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Biomedical subjects

W Fan

Publications and source records attributed to W Fan.

At least 19 recordsLinked to original sources

Prevalence and estimated incidence of blood-borne viral pathogen infection in organ and tissue donors from northern Alberta.

To determine the potential safety benefit of introducing nucleic acid testing (NAT) in tissue and organ donors, the risk of virus transmission was examined in a Canadian population. Anonymous data on Northern Alberta tissue and organ donors from 1998 to 2004 were used to determine the seroprevalence and estimate the seroincidence and residual risk of HIV, HBV, HCV and HTLV infection. Of the 3372 donors identified, 71.1% were surgical bone, 13.2% were living organ and 15.6% were deceased organ/tissue donors. Seroprevalence was: HIV 0.00%, HBV 0.09%, HCV 0.48% and HTLV 0.03%. Incidence (/100,000 p-yrs) and residual risks (/100,000 donors) could only be estimated for HBV (24.2 and 3.9) and HCV (11.2 and 2.2). Risk estimates were higher for deceased donors than surgical bone donors. HCV had the highest prevalence and HBV had the highest estimated incidence. HIV and HTLV risks were extremely low precluding accurate quantification. In this region of low overall viral prevalence, HCV NAT would be most effective in deceased organ donors. In surgical bone donors the cost of implementing NAT is high without significant added safety benefit.

Adolescent↗

Evaluation of the accuracy of three electronic apex locators using glass tubules.

AIM: To evaluate the accuracy of three different electronic apex locators (EALs) using glass tubules. METHODOLOGY: Forty-eight glass tubules with different diameters and an agar model were used to mimic root canals. A size 15 stainless steel K-file was used as the measuring electrode. The Root ZX, Propex and Neosono Ultima EZ were used to measure the tubule length with tubules dry, or filled with 0.9% NaCl, 3% H(2)O(2), 2.5% NaOCl or 17% EDTA. The distance between the real length (RL) and measured length (ML) of the tubules was recorded. The range of RL +/- 0.5 mm and RL +/- 1 mm was used to evaluate the accuracy of the EALs. Results were subject to correlation analysis and Friedman's test. RESULTS: In dry tubules, the accuracy of Root ZX was 75-91.7% for RL +/- 0.5 mm and 100% for RL +/- 1 mm, whilst the measurements of the other two EALs were all within the RL +/- 0.5 mm. No influence from the increase in tubule diameter on the accuracy of all three EALs was observed in dry tubules. In tubules filled with electrolyte, the accuracy of the Root ZX decreased as tubule diameter increased (R(d) > 0, P < 0.05). The RL-ML distance recorded by Propex was inversely related to the tubule diameter (R(d) < 0, P < 0.05). The accuracy of Propex was 75-100% for RL +/- 0.5 mm and 100% for RL +/- 0.5 mm when the tubule diameter was not more than 0.80 mm, but decreased in tubules with diameter over 0.80 mm and filled with 2.5% NaOCl or 17% EDTA. Nearly, all the measurements (except for six tubules) using Neosono Ultima EZ were within 1 mm shorter than RL despite the contents in tubules and the increase of tubule diameter. CONCLUSIONS: The accuracy of the Root ZX decreased as the tubule diameter increased when tubules were filled with electrolytes. The electrolytes in the tubules decreased the accuracy of Propex when the tubule diameter was large. The electrolytes in tubules and tubule diameter had no influence on the accuracy of Neosono Ultima EZ. The Propex and Neosono Ultima EZ were more accurate than the Root ZX under various conditions in this laboratory study.

Chelating Agents↗

Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia.

OBJECTIVE: To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB) in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study design. METHODS: Subjects with CD who had a previous response from BoNTA were randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of clinical effect or completion of 20 weeks of observation. CD severity was measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and adverse events were assessed by structured interview. Statistical analysis included Wilcoxon rank sum test, log rank tests, and Kaplan-Meier survival curves for duration of effect. RESULTS: A total of 139 subjects (BoNTA, n = 74; BoNTB, n = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at 4 weeks after injection and did not differ between serotypes. Dysphagia and dry mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p = 0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders, BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1 weeks, p = 0.033). CONCLUSION: Both serotypes of botulinum toxin (BoNTA and BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks. BoNTA had fewer adverse events and a marginally longer duration of effect in subjects showing a clinical response.

