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Biomedical subjects

Yan Lu

Publications and source records attributed to Yan Lu.

At least 37 records · Page 2Linked to original sources

Accurate haplotype inference for multiple linked single-nucleotide polymorphisms using sibship data.

Sibships are commonly used in genetic dissection of complex diseases, particularly for late-onset diseases. Haplotype-based association studies have been advocated as powerful tools for fine mapping and positional cloning of complex disease genes. Existing methods for haplotype inference using data from relatives were originally developed for pedigree data. In this study, we proposed a new statistical method for haplotype inference for multiple tightly linked single-nucleotide polymorphisms (SNPs), which is tailored for extensively accumulated sibship data. This new method was implemented via an expectation-maximization (EM) algorithm without the usual assumption of linkage equilibrium among markers. Our EM algorithm does not incur extra computational burden for haplotype inference using sibship data when compared with using unrelated parental data. Furthermore, its computational efficiency is not affected by increasing sibship size. We examined the robustness and statistical performance of our new method in simulated data created from an empirical haplotype data set of human growth hormone gene 1. The utility of our method was illustrated with an application to the analyses of haplotypes of three candidate genes for osteoporosis.

Algorithms↗

Lipid mediator informatics and proteomics in inflammation resolution.

Lipid mediator informatics is an emerging area denoted to the identification of bioactive lipid mediators (LMs) and their biosynthetic profiles and pathways. LM informatics and proteomics applied to inflammation, systems tissues research provides a powerful means of uncovering key biomarkers for novel processes in health and disease. By incorporating them with system biology analysis, we review here our initial steps toward elucidating relationships among a range of bimolecular classes and provide an appreciation of their roles and activities in the pathophysiology of disease. LM informatics employing liquid chromatography-ultraviolet-tandem mass spectrometry (LC-UV-MS/MS), gas chromatography-mass spectrometry (GC-MS), computer-based automated systems equipped with databases and novel searching algorithms, and enzyme-linked immunosorbent assay (ELISA) to evaluate and profile temporal and spatial production of mediators combined with proteomics at defined points during experimental inflammation and its resolution enable us to identify novel mediators in resolution. The automated system including databases and searching algorithms is crucial for prompt and accurate analysis of these lipid mediators biosynthesized from precursor polyunsaturated fatty acids such as eicosanoids, resolvins, and neuroprotectins, which play key roles in human physiology and many prevalent diseases, especially those related to inflammation. This review presents detailed protocols used in our lab for LM informatics and proteomics using LC-UV-MS/MS, GC-MS, ELISA, novel databases and searching algorithms, and 2-dimensional gel electrophoresis and LC-nanospray-MS/MS peptide mapping.

Algorithms↗

Lipid mediator informatics-lipidomics: novel pathways in mapping resolution.

Lipidomics, the systematic decoding of lipid-based information in biosystems, is composed of identifying and profiling lipids and lipid-derived mediators. As currently practiced, lipidomics can be subdivided into architecture/membrane lipidomics and mediator lipidomics. The mapping of structural components and their relation to cell activation as well as generation of potent lipid mediators and networks involves a mass spectrometry-computational approach so that interrelationships and complex mediator networks important for cell homeostasis can be appreciated. Cell membranes are composed of a bilayer that contains phospholipids, fatty acids, integral membrane proteins, membrane-associated proteins, sphingolipids, and so on. The membrane composition of many cell types has been established. The components' organization and effect on cell function remains to be established, however, and is a quest for lipidomics. Here, we review liquid chromatography tandem mass spectrometry-based lipidomic analyses to address bioactive lipid mediators in signaling pathways and the roles of lipid-derived mediators in resolution of inflammation.

Animals↗

Transforming growth factor-beta1 induces the non-classical secretion of peroxiredoxin-I in A549 cells.

