Vantris vs. deflux for treatment of paediatric vesicoureteral reflux: Efficacy and obstruction risk.

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.

S100a10 deficiency in neutrophils aggravates ulcerative colitis in mice.

BACKGROUND AND AIMS: S100a10 is a member of the S100 family of proteins, which plays a key role in the depression and tumor metastasis. However, the role of S100a10 is unclear in ulcerative colitis. METHODS: The effect of S100a10 was assessed using a murine ulcerative colitis model which was accompanied by parameters including body weight loss, disease activity index, histological score, colon weight and length. The quantity and role of immune cells was determined by flow cytometry and bone marrow chimeric mice. Neutrophils depletion, adoptive cell transfer and conditional knockout mice were used to ascertain which cells played the key role in ulcerative colitis. The function of neutrophils was evaluated by migration assay, phagocytosis assay, multiplex immunoassay and real-time PCR. RESULTS: In this study, our data showed that S100a10-/- mice were prone to ulcerative colitis induced by dextran sodium sulfate. Neutrophils number increased in colon of S100a10-/- mice after dextran sodium sulfate treatment significantly. Meanwhile, adoptive transfer of neutrophils from wild type mice partially decreased the susceptibility of S100a10-/- mice to dextran sodium sulfate. There was no difference in ulcerative colitis between the groups of S100a10-/- mice without neutrophils and wild type mice. Finally, we found that S100a10-/- neutrophils had stronger function in secretion and synthesis of inflammatory factor. CONCLUSIONS: In one word, these results suggest that S100a10 has a role in inhibiting the pathogenesis of ulcerative colitis through regulation of neutrophils function.

Evaluation of anti-inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights.

BACKGROUND: Kaurenol, a diterpene alcohol found in Copaifera langsdorffii Desf. (known as "copaiba"), is historically used in traditional medicine for inflammatory conditions. OBJECTIVES: This study aims to comprehensively assess the potential anti-inflammatory and antinociceptive properties of kaurenol. METHODS: To this end, the following experiments were conducted to evaluated toxicity: locomotor performance and acute toxicity; nociception: acetic acid-induced writhing and formalin-induced antinociception; and anti-inflammatory activity: carrageenan and dextran-induced paw edema at 10, 20, and 40 mg/kg, and measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in macrophages at 1, 3, and 9 µg/ml. RESULTS: Kaurenol did not show significant locomotor changes, acute toxicity, and central analgesic activity in the first phase of formalin test at dosages tested. Kaurenol showed 53%, 64%, 64%, and 58% of inhibition in the acetic acid-induced writhing, second phase of formalin test, carrageenan and dextran-induced paw edema, respectively. CONCLUSION: The anti-inflammatory activity was associated with the regulation of NO release and probably with the regulation of mediators, such as serotonin and prostaglandin in vascular permeability, as well as by being associated with the regulation of IL-6 and IL-10. Kaurenol display anti-inflammatory activity but has no analgesic activity.

Effects of Huzhangoside C on Dextran Sodium Sulfate-Stimulated Colitis in Mice.

Chronic inflammation is a major risk factor for cancer. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, ultimately leading to a breakdown of intestinal barrier function. Clematis florida var. plena is a folk prescription used to treat inflammation and rheumatism in She pharmacy. The bioactivity of C. florida var. plena is primarily due to triterpene saponins. Huzhangoside C (HZ) is an active component of C. florida var. plena. In this study, the anti-inflammatory effect of HZ on a mouse colitis model induced by dextran sulfate sodium (DSS) was investigated. Result indicated a notable reduction in body weight loss and colon length shortening in HZ-mediated mice compared to DSS-stimulated control mice. Furthermore, inflammatory signaling mechanisms involving interleukin-6 and tumor necrosis factor-α were suppressed in HZ-treated mice. HZ treatment significantly suppressed the expression of nuclear factor kappa B (NF-κB), STAT3, and iNOS in colon tissue. After HZ treatment, malondialdehyde and nitric oxide levels were significantly decreased, while Nrf-2, superoxide dismutase, and glutathione expression levels were notably improved. The result indicated that HZ could activate the Nrf-2 signal cascade, inhibit the expression of NF-κB, eNOS, and STAT3, and enhance the intestinal barrier function of DSS stimulated ulcerative colitis intestinal injury. The results suggest that HZ is potential anti-inflammatory agent for treating IBD.

Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms.

The Vegetable 'Kale' Protects against Dextran-Sulfate-Sodium-Induced Acute Inflammation through Moderating the Ratio of Proinflammatory and Anti-Inflammatory LPS-Producing Bacterial Taxa and Augmenting the Gut Barrier in C57BL6 Mice.

