Saline Group Research Articles

Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat model

IntroductionVital pulp therapy (VPT) is performed to preserve dental pulp. However, the biocompatibility of the existing materials is of concern. Therefore, novel materials that can induce pulp healing without adverse effects need to be developed. Resolvin D2 (RvD2), one of specialized pro-resolving mediators, can resolve inflammation and promote the healing of periapical lesions. Therefore, RvD2 may be suitable for use in VPT. In the present study, we evaluated the efficacy of RvD2 against VPT using in vivo and in vitro models. MethodsFirst molars of eight-week-old male Sprague–Dawley rats were used for pulpotomy. They were then divided into three treatment groups: RvD2, phosphate-buffered saline, and calcium hydroxide groups. Treatment results were assessed using radiological, histological, and immunohistochemical (GPR18, TNF-α, Ki67, VEGF, TGF-β, CD44, CD90, and TRPA1) analyses. Dental pulp-derived cells were treated with RvD2 in vitro and analyzed using cell-proliferation and cell-migration assays, real-time PCR (Gpr18, Tnf-α, Il-1β, Tgf-β, Vegf, Nanog, and Trpa1), ELISA (VEGF and TGF-β), immunocytochemistry (TRPA1), and flow cytometry (dental pulp stem cells: DPSCs). ResultsThe formation of calcified tissue in the pulp was observed in the RvD2 and calcium hydroxide groups. RvD2 inhibited inflammation in dental pulp cells. RvD2 promoted cell proliferation and migration and the expression of TGF-β and VEGF in vitro and in vivo. RvD2 increased the number of DPSCs. In addition, RvD2 suppressed TRPA1 expression as a pain receptor. ConclusionRvD2 induced the formation of reparative dentin, anti-inflammatory effects, and decreased pain, along with the proliferation of DPSCs via the expression of VEGF and TGF-β, on the pulp surface in pulpotomy models.

Effectiveness of Hypertonic Saline, Polidocanol, and Glycerol as Sclerosing Agent: An Experimental Study in Javan Rabbits (Lepus nigricollis)

INTRODUCTION: Therapeutic approaches to varicose veins include sclerotherapy, laser ablation, and surgery. Using sclerosing agents such as hypertonic saline, polidocanol, and glycerol can be an option in cases of recurrent varicose veins. This study aimed to assess the effectiveness of hypertonic saline, polidocanol, and glycerol as sclerosant agents in an in vivo study. MATERIAL AND METHODS: This was an experimental study on 24 Javan rabbits, divided into three treatment groups: hypertonic saline (group I, n=8), polidocanol (group II, n=8), and glycerol (group III, n=8). All animals received treatment by injection into the vein behind the ear, then vein damming 10 minutes later. Punch tissue samples for standard histopathological examination were taken from blood vessels at 1 hour, 24 hours, 7 days, and 45 days post-treatment across all groups. The histopathology changes were scored based on inflammation, proliferation, luminal narrowing, and fibrosis. RESULT: No differences were observed in the degrees of inflammation, proliferation, luminal narrowing, or fibrosis at different observation intervals. However, a significant and positive correlation was found between inflammation, vascular proliferation, and fibrosis with all sclerosing agents (p<0.005). No significant correlation exists in the scoring of luminal narrowing among any sclerosing agent (p>0.005). CONCLUSION: Hypertonic saline, polidocanol, and glycerol demonstrated comparable efficacy as sclerosing agents in vivo concerning fibrosis, vascular proliferation, and inflammation.

Determining Efficacy of Intracanal Cryotherapy on Post Endodontic Pain in Irreversible Pulpitis