Recent studies found that peroxiredoxin-I (Prx-I) is secreted from A549 cells although it does not contain a signal peptide and is known to be a cytosolic protein. Transforming growth factor-beta1 (TGF-beta1) treatment dramatically enhanced Prx-I secretion from A549 cells, and this effect was not inhibited by brefeldin A. Further investigation revealed that A549 cells constitutively secrete TGF-beta1. Furin, a TGF-beta1-converting enzyme, was also highly activated in A549 cells. Ectopic expression of alpha(1)-antitrypsin Portland (alpha(1)-PDX), a potent furin inhibitor, blocked both TGF-beta1 activation and Prx-I secretion. Our findings collectively suggest that non-classical secretion of Prx-I is induced by TGF-beta1, which is constitutively activated by furin in A549 cells.

Adenocarcinoma↗

Cellular and organ level localization of maltose in maltose-excess Arabidopsis mutants.

Maltose is the predominant form of carbon exported from the chloroplast at night. Plants that lack either the chloroplast maltose transporter or disproportionating enzyme 2 (DPE2, EC 2.4.1.25) have excess maltose in leaves. We confirmed that DPE2 is not associated with the chloroplast in Arabidopsis thaliana. Using non-aqueous fractionation methods, we found that essentially all the maltose in mex1-1 leaves is located inside chloroplasts but only 40% of maltose in dpe2-1 leaves is located inside chloroplasts. We found that maltose exists in a significant amount in the exudates collected from maltose-accumulating dpe2-1 Arabidopsis petioles. However, the amount of maltose in the exudates from mex1-1 petioles was not significantly different from that in wild-type phloem exudates. We found twice as much maltose in the roots of dpe2-1 plants relative to wild type but the maltose level in the roots of mex1-1 plants was not higher than wild type. We conclude that maltose accumulated in the cytosol of leaves can be carried from the shoots to the roots and that maltose accumulated in the chloroplast of mex1-1 leaves is not mobilized. By measuring the transcript levels and enzymatic activities, we show that maltose-metabolizing enzymes are active in wild-type roots. The amount of maltose moved from the shoots to the roots increased in dpe2-1 plants. The roots of dpe2-1 plants must have the capacity to metabolize the excess maltose.

Arabidopsis↗

Thermosensitive core-shell particles as carrier systems for metallic nanoparticles.

We present a new system that allows us to modulate the catalytic activity of metal nanoparticles (Ag) by a thermodynamic transition that takes place within the carrier system. Thermosensitive core-shell particles have been used as the carrier system in which the core consists of poly(styrene) (PS), whereas the shell consists of a poly(N-isopropylacrylamide) (PNIPA) network cross-linked by N,N'-methylenebisacrylamide (BIS). Immersed in water, the shell of these particles is swollen. Heating the suspension above 32 degrees C leads to a volume transition within the shell that is followed by a marked shrinking of the network of the shell. The maximum degree of swelling can be adjusted by the degree of cross-linking. Silver nanoparticles with diameters ranging from 6.5 to 8.5 nm have been embedded into thermosensitive PNIPA networks with different cross-linking densities. The Ag nanoparticles do not influence the swelling and the shrinking of the network in the shell. The surface plasmon absorption band of the nanoparticles is shifted to higher wavelengths with temperature. This is traced back to the varying distance of the nanoparticles caused by the swelling and the shrinking of the shell. The catalytic activity is investigated by monitoring photometrically the reduction of 4-nitrophenol by an excess of NaBH4 in the presence of the silver nanocomposite particles. The rate constant kapp was found to be strictly proportional to the total surface of the nanoparticles in the system. Moreover, kapp is first decreasing with increasing temperature when approaching the volume transition. This is due to the strong shrinking of the network. Only at temperatures above the volume transition is the normal Arrhenius-type dependence of kapp found again. In this way, catalytic activity of the metal nanoparticles enclosed in a "nanoreactor" can be modulated by volume transition over a wide range.

Journal Article↗

Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury.