Kale (Brassica oleracea var. acephala), a food rich in bioactive phytochemicals, prevents diet-induced inflammation and gut dysbiosis. We hypothesized that the phytochemicals protect against the lipopolysaccharide (LPS)-induced acute inflammation which results from gut dysbiosis and loss of gut barrier integrity. We designed this study to test the protective effects of the whole vegetable by feeding C57BL/6J mice a rodent high-fat diet supplemented with or without 4.5% kale (0.12 g per 30 g mouse) for 2 weeks before administering 3% dextran sulfate sodium (DSS) via drinking water. After one week, DSS increased the representation of proinflammatory LPS (P-LPS)-producing genera Enterobacter and Klebsiella in colon contents, reduced the representation of anti-inflammatory LPS (A-LPS)-producing taxa from Bacteroidales, reduced the expression of tight junction proteins, increased serum LPS binding protein, upregulated molecular and histopathological markers of inflammation in the colon and shortened the colons. Mice fed kale for 2 weeks before the DSS regime had a significantly reduced representation of Enterobacter and Klebsiella and instead had increased Bacteroidales and Gram-positive taxa and enhanced expression of tight junction proteins. Downstream positive effects of dietary kale were lack of granuloma in colon samples, no shortening of the colon and prevention of inflammation; the expression of F4/80, TLR4 and cytokines 1L-1b, IL-6, TNF-a and iNOS was not different from that of the control group. We conclude that through reducing the proliferation of P-LPS-producing bacteria and augmenting the integrity of the gut barrier, kale protects against DSS-induced inflammation.

Anti-Inflammatory Effect and Signaling Mechanism of Glycine max Hydrolyzed with Enzymes from Bacillus velezensis KMU01 in a Dextran-Sulfate-Sodium-Induced Colitis Mouse Model.

The purpose of this study was to investigate the effect that Glycine max hydrolyzed with enzymes from Bacillus velezensis KMU01 has on dextran-sulfate-sodium (DSS)-induced colitis in mice. Hydrolysis improves functional health through the bioconversion of raw materials and increase in intestinal absorption rate and antioxidants. Therefore, G. max was hydrolyzed in this study using a food-derived microorganism, and its anti-inflammatory effect was observed. Enzymatically hydrolyzed G. max (EHG) was orally administered once daily for four weeks before DSS treatment. Colitis was induced in mice through the consumption of 5% (w/v) DSS in drinking water for eight days. The results showed that EHG treatment significantly alleviated DSS-induced body weight loss and decreased the disease activity index and colon length. In addition, EHG markedly reduced tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and increased that of IL-10. EHG improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice. Moreover, we found that the abundance of 15 microorganisms changed significantly; that of Proteobacteria and Escherichia coli, which are upregulated in patients with Crohn's disease and ulcerative colitis, decreased after EHG treatment. These results suggest that EHG has a protective effect against DSS-induced colitis and is a potential candidate for colitis treatment.

Intestinal Epithelial Cell-Related Alternative Splicing Events in Dextran Sodium Sulfate-Induced Acute Colitis.

BACKGROUND: Alternative splicing of pre-messenger RNA is recognized as the crucial mechanism for gene expression regulation and proteome diversity generation. Alternative splicing has been found to be related to the pathogenesis of inflammatory bowel disease. The aim of this study was to identify the alternative splicing events in intestinal epithelial cells from mouse models of acute colitis and expand the understanding of the pathogenesis of inflammatory bowel disease. METHODS: The acute colitis mouse models were constructed, and intestinal epithelial cells of the colon were isolated for RNA sequence. The replicate Multivariate Analysis of Transcript Splicing software was used to analyze the alternative splicing events. The functional analysis was performed on genes with significant differential alternative splicing events. The alternative splicing events of picked genes were validated by reverse transcription polymerase chain reaction. RESULTS: A total of 340 significant differential alternative splicing events (from 293 genes) were screened out in acute colitis, and the alternative splicing events of CDK5-regulatory subunit associated protein 3 and TRM5 tRNA methyltransferase 5 were validated. The functional analysis showed that differential alternative splicing events in acute colitis participate in the apoptotic process, and the alternative splicing events of 3 genes (BCL2/adenovirus E1B-interacting protein 2, tumor necrosis factor receptor-associated factor 1, and tumor necrosis factor receptor-associated factor 7) were validated by reverse transcription polymerase chain reaction. CONCLUSION: This study pointed out the potential impact of different alternative splicing in acute colitis.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Intraoperative Infusion of Dextran Confers No Additional Benefit after Carotid Endarterectomy but Is Associated with Increased Perioperative Major Adverse Cardiac Events.

