行了探究,并绘制相图。然后以Ca Cl_(2)为钙源、PEG/Na_(2)CO_(3)双水相乳液的分散相Na_(2)CO_(3)为碳源,制备了高分散性的Ca CO_(3)微球。研究了双水相体系组成、复分解反应条件等因素对Ca CO_(3)成球效果的影响,分析了产物的微观形貌、晶体结构和粒径分布。结果表明,在33%PEG8000-7%Na_(2)CO_(3)(质量分数)的双水相乳液中,Ca Cl_(2)溶液与PEG/Na_(2)CO_(3)乳液体积比为1∶15、反应时间为1min、陈化时间为0.5h的最优条件下,合成了球形度高、粒径为3.4μm的Ca CO_(3)微球,且Ca CO_(3)以球霰石为主(高达95.72%),包含少量方解石;其成球机理为,Ca^(2+)渗透至微小球形液滴的内部,在具有微隔室化的细小空腔中与CO_(3)^(2-)发生反应,形成晶核并快速生成球霰石,PEG-水环境阻止球霰石发生溶解-重结晶,抑制了球霰石向方解石发展的趋势,然后晶核在双水相体系的大分子拥挤微环境下限域生长,最终得到球形结构。

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy

AIM:To compare the bowel cleansing efficacy,tolerability and acceptability of split 2-L polyethylene glycol(PEG)-citrate-simethicone(PEG-CS)plus bisacodyl(BIS)vs 4-L PEG for fecal occult blood test-positive screening colonoscopy.METHODS:This was a randomised,observer-blind comparative study.Two hundred and sixty-four subjects underwent screening colonoscopy(mean age 62.5±7.4years,male 61.7%).The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations.Interventions:BIS plus PEG-CS:3 tablets of 5-mg BIS at 16:00,PEG-CS 1-L at 19:00 and 1-L at7:00,4-L PEG:3-L at 17:00,and 1-L at 7:00.Colonoscopy was carried out after 11:00,at least 3 h after the completion of bowel preparation.Bowel cleansing was evaluated using the Harefield Cleansing Scale.RESULTS:Bowel preparation was successful for 92.8%of subjects in the PEG-CS group and for 92.1%of subjects in the 4-L PEG(RR=1.01;95%CI:0.94-1.08).BIS+PEG-CS was better tolerated than 4-L PEG.A greater rate of patients in the BIS+PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group.Subjects in the BIS+PEG-CS group rated the prep as good or satisfactory in 90.6%as compared to 77%in the 4-L PEG(P=0.003).Subjects receiving BIS+PEGCS stated they fully adhered to instructions drinking all the 2-L solution in 97.1%compared with 87.3%in the4-L PEG(P=0.003).CONCLUSION:BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split4-L PEG for screening colonoscopy.This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy.

Randomized controlled trial of sodium phosphate tablets vs polyethylene glycol solution for colonoscopy bowel cleansing

AIM: To compare efficacy, patient compliance, acceptability, satisfaction, safety, and adenoma detection rate of sodium phosphate tablets (NaP, CLICOLONTM) to a standard 4 L polyethylene glycol (PEG) solution for bowel cleansing for adults undergoing colonoscopy.

Lubiprostone used with polyethylene glycol in diabetic patients enhances colonoscopy preparation quality

AIM: To assess the additive effect of lubiprostone on the quality of colon preparation in diabetics given single-dosed polyethylene glycol electrolyte(PEG)for colonoscopy.METHODS:This was an investigator-initiated,singlecenter,single-blinded prospective trial comparing the efficacy of L+PEG to PEG alone on colon preparation quality in diabetics undergoing screening colonoscopy.The study was approved by our institution’s IRB.The PEG was given as a single-dose to address patientcompliance concerns voiced by our IRB with splitdosing.All patients received only clear liquids the day prior to colonoscopy.Experimental group(Grp L)received PEG+1 dose L 2 h prior to and 2 h after PEG completion.Control group(Grp C)received only PEG the evening prior to the colonoscopy.Patients were randomly assigned to one of the 2 groups.The endoscopist was blinded to which colon prep was given and all colonoscopies were complete.Upon colonoscopy completion,the endoscopist rated the colon prep-quality by a validated 5-point Likert scale(1-excellent to 5-inadequate).RESULTS:Sixty patients were enrolled in the study;30 Grp L and 30 Grp C.Overall,patients were excluded due to study non-completion in 12(41%)Grp L and 5(17%) Grp C,P=0.04.Average colon preparation score Grp L =2.47 and Grp C=3.00,P=0.09.Although this was not statistically significant,there was a trend towards improved colon prep in Grp L.Statistical significance may have been achieved if completion rates had been similar between both study groups.CONCLUSION:Use of 2-L capsules with PEG resulted in a trend towards improved colon prep over PEG alone in diabetic patients when given as a single-dose regimen.