Endodontic cryotherapy is a procedure that reduces pain and inflammation by applying cold to tissues, aiming to decrease post-endodontic pain. Objectives: To compare the effectiveness of cryo-treated endodontic irrigant in reducing post-endodontic pain in mandibular molars with irreversible pulpitis. Methods: This comparative analytical study was conducted from December 2023 to February 2024 in the Department of Operative Dentistry at Lahore Medical and Dental College. It included patients of both genders, aged 18 to 60, with symptomatic irreversible pulpitis in mandibular molars and pre-endodontic pain of VAS 7-10 for 10 days or less. Patients were divided into two groups: Group A (normal saline) and Group B (cryotherapy). Patients were instructed on using the Visual Analogue Scale (VAS) to assess pain. Group B received final irrigation with 20 ml normal saline at 2.5°C for 5 minutes, while Group A received 20 ml normal saline at room temperature. Pain scores were recorded preoperatively and at 24 and 48 hours’ post-treatment via telephone interviews. Data were analyzed using SPSS version 25 and a repeated measures ANOVA test assessed VAS scores across time points. A p-value <0.05 was considered significant. Results: 45 (46%) were male and 53 (54%) were female patients, with mean age of patients being 35.71 ± 10.71years. At 24 hours postoperatively, the mean VAS score was 1.51 ± 1.2 for the normal saline group and 0.98 ± 0.9 for the cryo-treated saline group. By 48 hours postoperatively, the mean VAS score further decreased to 0.27 ± 0.5 for the normal saline group and 0.12 ± 0.4 for the cryo-treated saline group. The mean differences in VAS scores at 24 hours showed significant difference in mean pain score (P-value<0.05) but at 48 hours between the two groups showed no significant difference (p = 0.104). Conclusions: Both saline groups significantly decreased pain, the type of saline, normal or cryo-treated, did not significantly impact overall pain scores differently between the groups.

Peritoneal lavage with sterile water reduces IL-1 levels and postoperative adhesions following laparotomy in rats

Peritoneal lavage with normal saline is common in abdominal surgeries, yet recent studies indicate that it increases intraperitoneal adhesion risks. This study compares the effects of peritoneal lavage with normal versus sterile water on interleukin-1 (IL-1) levels and intraperitoneal adhesion following laparotomy in rats. In this post-test control group study, 20 adult Wistar rats were subjected to laparotomy before being randomly divided into two groups to receive either intraperitoneal lavage with normal saline (0.9% NaCl ) or sterile water. After 7 days, IL-1 level and degree of adhesion were evaluated. The saline group had higher adhesion levels (4 rats with grade 4, 5 with grade 3, 1 with grade 2) than the sterile water group, which had lower levels (2 rats with grade 3, 5 with grade 2, 3 with grade 1). There was a significant difference in IL-1 levels between the sterile water group (37,111.6 ± 6,535.61 pg/ml) and the normal saline group (57,456.3 ± 10,583.41 pg/ml). There was a significant correlation between IL-1 levels and adhesion grade (p=0.008). Intraperitoneal lavage with sterile water results in significantly lower adhesion grade and IL-1 levels than normal saline, suggesting its potential for reducing postoperative adhesions. Further studies are needed to elucidate the mechanism of reduced adhesion and inflammation associated with sterile water lavage.

Evaluation of Reproductive Histology Response of Adult Fasciola hepatica in Goats Vaccinated with Cathepsin L Phage-Exposed Mimotopes.

Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis' gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output.

Pharmacokinetic/Pharmacodynamic modelling of Saxagliptin and its active metabolite, 5-hydroxy Saxagliptin in rats with Type 2 Diabetes Mellitus

Background and purposesIt is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect.MethodsFirst, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX.ResultsA two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal Emax model and sigmoidal Emax with E0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration (Tmax=0.11 h, t1/2, ka=0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC50, EC50, 5−OH SAX=0.46EC50, SAX(parent), it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature.ConclusionsThe PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15units/kg/h for infants with CRT and 2 to 3units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

Autophagy regulates bone loss via the RANKL/RANK/OPG axis in an experimental rat apical periodontitis model.

Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05). Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05). Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.

Efficacy and Safety of Xylitol Nasal Irrigation after Functional Endoscopic Sinus Surgery: A Randomized Controlled Study

Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body’s own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.