Adult↗

Influence of pulsed electromagnetic field with different pulse duty cycles on neurite outgrowth in PC12 rat pheochromocytoma cells.

The influence of low frequency (50 Hz repetition rate) pulsed electromagnetic field (EMF) on PC12 cell neurite outgrowth in vitro was investigated in this study. We studied the percentage of neurite bearing cells, average length of neurites, and directivity of neurite outgrowth in PC12 cells cultured for 96 h in the presence of nerve growth factor (NGF). PC12 cells were exposed in one incubator to pulsed EMF at 1.36 mT (peak value) generated by a pair of Helmholtz coils, and the control samples were placed in another identical incubator. We found that the pulse duty cycle had significant effect on neurite outgrowth. Low (10%) pulse on-time significantly inhibited the percentage of neurite bearing cells, but at the same time increased the average length of neurites, while 100% on-time (DC) had exactly the opposite effects. Furthermore, we found that neurites were prone to extend along the direction of pulsed EMF with 10% pulse on-time. Our studies show that neurite outgrowth in PC12 cells is sensitive to the pulse duty and this sensitivity was associated with NGF concentration.

Animals↗

Contamination of rivers in Tianjin, China by polycyclic aromatic hydrocarbons.

Tianjin urban/industrial complex is highly polluted by some persistent organic pollutants. In this study, the levels of 16 priority polycyclic aromatic hydrocarbons (PAHs) were tested in sediment, water, and suspended particulate matter (SPM) samples in 10 rivers in Tianjin. The total concentration of 16 PAHs varied from 0.787 to 1943 microg/g dry weight in sediment, from 45.81 to 1272 ng/L in water, and from 0.938 to 64.2 microg/g dry weight in SPM. The levels of PAHs in these media are high in comparison with values reported from other river and marine systems. Variability of total concentrations of PAHs in sediment, water, and SPM from nine different rivers is consistent with each other. No obvious trends of total PAHs concentration variations were found between upstream and downstream sediment, water, and SPM samples for most rivers, which indicate local inputs and disturbances along these rivers. The spatial distributions of three-phase PAHs are very similar to each other, and they are also similar to those found in topsoil. However, their chemical profiles are significantly different from that of topsoil. The change of profiles is consistent with the different aqueous transport capability of 16 PAHs. Low molecular weight PAHs predomination suggests a relatively recent local source and coal combustion source of PAHs in the study area.

China↗

Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus.

We sought to determine which medullary sympathetic premotor neurons mediate the cardiovascular and thermogenic effects resulting from activation of neurons in the dorsomedial hypothalamus (DMH) in urethane/chloralose-anesthetized, artificially ventilated rats. Unilateral disinhibition of neurons in the DMH with microinjection of bicuculline (2 mM, 30 nl) caused significant increases in brown adipose tissue sympathetic nerve activity (BAT SNA, +828+/-169% of control, n=16), cardiac SNA (+516+/-82% of control, n=16), renal SNA (RSNA, +203+/-25% of control, n=28) and, accompanied by increases in BAT temperature (+1.6+/-0.3 degrees C, n=11), end-tidal CO(2) (+0.7+/-0.1%, n=15), heart rate (+113+/-7 beats/min, n=32), arterial pressure (+19+/-2 mm Hg, n=32) and plasma epinephrine and norepinephrine concentrations. Inhibition of neurons in the rostral raphe pallidus (RPa) with microinjection of muscimol (6 mM, 60 nl) abolished the increases in BAT SNA and BAT temperature and reduced the tachycardia induced by disinhibition of DMH neurons. Inhibition of neurons in the RVLM with microinjection of muscimol (6 mM, 60 nl) markedly reduced the increase in RSNA, but did not affect the evoked tachycardia or the increase in arterial pressure. Combined glutamic acid decarboxylase (GAD-67) immunocytochemistry and pseudorabies viral retrograde tracing from BAT indicated close appositions between GABAergic terminals and DMH neurons in sympathetic pathways to BAT. In conclusion, these results demonstrate the existence of a tonically active, GABAergic inhibitory input to neurons in the DMH and that blockade of this inhibition increases sympathetic outflow to thermogenic and cardiovascular targets by activating functionally specific populations of sympathetic premotor neurons: the excitation of BAT SNA and BAT thermogenesis is mediated through putative sympathetic premotor neurons in the RPa, while the activation in RSNA is dependent on those in RVLM. These data increase our understanding of the central pathways mediating changes in sympathetically mediated thermogenesis that is activated in thermoregulation, stress responses and energy balance.