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries

Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce： （1） Immediate loss of axonal continuity, sensory signaling, and motor control; （2） Wallerian rapid （1-3 days） degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months （if ever, after ablations） by slowly-regenerating （1 mm/d）, proximal-stump outgrowths that must specifically reinnervate denervated targets; （3） Poor acceptance of microsutured nerve allografts, even if tissue-matched and immune-suppressed. Repair of transections/ablations by neurorrhaphy and well-specified-sequences of PEG-fusion solutions （one containing polyethylene glycol, PEG） successfully address these problems. However, conundrums and confusions regarding unorthodox and dramatic results of PEG-fusion repair in animal model systems often lead to misunderstandings. For example, （1） Axonal continuity and signaling is re-established within minutes by non-specifically PEG-fusing （connecting） severed motor and sensory axons across each lesion site, but remarkable behavioral recovery to near-unoperated levels takes several weeks; （2） Many distal stumps of inappropriately-reconnected, PEG-fused axons do not ever （Wallerian） degenerate and continuously innervate muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; （3） Host rats do not reject PEG-fused donor nerve allografts in a non-immuno-privileged environment with no tissue matching or immunosuppression; （4） PEG fuses apposed open axonal ends or seals each shut （thereby preventing PEG-fusion）, depending on the experimental protocol; （5） PEG-fusion protocols produce similar results in animal model systems and early human case studies. Hence, iconoclastic PEG-fusion data appropriately understood might provoke a re-thinking of some Neuroscience dogma and a paradigm shift in clinical treatment of peripheral nerve injuries.

Effect of exogenous spastin combined with polyethylene glycol on sciatic nerve injury

Polyethylene glycol can connect the distal and proximal ends of an injured nerve at the cellular level through axonal fusion to avoid Wallerian degeneration of the injured distal nerve and promote peripheral nerve regeneration.However,this method can only prevent Wallerian degeneration in 10% of axons because the cytoskeleton is not repaired in a timely fashion.Reconstruction of the cytoskeletal trunk and microtubule network has been suggested to be the key for improving the efficiency of axonal fusion.As a microtubule-severing protein,spastin has been used to enhance cytoskeletal reconstruction.Therefore,we hypothesized that spastin combined with polyethylene glycol can more effectively promote peripheral nerve regeneration.A total of 120 male Sprague-Dawley rats were randomly divided into sham,suture,polyethylene glycol,and polyethylene glycol + spastin groups.In suture group rats,only traditional nerve anastomosis of the end-to-end suture was performed after transection of the sciatic nerve.In polyethylene glycol and polyethylene glycol + spastin groups,50 μL of polyethylene glycol or 25 μL of polyethylene glycol + 25 μL of spastin,respectively,were injected immediately under the epineurium of the distal suture.Sensory fiber regeneration distance,which was used to assess early nerve regeneration at 1 week after surgery,was shortest in the suture group,followed by polyethylene glycol group and greatest in the polyethylene glycol + spastin group.Behavioral assessment of motor function recovery in rats showed that limb function was restored in polyethylene glycol and polyethylene glycol + spastin groups at 8 weeks after surgery.At 1,2,4 and 8 weeks after surgery,sciatic functional index values and percentages of gastrocnemius muscle wet weight were highest in the sham group,followed by polyethylene glycol + spastin and polyethylene glycol groups,and lowest in the suture group.Masson staining was utilized to assess the morphology of muscle tissue.Morphological changes in skeletal muscle were detectable in suture,polyethylene glycol,and polyethylene glycol + spastin groups at 1,2,4,and 8 weeks after surgery.Among them,muscular atrophy of the suture group was most serious,followed by polyethylene glycol and polyethylene glycol + spastin groups.Ultrastructure of distal sciatic nerve tissue,as detected by transmission electron microscopy,showed a pattern of initial destruction,subsequent disintegration,and gradual repair in suture,polyethylene glycol,and polyethylene glycol + spastin groups at 1,2,4,and8 weeks after surgery.As time proceeded,axonal ultrastructure gradually recovered.Indeed,the polyethylene glycol + spastin group was similar to the sham group at 8 weeks after surgery.Our findings indicate that the combination of polyethylene glycol and spastin can promote peripheral nerve regeneration.Moreover,the effect of this combination was better than that of polyethylene glycol alone,and both were superior to the traditional neurorrhaphy.This study was approved by the Animal Ethics Committee of the Second Military Medical University,China(approval No.CZ20170216) on March 16,2017.

Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer

AIM To study tumor response, and tolerability of arterially directed embolic therapy(ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases(CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients.METHODS Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status(PS), tumor marker antigens, and quality of life(QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale(PPS).RESULTS We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response(CR), 48% of partial response(PR), 8% stable disease(SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease(PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo(range 0.8-6). Median follow-up was 14 mo(0.8-25 range). ADETs were performed with no complications. Observed side effects(mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.