BACKGROUND: The beneficial effects of reperfusion therapies have been limited by the amount of ischemic damage that occurs before reperfusion. To enable development of interventions to reduce cell injury, our research has focused on understanding mechanisms involved in cardiac cell death after ischemia/reperfusion (I/R) injury. In this context, our laboratory has been investigating the role of the receptor for advanced-glycation end products (RAGE) in myocardial I/R injury. METHODS AND RESULTS: In this study we tested the hypothesis that RAGE is a key modulator of I/R injury in the myocardium. In ischemic rat hearts, expression of RAGE and its ligands was significantly enhanced. Pretreatment of rats with sRAGE, a decoy soluble part of RAGE receptor, reduced ischemic injury and improved functional recovery of myocardium. To specifically dissect the impact of RAGE, hearts from homozygous RAGE-null mice were isolated, perfused, and subjected to I/R. RAGE-null mice were strikingly protected from the adverse impact of I/R injury in the heart, as indicated by decreased release of LDH, improved functional recovery, and increased adenosine triphosphate (ATP). In rats and mice, activation of the RAGE axis was associated with increases in inducible nitric oxide synthase expression and levels of nitric oxide, cyclic guanosine monophosphate (cGMP), and nitrotyrosine. CONCLUSIONS: These findings demonstrate novel and key roles for RAGE in I/R injury in the heart. The findings also demonstrate that the interaction of RAGE with advanced-glycation end products affects myocardial energy metabolism and function during I/R.

Animals↗

A gene expression signature that can predict green tea exposure and chemopreventive efficacy of lung cancer in mice.

Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Previously, we found that treatment of A/J mice with either green tea (0.6% in water) or a defined green tea catechin extract (polyphenon E; 2.0 g/kg in diet) inhibited lung tumor tumorigenesis. Here, we described expression profiling of lung tissues derived from these studies to determine the gene expression signature that can predict the exposure and efficacy of green tea in mice. We first profiled global gene expressions in normal lungs versus lung tumors to determine genes which might be associated with the tumorigenic process (TUM genes). Gene expression in control tumors and green tea-treated tumors (either green tea or polyphenon E) were compared to determine those TUM genes whose expression levels in green tea-treated tumors returned to levels seen in normal lungs. We established a 17-gene expression profile specific for exposure to effective doses of either green tea or polyphenon E. This gene expression signature was altered both in normal lungs and lung adenomas when mice were exposed to green tea or polyphenon E. These experiments identified patterns of gene expressions that both offer clues for green tea's potential mechanisms of action and provide a molecular signature specific for green tea exposure.

Algorithms↗

Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes.

Protectin D1, neuroprotectin D1 when generated by neural cells, is a member of a new family of bioactive products generated from docosahexaenoic acid. The complete stereochemistry of protectin D1 (10,17S-docosatriene), namely, chirality of the carbon-10 alcohol and geometry of the conjugated triene, required for bioactivity remained to be assigned. To this end, protectin D1/neuroprotectin D1 (PD1) generated by human neutrophils during murine peritonitis and by neural tissues was separated from natural isomers and subjected to liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Comparisons with six 10,17-dihydroxydocosatrienes prepared by total organic and biogenic synthesis showed that PD1 from human cells carrying potent bioactivity is 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Additional isomers identified included trace amounts of Delta15-trans-PD1 (isomer III), 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid (isomer IV), and a double dioxygenation product 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid (isomer I), present in exudates. 18O2 labeling showed that 10S,17S-diHDHA (isomer I) carried 18O in the carbon-10 position alcohol, indicating sequential lipoxygenation, whereas PD1 formation proceeded via an epoxide. PD1 at 10 nM attenuated (approximately 50%) human neutrophil transmigration, whereas Delta15-trans-PD1 was essentially inactive. PD1 was a potent regulator of polymorphonuclear leukocyte (PMN) infiltration (approximately 40% at 1 ng/mouse) in peritonitis. The rank order at 1- to 10-ng dose was PD1 approximately PD1 methyl ester >> Delta15-trans-PD1 > 10S,17S-diHDHA (isomer I). 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid (isomer VI) proved > or = PD1 in blocking PMN infiltration, but was not a major product of leukocytes. PD1 also reduced PMN infiltration after initiation (2 h) of inflammation and was additive with resolvin E1. These results indicate that PD1 is a potent stereoselective anti-inflammatory molecule.