DIPG-61. ARGININE DEPRIVATION USING ADI-PEG20 IMPROVES SURVIVAL IN A SYNGENEIC DIFFUSE MIDLINE GLIOMA MOUSE MODEL

Abstract BACKGROUND Diffuse midline glioma (DMG-H3K27) presents a significant challenge in paediatric oncology, with a &amp;lt;10% two-year survival rate despite standard palliative radiotherapy. Tumour infiltration behind the blood-brain barrier hampers drug delivery, contributing to clinical trial failures. ADI-PEG20 exploits tumour metabolic vulnerabilities: lack of argininosuccinate synthetase and reliability on extracellular arginine for proliferation. This study investigates ADI-PEG20’s efficacy in a syngeneic DMG mouse model. METHODS Twenty C57BL/6J mice were intracranially injected with a DMG cell line (H1H3BK27M, DNp53, PDGFRAD642V, Acvr1G328V) and monitored via bioluminescence imaging from day 7. Weekly treatments began on day 10, comprising ADI-PEG20 (5 I.U.) alone, ADI-PEG20 with concurrent radiation (2 Gy), radiation alone, or saline (0.9%), with each group comprising n=5. Radiation was administered 24 hours post-drug treatment. Bioluminescence imaging was conducted twice weekly, with mice culled upon symptom onset. Immunohistochemistry was performed on brain tissue. RESULTS The combination and ADI-PEG20 monotherapy cohorts exhibited comparable median survival rates, both surpassing those of the radiation-only and saline groups, with the latter exhibiting the lowest median survival. A significant disparity in survival curves was observed overall (p&amp;lt;0.0001), confirmed by log-rank (Mantel-Cox) test. Pairwise comparisons revealed significant differences in survival curves between the combination and radiation-only (p=0.0066), ADI-PEG20 monotherapy and radiation-only (p=0.0018), and ADI-PEG20 monotherapy and saline (p=0.0062) groups. Minimal divergence in IVIS signal intensity was noted across groups. Histological examination via H&amp;E staining demonstrated marked tumour regression in mice treated with ADI-PEG20 ± radiation, contrasting with the persistent tumour mass evident in the radiation-only and saline cohorts, alongside discernible heterogeneity in cellular phenotypes within the ADI-PEG20 ± groups. CONCLUSIONS In conclusion, ADI-PEG20 shows promise as a therapeutic strategy for DMG, offering a significant survival advantage over radiation and saline. Ongoing efforts will elucidate its mechanistic underpinnings, explore its efficacy across diverse DMG models, and assess synergistic interactions with immune-based therapies.

Assessing the efficacy of various irrigation solutions in dissolving organic tissue

For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the organic tissue dissolving activity of various irrigation solutions on bovine tooth pulp tissue. 40 extracted bovine mandibular anterior teeth (n = 10) were used for the study. Bovine pulp pieces (25 ± 5 mg) were placed in 1.5 ml Eppendorf tubes. Each tooth pulp sample was then covered with 1.5 ml of different irrigation solutions, dividing them into four groups: Group 1 with freshly prepared 5% Boric acid, Group 2 with 5% NaOCl, Group 3 with Irritrol, and Group 4 with Saline. Samples were left at room temperature for 30 min, then dried and reweighed. The efficacy of tissue dissolution ranked from highest to lowest was found to be NaOCl, Boric Acid, Irritrol, and saline (p < 0.05). It was observed that the decrease in the NaOCl group was greater than the decrease in the Irritrol and saline groups, and the decrease in the Boric acid group was significantly greater than the decrease in the saline group (p < 0.05). It also emphasizes the need for future studies to further investigate the effects of Irritrol and Boric Acid on tissue dissolution.

Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.

Intravenous magnesium sulfate improves orotracheal intubation conditions: A randomized clinical trial