BACKGROUND: Intraoperative dextran infusion has been associated with reduction of an embolic risk in patients undergoing carotid endarterectomy (CEA). Nonetheless, dextran has been associated with adverse reactions, including anaphylaxis, hemorrhage, cardiac, and renal complications. Herein, we aimed to compare the perioperative outcomes of CEA stratified by the use of intraoperative dextran infusion using a large multiinstitutional dataset. METHODS: Patients undergoing CEA between 2008 and 2022 from the Vascular Quality Initiative database were reviewed. Patients were categorized by use of intraoperative dextran infusion, and demographics, procedural data, and in-hospital outcomes were compared. Logistic regression analysis was utilized to adjust for differences in patients while assessing the association between postoperative outcomes and intraoperative infusion of dextran. RESULTS: Of 140,893 patients undergoing CEA, 9,935 (7.1%) patients had intraoperative dextran infusion. Patients with intraoperative dextran infusion were older with lower rates of symptomatic stenosis (24.7% vs. 29.3%; P < 0.001) and preoperative use of antiplatelets, anticoagulants and statins. Additionally, they were more likely to have severe carotid stenosis (>80%; 49% vs. 45%; P < 0.001) and undergo CEA under general anesthesia (96.4% vs. 92.3%; P < 0.001), with a more frequent use of shunt (64.4% vs. 49.5%; P < 0.001). After adjustment, multivariable analysis showed that intraoperative dextran infusion was associated with higher odds of in-hospital major adverse cardiac events (MACE), including myocardial infarction [MI] (odds ratio [OR], 1.76, 95% confidence interval [CI]: 1.34-2.3, P < 0.001), congestive heart failure [CHF] (OR, 2.15, 95% CI: 1.67-2.77, P = 0.001), and hemodynamic instability requiring vasoactive agents (OR, 1.08, 95% CI: 1.03-1.13, P = 0.001). However, it was not associated with decreased odds of stroke (OR, 0.92, 95% CI: 0.74-1.16, P = 0.489) or death (OR, 0.88, 95% CI: 0.58-1.35, P = 0.554). These trends persisted even when stratified by symptomatic status and degree of stenosis. CONCLUSIONS: Intraoperative infusion of dextran was associated with increased odds of MACE, including MI, CHF, and persistent hemodynamic instability, without decreasing the risk of stroke perioperatively. Given these results, judicious use of dextran in patients undergoing CEA is recommended. Furthermore, careful perioperative cardiac management is warranted in select patients receiving intraoperative dextran during CEA.

GM-CSF-producing CCR2+ CCR6+ Th17 cells are pathogenic in dextran sodium sulfate-induced colitis model in mice.

Although excessive immune responses by Th17 cells, a helper T cell subset, are implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanism by which its localization in an inflamed colon is regulated remains unclear. Chemokines and their receptors are involved in the pathogenesis of IBD, however, the relative significance of each receptor on Th17 cells remains unknown. We generated C-C motif chemokine receptor 2 (CCR2) knockout (KO) and CCR6 KO mice in the syngeneic background using the CRISPR/Cas9 system and found that the phenotypes of experimental colitis worsened in both mutant mice. Surprisingly, the phenotype of colitis in CCR2/CCR6-double knockout (CCR2/6 DKO) mice was opposite to that of the single-deficient mice, with significantly milder experimental colitis (p < .05). The same was true for the symptoms in CCR6 KO mice, but not in wild type mice treated with a CCR2 inhibitor, propagermanium. Colonic CCR2+ CCR6+ Th17 cells produced a potentially pathogenic cytokine GM-CSF whose levels in the gut were significantly reduced in CCR2/6 DKO mice (p < .05). These results suggest that GM-CSF-producing CCR2+ CCR6+ Th17 cells are pathogenic and are attracted to the inflamed colon by either CCR2 or CCR6 gradient, which subsequently exacerbates experimental colitis in mice.

Deflux Calcification Leading to Delayed Obstruction and Loss of Renal Function: A Case Report.

Dextranomer/hyaluronic acid (Deflux) has been widely used in the treatment of vesicoureteral reflux in the pediatric population. It has demonstrated acceptable early efficacy with minimal morbidity. Early complications from Deflux have been reported to occur in approximately 1% of cases. However, late complications from Deflux use, including calcification and delayed ureteral obstruction, are less well understood. We present the case of an asymptomatic 11 year old girl with severe ipsilateral hydroureteronephrosis, identified nearly 8 years after treatment. This case details a rare instance of loss of renal function after Deflux use in a patient with no apparent risk factors.