Adipose Tissue, Brown↗

Persistency of adenoviral-mediated lysostaphin expression in goat mammary glands.

Gene therapy has great potential to enable synthesis of protein molecules in targeted cells of an animal. One application may be the production of antibacterial enzymes by the mammary gland as a means of preventing or treating mastitis. We have previously demonstrated that goat mammary cells are capable of producing lysostaphin, an antistaphylococcal enzyme, after being transduced in vivo with a recombinant adenoviral vector containing a modified lysostaphin gene (Ad-lys). The current study examined duration of expression, and antibody response to lysostaphin and the adenoviral vector. Following intramammary infusion into nonlactating goats (n = 4), recovery of transducible adenoviral vector in mammary secretions persisted for 11 d. Transducible vector was not detected in serum, saliva, urine, or feces. Peak lysostaphin concentrations (< 20 microg/mL) in mammary secretions of infused udders were detected approximately 1 wk postinfusion, and generally returned to undetectable levels after an additional 1 to 2 wk. The poor persistency of expression was likely due to the very potent immune response to both the adenovirus and the expressed lysostaphin. Serum IgG antibodies recognizing the adenoviral vector developed within 7 d of the infusion, and titers rose dramatically to greater than 1:1 x 10(5). Similar titers of serum IgG antibodies to lysostaphin developed in 3 goats, with more moderate titers in the fourth goat. The antibody response to lysostaphin was delayed by approximately 4 d in comparison to the response to the adenovirus. Serum IgG antibody profiles were reflected in mammary secretions. No IgA antibodies to adenovirus or lysostaphin were detected in sera or mammary secretion. We demonstrate that while the lysostaphin gene can be introduced to the mammary gland using an adenoviral-mediated gene transfer technique, the strong immune response that it provokes makes the approach unsuitable for combating mastitis.

Adenoviridae↗

Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells.

Latent membrane protein 1 (LMP1), one of the oncoproteins encoded by Epstein-Barr virus is sufficient for the development of nasopharyngeal carcinoma in vivo and nasopharyngeal epithelial cellular immortalization in vitro. It has also been shown to increase the telomerase activity in primary human nasopharyngeal epithelial cells by an unknown mechanism. We reported here that LMP1 could increase telomerase activity in coordination with LMP1-induced c-Myc expression in LMP1-transfected primary human nasopharyngeal epithelial cells or in a dual-stable LMP1 integrated nasopharyngeal carcinoma cell line with Tet-on regulatory system, named Tet-on-LMP1 HNE2 by PCR-ELISA analysis and reporter gene assay. Blocking of LMP1 expression decreased telomerase activity and c-myc transactivation. Mutagenesis of Myc-responsive E-box elements in the minimal core of hTERT promoter could inhibit the hTERT expression induced by LMP1. Moreover, blocking of c-myc transactivation could further decrease LMP1-mediated hTERT expression. It has been suggested that LMP1 can be used to aid myc control telomerase. In addition, we also found that C-terminus of LMP1, including CTAR1 and CTAR2 domains participated in telomerase activation. Together, these findings suggested that LMP1 activated telomerase via c-myc.

Blotting, Western↗

In vivo alteration of the keratin 17 gene in hair follicles by oligonucleotide-directed gene targeting.