BackgroundMuscle relaxation facilitates orotracheal intubation, but in some situations, neuromuscular blocking agents may be contraindicated. AimTo study the effect of intravenous magnesium sulfate perfusion before induction on orotracheal intubation conditions and the pressor response upon intubation. MethodsThis prospective, randomized, double-blind trial compared magnesium sulfate with saline solution as a placebo. The patients were randomized into two groups: the magnesium group (Group Mg+), which received 50 mg/kg of magnesium sulfate in 100 ml of saline 15 min before induction of anesthesia, and the saline group (Group Mg-), which received only 100 ml of saline 15 min before induction of anesthesia without magnesium sulfate. The induction in both groups was performed without neuromuscular blocking agents.Intubation conditions in both groups were compared using the Copenhagen consensus conference: ease of laryngoscopy, vocal cord position and/or movement, and response to intubation or cuff (cough or diaphragmatic movement). Intubation conditions were considered acceptable (excellent or good) or unacceptable (poor). Systolic, diastolic arterial pressures and heart rate were also recorded during the study. ResultsIn total, 76 patients (38 in each group) were included in this study. Clinically acceptable intubation conditions were significantly more observed in the magnesium group Mg + compared to the saline group Mg-: 36 patients (95 %) vs. 15 patients (39 %) (P < 0.001).Hemodynamic stability was more observed in the magnesium group, with a statistically significant lower heart rate throughout Mg + compared to the saline group. ConclusionAdministration of magnesium sulfate before induction of anesthesia significantly improved intubation conditions without the need for neuromuscular blocking agents.

Effect of Lignocaine on Postoperative Serum Lactate Dehydrogenase and Lactate Levels in Patients Undergoing Bowel Surgery

Objective: To evaluate effect of intraoperative lignocaine on postoperative serum LDH and lactate levels and to compare with placebo in patients undergoing bowel surgery. Methodology: This randomized controlled trial was conducted at the Department of Biochemistry, Islam Medical, Sialkot, Pakistan from August 2023 to January 2024. Serum LDH and lactate levels were measured preoperatively on automatic biochemical analyzer (produced by Beckman Coulter, GRM, 2166) was used to analyze, before extubation, and at 6 and 24 hours postoperatively, between patients who received intraoperative lignocaine versus those who received saline during bowel surgery under general anesthesia. Results: The study involved two groups: Group lignocaine (n = 20) where patients received 2% lignocaine at the rate of 1.5 mg/kg intravenous followed by maintenance infusion at the same rate until the end of surgery, and Group normal saline (n = 20) where patients received normal saline at the rate 1.5 mg/kg IV followed by infusion at the same rate until the end of surgery The average serum lactate postoperative, before extubation, 6 hours and 24 hours of lignocaine group was 2.68±0.32 mmol/l, 1.26±0.22 mmol/l, 1.09±0.28 mmol/l, and 1.15±0.13 mmol/l, respectively (p&lt;0.001). Whereas the average serum lactates at postoperative, before extubation, 6 hours and 24 hours of normal saline group was 2.86±0.37 mmol/l, 2.64±0.65 mmol/l, 2.15±0.31 mmol/l, and 1.65±0.38 mmol/l, respectively (p&lt;0.001). Conclusion: Patients undergoing bowel surgery who received intraoperative IV lignocaine exhibited lower postoperative serum LDH and lactate levels compared to those who received normal saline. It was also concluded that indirectly intravenous lignocaine also improves postoperative outcomes by reducing pain and hospital stay.

Ultrasound guided platelet rich plasma injections for post-traumatic greater occipital neuralgia following concussion: a pilot randomized controlled trial.

Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can be transient, frequently lasting only 1 month. As a potential alternative, platelet-rich plasma (PRP) injections are an emerging biological treatment with beneficial effects in peripheral nerve disorders. We investigated the feasibility, safety, and effectiveness of a single PRP injection for post-traumatic GON in comparison to saline or steroid/anesthetic injection. In this pilot randomized, double-blinded, placebo-controlled trial, 32 adults with post-traumatic GON were allocated 1:1:1 to receive a single ultrasound-guided injection of (1) autologous PRP (2) steroid/anesthetic or (3) normal saline. Our primary outcome was feasibility (recruitment, attendance, retention) and safety (adverse events). Exploratory measures included headache intensity and frequency (daily headache diaries) and additional questionnaires (headache impact, and quality of life) assessed at pre-injection, 1 week, 1 month, and 3 months post-injection. We screened 67 individuals, 55% were eligible and 95% of those participated. Over 80% of daily headache diaries were completed with 91% of participants completing the 3-month outcome questionnaires. No serious adverse events were reported. There were no significant differences between groups for headache intensity or frequency. Headache impact on function test-6 scores improved at 3 month in the PRP (β = -9.7, 95% CI [-15.6, -3.74], p = 0.002) and saline (β = -6.7 [-12.7, -0.57], p = 0.033) groups but not steroid/anesthetic group (p = 0.135). PRP is a feasible and safe method for treating post-traumatic GON with comparable results to saline and steroid/anaesthetic. Further trials with larger sample sizes are required.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT04051203.