Animals↗

Metal-ion interactions with sugars. Crystal structure and FT-IR study of PrCl3-D-ribose complex.

A single-crystal of PrCl3.D-ribose.5H2O was obtained from a methanol-water solution and its structure determined by X-ray crystallography. Two configurations of the complex, as a pair of isomers, were found in the single-crystal in a disordered state, which differs from that reported previously. The ligand of one of the complexes is alpha-D-ribopyranose in the 4C1 conformation, and the ligand of the other is beta-D-ribopyranose in the 1C4 conformation. The alpha:beta anomeric ratio is 54:46. Both ligands of the two isomers provide three hydroxyl groups in an axial-equatorial-axial orientation for coordination. The Pr3+ ion is nine-coordinated, with five Pr-O bonds from water molecules, three Pr-O bonds from the hydroxyl groups of the D-ribopyranose and one Pr-Cl bond from chloride ion. The hydroxyl groups, water molecules, and chloride ions form an extensive hydrogen-bond network. The IR spectral C-C, O-H, C-O, and C-O-H vibrations are shifted in the complex, compared to those in d-ribose, and the IR results are in accord with those obtained from the X-ray diffraction study.

Crystallography, X-Ray↗

Metal-ion interactions with carbohydrates. Crystal structure and FT-IR study of the SmCl3-ribose complex.

A single-crystal of SmCl3.C5H10O5.5H2O was obtained from methanol-water solution and its structure determined by X-ray. Two forms of the complex as a pair of anomers and related conformers were found in the single-crystal in a disordered state. One ligand is alpha-D-ribopyranose in the 4C1 conformation and the other one is beta-D-ribopyranose. The anomeric ratio is 1:1. Both ligands provide three hydroxyl groups in ax-eq-ax orientation for coordination. The Sm3+ ion is nine-coordinated with five Sm-O bonds from water molecules, three Sm-O bonds from hydroxyl groups of the D-ribopyranose and one Sm-Cl bond. The hydroxyl groups, water molecules and chloride ions form an extensive hydrogen-bond network. The IR spectral C-C, O-H, C-O, and C-O-H vibrations were observed to be shifted in the complex and the IR results are in accord with those of X-ray diffraction.

Carbohydrate Conformation↗

Efficacy of the farnesyltransferase inhibitor R115777 in a rat mammary tumor model: role of Ha-ras mutations and use of microarray analysis in identifying potential targets.

Rats treated with the alkylating agent methylnitrosourea (MNU) develop multiple, hormonally dependent mammary tumors. Roughly 50% of the tumors have Ha-ras mutation, whereas 50% do not. The MNU-induced rat mammary tumor model was employed to examine the therapeutic efficacy of the farnesyltransferase inhibitor (FTI), R115777, and to examine the use of genomics in identifying susceptible tumors as well as identifying genes whose expression are modulated by FTI treatment. In animals bearing palpable mammary tumors (< 7 mm diameter), we performed a surgical biopsy, and 3 days following the biopsy, rats were treated with R115777 (50 mg/kg body wt/day) by gavage. Tumors with Ha-ras mutations underwent profound regression, with nearly 90% showing complete regressions within 4 weeks. In contrast, the non-Ha-ras mutation-bearing tumors yielded a more variable response, although roughly half of the non-Ha-ras mutation tumors underwent significant regression. These results show that although all tumors appear to respond to the FTI inhibitor the tumors with Ha-ras mutations were exquisitely sensitive. We employed a microarray approach to define potential targets and the mechanism of action of R115777 in Ha-ras mutant or wildtype tumors following treatment with FTI. In addition, we determined whether gene expression prior to FTI treatment can be used to differentiate highly sensitive tumors (Ha-ras mutant) and tumors with variable sensitivity (Ha-ras wildtype). Untreated or FTI-treated (4 days at 50 mg/kg body wt) tumors (Ha-ras mutant or wildtype) were examined using oligonucleotide arrays. A significant number of genes were differentially expressed in control rat mammary tumors with or without an activated Ha-ras mutation, suggesting that a microarray analysis might differentiate highly sensitive and variably sensitive tumors. Most of the genes whose expressions were modulated by FTI in tumors were independent of Ha-ras status and were presumably modulated by effects on farnesylation of proteins other than Ha-ras. However, treatment of Ha-ras-mutated mammary tumors with R155777 results in preferential modulation of genes involved in ras-MAP kinase signal transduction pathway and in decreased expression of many genes involved with cell proliferation. In contrast, several classes of genes are altered in rat mammary tumors without a mutated Ha-ras, suggesting that non-ras targets are involved. Ras pathway related genes, p53, WT1 and PCNA, were preferentially modulated in Ha-ras-mutated tumors, whereas modulation of genes in the G-protein pathway, various cytochrome p450s and RB1 are involved in Ha-ras wildtype tumors. Elucidation of gene expression changes in FTI-treated or control rat mammary adenocarcinomas will help in identifying potential pharmacodynamic markers of FTI treatment as well as potential molecular targets of R115777 and other FTIs.