Using intradermal injection of a chimeric RNA-DNA oligonucleotide (RDO) or a single-stranded oligonucleotide (ssODN) into murine skin, we attempted to make a dominant mutation (R94p) in the conserve alpha-helical domain of keratin 17 (K17), the same mutation found in pachyononychia congenichia type 2 (PC-2) patients with phenotypes ranging from twisted hair and multiple pilosebaceous cysts. Both K17A-RDO and -ssODN contained a single base mismatch (CGC to CCC) to alter the normal K17 sequence to cause an amino acid substitution (R94P). The complexes consisting of oligonucleotides and cationic liposomes were injected to C57B1/6 murine skin at 2 and 5 day after birth. Histological examination of skin biopsies at postnatal day 8 from several mice showed consistent twisted hair shafts or broken hair follicles at the sebaceous gland level and occasional rupture of the hair bulb or epidermal cyst-like changes. In the injected area, the number of full anagen hair follicles decrease by 50%. Injection of the control oligonucleotide, identical to K17A-RDO but containing no mismatch to the normal sequence, did not result in any detectable abnormality. The frequency of gene alteration was lower than 3%, according to the restriction fragment length polymorphism (RFLP) analysis of the genomic DNA isolated by dissection of hair follicles from slides. Although intradermal injection of K17A-RDO or K17-ssODN caused a dominant mutation in K17 affecting hair growth and morphology, these phenotypic changes were transient either due to the compensation of K17 by other keratins or the replacement of the mutated cells by normal surrounding cells during hair growth.

Animals↗

Metallic inductive and capacitive grids: theory and experiment.

We present theoretical modeling and experimental validation of both capacitive (dot) and inductive (hole) metallic crossed gratings in the mid-infrared (2-5 microm). The gratings are fabricated by use of interferometric lithography and modeled by use of rigorous coupled-wave analysis. Our experimental and numerical investigations of the transmittance spectra of these gratings suggest that, as in inductive grids, the behavior of capacitive grids is described by the coupling of the incident light into surface plasma waves.

Journal Article↗

Adenoviral-mediated transfer of a lysostaphin gene into the goat mammary gland.

As a step toward preventing and curing Staphylococcus aureus mastitis, an adenoviral-mediated gene transfer technique was used to enable mammary cells to synthesize and secrete lysostaphin, an anti-staphylococcal protein. A lysostaphin gene, modified for eukaryotic expression of the bioactive variant, Gln125,232-lysostaphin, was inserted into a replication deficient adenovirus by homologous recombination in 293 cells. The resulting adenoviral vector containing the modified lysostaphin gene (Ad-lys) was used to infect bovine mammary epithelial cells in vitro and caprine mammary cells in vivo. A similar adenoviral vector containing the Escherichia coli gene encoding beta-galactosidase (Ad-lacZ) was also evaluated. Transduction of cultured bovine cells by Ad-lacZ was confirmed by the presence of beta-galactosidase in fixed cells 48 h postinfection. Bovine cells transduced by Ad-lys secreted immunoreactive Gln125,232-lysostaphin (0.8 microg/ml) into media that had approximately 20% bioactivity compared with native lysostaphin. To evaluate transduction in vivo, udder halves of four nonlactating goats were exposed to 10(10) plaque-forming units (pfu) ofAd-lacZ by two intramammary infusions given 48 h apart. The animals were euthanized 24 h later, and extensive expression of beta-galactosidase was detected in cells lining the teat canals, with more moderate expression observed in adjoining mammary parenchyma. Udder halves of two other nonlactating goats were infused with 10(10) pfu of Ad-lys while contralateral udder halves received Ad-lacZ. The animals were euthanized 48 h postinfusion. In both animals, extensive expression of beta-galactosidase was detected in Ad-lacZ exposed teats. Immunoreative Gln125,232-lysostaphin was detectable in secretions from Ad-lys exposed glands 24 h postinfusion, increasing to approximately 1 microg/ml at 48 h postinfusion. As with cultured bovine mammary epithelial cells, the bioactivity of goat-derived Gln125,232-lysostaphin was approximately 20% of native lysostaphin. These results demonstrate that an adenoviral vector can be used to introduce a gene into the ruminant mammary gland, enabling the secretion of a bioactive form of lysostaphin.