Effects of Balanced Versus Saline-based Solutions on Acute Kidney Injury in Off-pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial

To determine whether balanced solutions can reduce the incidence of acute kidney injury after off-pump coronary artery bypass surgery compared with saline. Randomized controlled trial. Single tertiary care center. Patients who underwent off-pump coronary artery bypass surgery between June 2014 and July 2020. Balanced solution-based chloride-restrictive intravenous fluid strategy. The primary outcome was acute kidney injury within 7 postoperative days, as defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of acute kidney injury was 4.4% (8/180) in the balanced group and 7.3% (13/178) in the saline group. The difference was not statistically significant (risk difference, -2.86%; 95% confidence interval [CI], -7.72% to 2.01%; risk ratio, 0.61, 95% CI, 0.26 to 1.43; p = 0.35). Compared with the balanced group, the saline group had higher levels of intraoperative serum chloride and lower base excess, which resulted in a lower pH. In patients undergoing off-pump bypass surgery with a normal estimated glomerular filtration rate, the intraoperative balanced solution-based chloride-restrictive intravenous fluid administration strategy did not decrease the rate of postoperative acute kidney injury compared with the saline-based chloride-liberal intravenous fluid administration strategy.

Intravenous application of human umbilical cord mesenchymal stem cells alleviate neuropathic pain by suppressing microglia activation in rats

ObjectiveNeuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia. Methods30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM). ResultsCompared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group. ConclusionsOverall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.

A rapid strategy to develop personalized cancer nanovaccines for different immunogenic tumors.

e14670 Background: Therapeutic cancer vaccines aim to train the immune system and elicit antitumor immune responses, which are expected to fill the unmet medical need of immune checkpoint inhibitors. Despite tremendous efforts over the past decades, it remains challenging to prepare personalized cancer vaccines using a facile and rapid approach due to tumor diversity. CpG-ODN is a promising immunoadjuvant in cancer immunotherapy, and many clinical trials have been performed or are ongoing. However, commonly used phosphorothioate-modified CpG ODN easily induces protein aggregation and its long-term side effects are concerned. Here, we designed hollow large-pore mesoporous organosilica with sulfide bond to simultaneously load unmodified CpG-ODN with guanine-quadruplex (G4) structures and different tumor antigens to prepare personalized cancer vaccines in a simple, fast, and effective way. Methods: High-immunogenicE.G7-OVA lymphoma or low-immunogenic Lewis lung carcinoma (LLC) cells were subcutaneously inoculated into the left flanks to establish tumor-bearing mice. On days 4, 7, and 10 post tumor inoculation, cancer vaccines prepared using model antigen (OVA) or autologous tumor antigen (LLC tumor cell lysate) were subcutaneously injected into the right flanks of mice, respectively. Saline group, free tumor antigen group, free tumor antigen + CpG-ODN group, tumor antigen + organosilica group were used as controls. The size of tumors was monitored. Results: Cancer vaccines against E.G7-OVA showed high loading efficiencies of &gt;95% for both CpG-ODN and OVA, triggered antitumor immune response with high percentages of CD4+, CD8+, tetramer+CD8+ T cells in splenocytes, and effectively inhibited the growth of established tumor, compared with free OVA, free OVA + CpG-ODN, free OVA + organosilica groups. Cancer vaccines against LLC exhibited high loading efficiencies of &gt;95% and &gt;80% for CpG-ODN and LLC tumor cell lysate, activated antitumor immune response with high percentages of CD4+ and CD8+ T cells in splenocytes and CD8+ T, NK and M1 cells in tumor sites, and effectively inhibited the growth of established tumor, compared with control groups. Conclusions: Codelivery of CpG-ODN and different tumor antigens using hollow large-pore mesoporous organosilica elicits antitumor immunity against both high-immunogenic and low-immunogenic tumors.