Alkylating Agents↗

Enhanced DNA vaccine potency by mannosylated lipoplex after intraperitoneal administration.

BACKGROUND: Here we describe a novel DNA vaccine formulation that can enhance cytotoxic T lymphocyte (CTL) activity through efficient gene delivery to dendritic cells (DCs) by mannose receptor-mediated endocytosis. METHODS: Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. Mannosylated cationic liposomes (Man-liposomes) were prepared using cholesten-5-yloxy-N-{4-[(1-imino-2-D-thiomannosylethyl)amino]butyl}formamide (Man-C4-Chol) with cationic lipid. The potency of the mannosylated liposome/pCMV-OVA complex (Man-lipoplex) was evaluated by measuring OVA mRNA in CD11c+ cells, CTL activity, and the OVA-specific anti-tumor effect after in vivo administration. RESULTS: An in vitro study using DC2.4 cells demonstrated that Man-liposomes could transfect pCMV-OVA more efficiently than cationic liposomes via mannose receptor-mediated endocytosis. In vivo studies revealed that the Man-lipoplex exhibited higher OVA mRNA expression in CD11c+ cells in the spleen and peritoneal cavity and provided a stronger OVA-specific CTL response than intraperitoneal (i.p.) administration of the conventional lipoplex and intramuscular (i.m.) administration of naked pCMV-OVA, the standard protocol for DNA vaccination. Pre-immunization with the Man-lipoplex provided much better OVA-specific anti-tumor effect than naked pCMV-OVA via the i.m. route. CONCLUSIONS: These results suggested that in vivo active targeting of DNA vaccine to DCs with Man-lipoplex might prove useful for the rational design of DNA vaccine.

Animals↗

In vivo study on the short-term effect of radiofrequency energy on chondromalacic patellar cartilage and its correlation with calcified cartilage pathology in an equine model.

Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, each patella was randomly assigned to one of four experimental groups: sham operated, untreated control; MD; bRFE; and mRFE. Animals were euthanized 6 months after treatment and fresh osteochondral sections were collected from the treated area, the border of the chondromalacic and nonchondromalacic area, and from two untreated areas for analysis of mechanical properties. The same areas were harvested from an additional six untreated ponies. The aggregate modulus (H(A)), Poisson's ratio (nu(s)), and permeability (k) were determined for each area under creep indentation, and cartilage thickness was measured with a needle probe. The relation between zone of calcified cartilage (ZCC) and mechanical properties of hyaline cartilage (HC) was assessed histomorphometrically. Treated areas of all four groups had inferior mechanical properties compared at the same location. The treated and border areas had significantly lower H(A) values than the untreated areas. Permeability values showed significant differences between bRFE and other treated groups. Chondromalacic areas showed thinning of cartilage compared to nonchondromalacic areas. Biomechanical properties of the injured cartilage were inferior to nonchondromalacic cartilage regardless of the treatment type. mRFE had the highest stiffness value compared to other treatments and significantly higher values than MD. A significant correlation was observed between the mechanical properties of HC and ZCC thickness.

Animals↗

Development of partial thickness articular cartilage injury in an ovine model.