Adenoviridae↗

Alternating stereospecific copolymerization of ethylene and propylene with metallocene catalysts.

The copolymerization of ethylene and propylene with bridged metallocenes Me(2)E(3-RCp)(Flu)X(2)/MAO (E = C, X = Me; E = Si, X = Cl; R = H or alkyl) was investigated. Ethylene/propylene copolymerization with metallocenes having heterotopic active sites (R =Me, i-Pr) yield alternating, isotactic ethylene/propylene copolymers with percentages of alternating EPE+PEP triads in the range of 61-76% at 50% ethylene incorporation. Both the nature of the substituent R and the bridge E influence the copolymerization behavior including the copolymerization activity, copolymer sequence distribution, molecular weight, and stereochemistry. Silicon-bridged metallocenes produce copolymers with higher activity and molecular weight but lower propylene incorporation at similar feeds than the carbon-bridged analogues. Isotactic PEPEP sequences were observed for all metallocenes, while the tacticities of the EPPE sequences varied with the bridge and the substituent on the metallocene ligand. Isotactic PEPEP sequences and atactic EPPE sequence errors in the alternating copolymers are consistent with a mechanism where the comonomers are enchained alternately at the heterotopic coordination sites of the metallocenes. Isotactic EPPE sequences are indicative of occasional multiple insertions at the stereospecific site, caused by an isomerization of the chain prior to monomer insertion (backskip).

Journal Article↗

Involvement of the MAP kinase pathways in induction of GADD45 following UV radiation.

The p53-regulated stress-inducible gene GADD45 has been shown to participate in cellular response to DNA damage, including cell cycle checkpoint, apoptosis, and DNA repair. However, the regulation of GADD45 expression is complex and may involve both p53-dependent and -independent pathways. Recent findings have demonstrated that the p53-independent induction of GADD45 is mainly regulated by the transcription factors Oct-1 and NF-YA, which directly bind to their consensus motifs located at the GADD45 promoter region. Here, we report that mitogen-activated protein (MAP) kinases are involved in the induction of the GADD45 promoter after DNA damage. Inhibition of JNK1 and ERK kinase activities either by expression of the dominant negative mutant JNK1 or by treatment with a selective chemical inhibitor of ERK (PD098059) substantially abrogates the UV induction of the GADD45 promoter. In contrast, a p38 kinase inhibitor (SB203580) has little effect on GADD45 induction by UV. In addition, the GADD45 promoter is strongly activated following expression of JNK1; Raf-1, which is an upstream activator of the ERK pathway; or MEK1, an upstream activator of both the ERK and the JNK pathways. Activation of the GADD45 promoter by MAP kinases does not require normal p53 function. Interestingly, the MAP kinase-regulatory effect appears to be mediated via OCT-1 and CAAT motifs since disruption of these sites abrogates activation of the GADD45 promoter by MAP kinases. Therefore, these findings indicate that the MAP kinase pathways are involved in the regulation of the p53-independent induction of the GADD45 promoter, probably via interaction with transcription factors that directly bind to OCT-1 and CAAT motifs.

Amino Acid Motifs↗

Transcription factors Oct-1 and NF-YA regulate the p53-independent induction of the GADD45 following DNA damage.

The p53-regulated GADD45 gene is one of the important players in cellular response to DNA damage, and probably involved in the control of cell cycle checkpoint, apoptosis and DNA repair. There are both the p53-dependent and -independent pathways that regulate GADD45 induction. Following ionizing radiation, induction of the GADD45 gene is regulated by p53 through the p53-binding motif located in the third intron of the GADD45 gene. In contrast, GADD45 induction by methyl methanesulfonate (MMS), UV radiation (UV), and medium starvation is independent of p53 status although p53 may contribute to these responses. However, the regulatory elements that control the p53-independent induction of GADD45 remain uncertain. In this report, we have performed detailed analyses to characterize the responsive components that are required for the induction of the GADD45 promoter. We have found that the region between -107 and -62 of the GADD45 promoter is crucial for the induction. Sequence analysis indicates that there are two OCT-1 sites and one CAAT box located in this region. Site-directed mutations of both OCT-1 and CAAT motifs substantially abrogate the induction of the GADD45 promoter by DNA damage. In addition, both Oct-1 protein (binding to OCT-1 site) and NF-YA protein (binding to CAAT box) are induced after cell exposure to DNA damaging agents. Moreover, the Electrophoretic Mobility Shift Assay (EMSA) has demonstrated the direct bindings of Oct-1 and NF-YA proteins to their consensus sequences in the GADD45 promoter. Therefore, these results have presented the novel observation that transcription factors Oct-1 and NF-YA participate in the cellular response to DNA damage and are involved in the regulation of stress-inducible genes.