Synergistic effect of ex-vivo quality and quantity cultured mononuclear cells and mesenchymal stem cell therapy in ischemic hind limb model mice

IntroductionChronic limb-threatening ischemia (CLTI) is a condition characterized by peripheral arterial disease and tissue damage caused by reduced blood flow. New therapies using various cell types, such as mesenchymal stem cells (MSCs) and mononuclear cells (MNCs), have been developed for the patients unresponsive to conventional therapies. MSCs are promising because of their ability to secrete growth factors essential for vascularization, whereas MNCs contain endothelial progenitor cells that are important for blood vessel formation. However, conventional methods for isolating these cells have limitations, especially in patients with diabetes with dysfunctional cells. To overcome this problem, a culture method called quality and quantity cultured peripheral blood MNCs (MNC-QQ) was developed to efficiently produce high-quality cells from small amounts of peripheral blood. Combining MSCs with MNC-QQs has been hypothesized to enhance therapeutic outcomes. This study aimed to examine the angiogenic efficacy of MSCs with MNC-QQs in models with severe lower limb ischemia. MethodsMNC-QQ was manufactured from the peripheral blood of healthy volunteers, while human bone marrow derived MSCs were purchased. To verify the effects of the MSC and MNC-QQs combination in angiogenesis, we conducted the HUVEC tube formation assay. For in vivo experiments, we created an ischemic limb model using BALB/c nude mice. Saline, MSCs alone, and a combination of MSCs and MNC-QQs were administered intramuscularly into the ischemic limbs. Blood flow was measured over time using laser doppler, and the ischemic limbs were harvested 21 days later for HE staining and immunostaining for histological assessment. ResultsIn-vitro studies demonstrated increased angiogenesis when MSCs were combined with MNC-QQs compared with MSCs alone. In vivo experiments using a mouse model of severe lower limb ischemia showed that combination therapy significantly improved blood flow recovery and limb salvage compared with MSCs alone or saline treatment. Histological analysis revealed enhanced vessel density, arteriogenesis, muscle regeneration, and reduced fibrosis in the MSC + MNC-QQ group compared with those in the saline group. Although the specific interactions between MSCs and MNC-QQs have not been fully elucidated, combined therapy leverages the benefits of both cell types, resulting in improved outcomes for vascular regeneration. ConclusionsThis study highlights the potential of the simultaneous transplantation of MSCs and MNC-QQs as a promising therapeutic approach for CLTI, offering sustained long-term benefits for patients.

Benefits of Combining Antiepileptic Drugs with Vitamin B12 on Redox Balance: Penicillin-Induced Experimental Epilepsy Model.

A combination of antiepileptic drugs and antioxidants may be an effective treatment by restoring the disrupted redox balance and reducing oxidative stress exposure to neurons. This study aims to evaluate the effects of valproate and vitamin B12 on oxidative stress in an experimental epilepsy model induced by penicillin when administered alone or in combination. 35 male Wistar rats were used in this study. The rats were divided into five groups, which were saline group, 1 mg/kg, 2 mg/kg Vit B12 groups and Sodium valproate group Sodium valproate + Vit B12 group. The epileptic activity was induced by 500 IU of penicillin injection. Sodium valproate and Vitamin B12 were administered 30 min after penicillin administration. Electrocorticogram recordings were taken for 2 hours post-treatment and serum parameters were assessed for oxidative stress markers using spectrophotometric method. There is statistically significant difference between the groups in total antioxidant status, total oxidant status, and oxidative stress index value (p=0.013; p˂0.001; p˂0.001, respectively). The valproate+vitamin B12 group showed elevated total thiol and native thiol levels, along with reduced disulphide levels, resulting in the lowest OSI value. These findings suggest the combined treatment effectively reduces oxidative stress. This study provides valuable insights into the antioxidant properties of valproate and vitamin B12, positioning them as potential agents for managing epilepsy. Understanding the efficacy and reliability of antioxidant strategies in epilepsy management could contribute significantly to advancements in epilepsy therapeutics.