Endoscopic treatment of symptomatic VUR disease after the renal transplantation: analysis of 49 cases.

BACKGROUND: To evaluate the outcome of endoscopic treatment for symptomatic vesicoureteral reflux (VUR) disease in renal transplantation patients and to determine the factors that were associated with the success rate of the treatment. METHODS: A total of 121 symptomatic VUR diseases diagnosed between 2014 and 2018 in 3560 renal transplant patients. The results of 49 VUR cases that presented with febrile urinary tract infection (UTI) and were hospitalized for antibiotic treatment were included in the study. Reflux was detected by voiding cystourethrogram and treatment was performed by endoscopic Deflux® injection. The result of endoscopic treatment was evaluated clinically by 3 months periods. RESULTS: The mean time between transplantation and endoscopic treatment was 59.6 (5-132) months, and the mean follow-up period after the endoscopic treatment was 14 (6-48) months, respectively. The success rate after the first injection was 59.1% (n = 29) and 67.3% (n = 33) after the second injection. One patient developed anuria, one patient febrile UTI and four patients developed minimal macroscopic hematuria after the procedure. CONCLUSIONS: Endoscopic treatment of symptomatic VUR in transplanted kidney is a safe and feasible procedure. The amount of bulking agent or duration between the transplantation and diagnosis of VUR does not have any impact on the success of the treatment. However, the younger age of the patients and the female gender seem to have a positive effect on the outcome of the procedure.

Ultrasound-guided fine-needle aspiration of a rectal submucosal nodule.

Although endoscopic biopsy of a rectal submucosal nodule may be nondiagnostic, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be an important tool to make diagnosis. We report a case of a female patient who had an EUS-FNA of a submucosal nodule after a nondiagnostic rectal biopsy. The original diagnosis was erroneously rendered as concerning for necrotic neoplasm. The correct diagnosis of Solesta-induced foreign body reaction was made on reviewing the slides once the history of remote Solesta injection was made available. This case illustrates the pathognomonic features of Solesta-induced rectal nodule and underscores the importance of detailed history as well as inclusion of iatrogenic diseases in the differential to prevent erroneous diagnosis and management. Potential pitfalls in cytopathological diagnosis are discussed.

Ureteral Obstruction After Endoscopic Treatment of Vesicoureteral Reflux: Does the Type of Injected Bulking Agent Matter?

PURPOSE OF REVIEW: Endoscopic injection of bulking agents for the treatment of vesicoureteral reflux (VUR) has become a therapeutic alternative to antibiotic prophylaxis and ureteral reimplantation. Although considered as a safe and efficient procedure, several studies have reported cases of ureteral obstruction (UO) after endoscopic correction of VUR. This review article evaluates the present VUR literature to estimate the incidence of UO following endoscopic injection of different substances, while also discussing the impact of injection technique and implant volume. RECENT FINDINGS: Twenty-five publications were identified that provided detailed information on 64 females and 32 males (age range, 7 months-48 years) that developed UO after endoscopic treatment of VUR using dextranomer/hyaluronic acid (Dx/HA), polyacrylate polyalcohol (PP), polydimethylsiloxane (PDMS), calcium hydroxyapatite (CaHA), polytetrafluoroethylene (PTFE), or collagen. There was some variation in the reported incidence of UO among these materials: Dx/HA (0.5-6.1%), PP (1.1-1.6%), PDMS (2.5-10.0%), CaHA (1.0%), and PTFE (0.3%). Postoperative UO was described following subureteric transurethral injection (STING), intraureteric hydrodistension implantation technique (HIT), combined HIT/STING and double HIT. The injected volume ranged widely, also depending on the type of bulking agent: Dx/HA (0.3-3.0 mL), PP (0.3-1.2 mL), PDMS (1.0-2.2 mL), CaHA (0.4-0.6 mL), and PTFE (1.5-2.0 mL). The timing of UO varied from immediately after the procedure to 63 months. Over half of patients showed asymptomatic hydroureteronephrosis on follow-up imaging, whereas the remaining presented with symptoms of acute UO or fever. UO remains a rare complication after endoscopic correction of VUR, generally reported in less than 1% of treated cases, which appears to be independent of the injected substance, volume, and technique. However, long-term follow-up is recommended as asymptomatic or delayed UO can occur, potentially leading to deterioration of renal function.

Systemic exposure to a single dose of ferucarbotran aggravates neuroinflammation in a murine model of experimental autoimmune encephalomyelitis.