Base Sequence↗

Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and promotes cellular survival.

Cellular proliferation and survival are modulated by the expression of specific genes. Cytokine response gene 8 (CR8), which was originally cloned as an IL-2-induced gene in human T lymphocytes, encodes a basic helix--loop--helix (bHLH) transcription factor. The CR8 gene product is highly conserved among human, mouse and rat, and contains sequence motifs that distinguish it from other bHLH families. The CR8 gene is ubiquitously expressed, and CR8 gene expression is induced by both growth-promoting as well as growth-inhibitory stimuli. As bHLH proteins have been found to regulate both the G1-S phase cell cycle transition, as well as cellular survival, the effects of CR8 on these processes were investigated. Ectopic CR8 expression in asynchronous U2OS cell cultures reduces the percentage of cells in the cell cycle S phase, and also slows the entry of G1-synchronized cells into S phase. The prolonged G1 interval correlates with impaired elevation of cyclin E protein and prolonged p21 protein expression in G1. CR8 expression also protects U2OS cells from serum-withdrawal induced apoptosis. These results indicate that CR8 is an important modulator of both the G1-S phase cell cycle transition, and cellular survival.

Amino Acid Sequence↗

Regulation of systemic acquired resistance by NPR1 and its partners.

The NPR1 protein of Arabidopsis thaliana has been shown to be an important regulatory component of systemic acquired resistance (SAR). Mutations in the NPR1 gene block the induction of SAR by the signal molecule salicylic acid (SA). NPR1 contains an ankyrin repeats and a BTB domain which are involved in interaction with other protein(s). To further study the function of NPR1 and the regulatory mechanism of SAR, we used both molecular and genetic approaches to identify additional SAR regulatory components. Through a yeast two-hybrid screen we found that NPR1 interacts specifically with bZIP transcription factors. The involvement of bZIP transcription factors in controlling the SA-induced genes had been suggested by a number of promoter studies performed on these genes. It was found that as1 element, which is a binding site for bZIP transcription factors, is essential for SA-induced gene expression. In a genetic screen for suppressors of npr1, we found a mutant, sni1, that restored the responsiveness to SAR induction in npr1. The genetic characteristics of the sni1 mutant and the sequence of SNI1 suggest that the wild-type SNI1 protein is a negative regulator of SAR. We believe that SAR is controlled by both positive regulators and negative regulators.

Arabidopsis↗

The relationship of oxidative DNA damage marker 8-hydroxydeoxyguanosine and glycoxidative damage marker pentosidine.

OBJECTIVES: 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage. Pentosidine is a biomarker of glycoxidation reaction. In this study, we investigated relationships among 8-OHdG, pentosidine and age. DESIGN AND METHODS: We determined the urinary concentrations of 8-OHdG and pentosidine in adults with mild hypercholesterolemia or/and mild hypertension (hypercholesterolemia group, n = 31; hypertension group, n = 25; hypercholesterolemia and hypertension group, n = 7). RESULTS: The strength of the relationship between 8-OHdG and age was the same as that between pentosidine and age (the correlation coefficient between 8-OHdG and age was 0.33, pentosidine and age was 0.37). In addition, there was a positive and significant correlation between 8-OHdG and pentosidine. On the other hand, mean values of 8-OHdG and pentosidine showed no significant difference among the three groups. CONCLUSION: The results of the present study indicate that both 8-OHdG and pentosidine levels increase similarly in degenerative pathologic conditions.

8-Hydroxy-2'-Deoxyguanosine↗