The purpose of this study was to create a controlled partial thickness cartilage lesion in a sheep model, and to provide a foundation to study the natural history of the progression of this lesion. Twenty-eight sheep divided into four groups (1, 12, 24, and 52 weeks, n=7/group) were used in this study. In one stifle, a mechanical tool was used to create a 200 microm partial thickness lesion (1.5x1.5 cm2) on the medial femoral condyle via arthroscopy. Joint fluid was drawn presurgery and after euthanasia for analysis of collage II 3/4 C (long) (C2C). After euthanasia, the condyle was analyzed by gross appearance, confocal laser microscopy (CLM) for cell viability, scanning electronic microscopy (SEM) for surface roughness, Artscan for cartilage stiffness, and histology for cartilage morphology. The gross appearance of the treated area appeared rough, soft, and swollen compared to untreated control over time. CLM demonstrated that the depth of cell death increased to 590 microm at 52 weeks after surgery. SEM demonstrated that the treated area became more irregular over time. Stiffness of the treated area was significantly less than control by 12 weeks after surgery. Histologic analysis demonstrated that the 12, 24, and 52 week groups had significantly poorer histologic scores than the 1 week group. Joint fluid analysis demonstrated that the treatment group at 1 week had significant higher levels of C2C than the pretreatment baseline data. The results of this study demonstrated that partial thickness injury of cartilage continued to propagate and degenerate over time in this sheep model. Options for the prevention or treatment of this lesion may be tested using this model in the future.

Animals↗

Tests of linkage and association of PTH/PTHrP receptor type 1 gene with bone mineral density and height in Caucasians.

Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.S. Caucasian population, we tested linkage or association of the PTHR1 gene with BMD and height. Altogether, 1873 subjects from 405 Caucasian nuclear families were studied. BMD was measured at the lumbar spine (L1-L4) and total hip (femoral neck, trochanter, and intertrochanter regions). Four single nucleotide polymorphisms (SNPs) in the PTHR1 gene were genotyped. Sixteen haplotypes were reconstructed. Only two major haplotypes had frequencies >3% and were thus used for the analysis. Analyses were performed for BMD and height in the total sample and for peak BMD (PBMD) achieved in offspring subjects aged 20-50 in a subsample of 387 nuclear families. We found suggestive evidence for total association between haplotype 13 (AATG) and hip PBMD (P = 0.031). For height, evidence of within-family association was suggested for SNP1, SNP2, and haplotype 4 (GGCA) (P < or = 0.05). Our findings suggest that the PTHR1 gene may be important for PBMD, height variation, or both, although the significance is dampened by correction for multiple testing.

Absorptiometry, Photon↗

An ex vivo thermal chondroplasty model: the association of a char-like layer and underlying cell death.

PURPOSE: The purpose of this study was to evaluate the relation between the char-like layer observed during radiofrequency energy (RFE) treatment of cartilage and the depth of underlying cell death. METHODS: Healthy adult bovine patellae were treated with a monopolar RFE probe ex vivo at generator settings of 20, 30, 40, 50, 60, 80, and 110 in cut mode. The presence or absence of a char-like layer and visual electrical discharge was noted. Treated tissue was incubated with cell viability stain, and the depth of cell death and matrix debridement was measured from confocal laser microscopy images. RESULTS: At generator settings of 60 and above, a char-like layer, electrical discharge, and matrix debridement were consistently observed, and the depth of cell death was significantly less (P < .05) than when these features were not observed (< or =30). Paradoxically, the least depth of cell death did not occur at the lowest generator setting in cut mode. It occurred at a generator setting of 60. An increase in impedance of the system and a decrease in current were also associated with reduced cell death. CONCLUSIONS: In this controlled ex vivo study formation of a char-like layer, visual electrical discharge, increased impedance, and reduced current were associated with less depth of cell death when cartilage was treated with monopolar RFE. CLINICAL RELEVANCE: This study suggests that a char-like layer and electrical discharge during RFE treatment of cartilage may be advantageous because, potentially, these features are associated with less depth of cell death (safety) and greater matrix debridement (efficacy).

Animals↗