BACKGROUND: Medicinal preparations of iron oxide nanoparticles (IONPs) have been used as MRI contrast agents for the diagnosis of hepatic tumors and the assessment of neuroinflammation and blood-brain barrier integrity. However, it remains mostly unclear whether exposure to IONPs affects neuroinflammation under disease conditions. The present study aims to investigate the impact of IONPs on autoimmune-mediated neuroinflammation using a murine model of experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis. METHODS: Mice were either left untreated or immunized with myelin oligodendrocyte glyco-protein on day 0 followed by two injections of pertussis toxin for EAE induction. The EAE mice were intravenously administered with a single dose of the carboxydextran-coated IONPs, ferucarbotran (20 mg Fe/kg) and/or saline (as vehicle) on day 18. Symptoms of EAE were daily monitored until the mice were killed on day 30. Tissue sections of the brain and spinal cord were prepared for histopathological examinations. Iron deposition, neuron demyelination and inflammatory cell infiltration were examined using histochemical staining. The infiltration of microglial and T cells, and cytokine expression were examined by immunohistochemical staining and/or reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Iron deposition was detected in both the brain and spinal cord of EAE mice 3 days post-ferucarbotran treatment. The clinical and pathological scores of EAE, percentage of myelin loss and infiltration of inflammatory cells into the spinal cord were significantly deteriorated in EAE mice treated with ferucarbotran. Furthermore, ferucarbotran treatment increased the number of CD3+, Iba-1+, IL-6+, Iba-1+TNF-α+ and CD3+IFN-γ+ cells in the spinal cord of EAE mice. CONCLUSION: A single exposure to ferucarbotran exacerbated neuroinflammation and disease severity of EAE, which might be attributed to the enhanced activation of microglia and T cells. These results demonstrated that the pro-inflammatory effect of ferucarbotran on the central nervous system is closely associated with the deterioration of autoimmunity.

Evaluation of DMSO dextrose as a suitable alternative for DMSO dextran in cord blood cryopreservation.

BACKGROUND AND OBJECTIVES: Umbilical cord blood is considered an alternative source of hematopoietic stem cells. Standard banking procedures use 50/55% DMSO in dextran 40 for cryopreservation and dextran-based solutions for thawing, however, due to the potential risk of crystallization of dextran, dextran 40 approved for clinical use has become limited or unavailable. This affects cryopreservation and thawing procedures. Carbohydrates, in particular sucrose, trehalose and glucose, have been shown to be effective in reducing cell damage during dehydration and have cryoprotective potential. We aim to study a 50/55% DMSO in 5% dextrose cryopreservation solution as an alternative to DMSO dextran. MATERIALS AND METHODS: Eighteen samples were divided into two aliquots and cryopreserved, one using standard solution and the other with DMSO dextrose experimental solution. Both aliquots were thawed and diluted with PBS or saline. Total nucleated cells counts, 7-AAD viability of CD45+ cells and recovery of CD34+ viable cells were assessed on thawed samples and compared between pair of aliquots. RESULTS: No differences were observed in the total nucleated cells recovery between cryopreservation solutions, however, higher viability and CD34+ viable cells recoveries were observed using the experimental solution. CONCLUSION: Results showed that DMSO dextrose cryopreservation solution had better results than the standard solution when thawed in an isotonic solution. This indicates that DMSO dextrose is probably a better alternative for direct infusion or when dextran thawing solutions are unavailable. Viability of CD45+ cells and recovery of CD34+ viable cells have positive correlation with engraftment, highlighting the relevance of the optimization of the cryopreservation and thawing process.

Hydrocephalus after Intrathecal Administration of Dextran to Rhesus Macaques (Macaca mulatta).

Dextrans have been used extensively as medical therapies and labeling agents in biomedical research to investigate the blood-brain barrier and CSF flow and absorption. Adverse effects from dextrans include anaphylactic reaction and dilation of the cerebral ventricles due to administration into the subarachnoid space. This retrospective study describes 51 rhesus macaques (Macaca mulatta) that received dextran intrathecally. The purpose of intrathecal administration was to enable detection of long-lived, dextran-labeled macrophages and to study monocyte-macrophage turnover in the CNS of SIV- or SHIV- infected and uninfected animals by using immunofluorescence. Of the 51 dextran-treated macaques, 8 that received dextran diluted in saline developed hydrocephalus; 6 of these 8 animals exhibited neurologic signs. In contrast, none of the macaques that received intrathecal dextran diluted in PBS developed hydrocephalus. These data suggest the use of saline diluent and the duration of dextran exposure as potential factors contributing to hydrocephalus after intrathecal dextran in rhesus macaques.

Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging.

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration.