Forest-associated habitat variables influence human-tick encounters in the southeastern United States.

Due to the increased frequency of human-tick encounters and expanding ranges of ticks in the United States, there is a critical need to identify environmental conditions associated with tick populations and their likelihood to contact human hosts. In a passive tick surveillance partnership with the US Department of Agriculture Forest Inventory and Analysis (FIA) program, we identified environmental variables associated with tick encounters by forestry personnel. Ticks were identified by species and life stage, and site-specific variables were associated with each tick using FIA forest inventory datasets and generalized linear models with negative binomial distributions. Of the 55 FIA variables available, we identified biotic and abiotic environmental variables associated with Amblyomma americanum L. (carbon in litter material and standing dead tree aboveground dry biomass), Dermacentor variabilis Say (seedling species unevenness and elevation), and Ixodes scapularis L. (carbon in dead woody material and seedling species unevenness). We propose conducting future treatment-control studies using these forestry-related environmental variables to test their ability to alter tick abundance at sites. Land management decisions not only affect common flora and fauna, but changes to these habitats can also alter the way ticks parasitize hosts and use vegetation to find those hosts. These results can be used with land management decisions to prevent future human-tick encounters and highlight risk areas.

A Unique Academic-Government Collaboration Yields First Report of Detailed Habitat Description for Haemaphysalis longicornis (Ixodida: Ixodidae) in Madison County, KY.

Haemaphysalis longicornis Neumann, Asian longhorned tick, was collected in Madison County, Kentucky, United States as part of an ongoing collaborative-tick surveillance project. This is the first collection of this invasive tick that includes ancillary data on habitat and landscape features derived from the USDA Forest Service, Forest Inventory and Analysis program.

Multichannel deconvolution of vibrational signals: A state-space inverse filtering approach.

Deconvolution of noisy measurements, especially when they are multichannel, has always been a challenging problem. The processing techniques developed range from simple Fourier methods to more sophisticated model-based parametric methodologies based on the underlying acoustics of the problem at hand. Methods relying on multichannel mean-squared error processors (Wiener filters) have evolved over long periods from the seminal efforts in seismic processing. However, when more is known about the acoustics, then model-based state-space techniques incorporating the underlying process physics can improve the processing significantly. The problems of interest are the vibrational response of tightly coupled acoustic test objects excited by an out-of-the-ordinary transient, potentially impairing their operational performance. Employing a multiple input/multiple output structural model of the test objects under investigation enables the development of an inverse filter by applying subspace identification techniques during initial calibration measurements. Feasibility applications based on a mass transport experiment and test object calibration test demonstrate the ability of the processor to extract the excitations successfully.

No Evidence of Competition Between the Blacklegged Tick (Acari: Ixodidae) and American Dog Tick on the Rodent Host White-Footed Deermouse (Rodentia: Cricetidae) in Southwestern Tennessee.

Investigations that analyze interspecific associations of vectors on their hosts are important for understanding community structure and implementing ways to comprehend mechanisms of pathogen transmission. We assessed the interspecific association of two tick species (Ixodes scapularis Say (Ixodida: Ixodidae) and Dermacentor variabilis Say (Ixodida: Ixodidae)) on the rodent host Peromyscus leucopus Rafinesque (Rodentia: Cricetidae) at the Hobart Ames Research and Education Center in southwestern Tennessee. Of the rodents captured, 95 (63%) had neither species of tick, 6 (4%) had both tick species, 25 (16%) had I. scapularis only, and 26 (17%) had D. variabilis only. A coefficient of association (C7 = -0.08) was calculated, which suggested there was competition between the two species of ectoparasites, but this value was not significant, indicating that there was a neutral relationship between the tick species on P. leucopus. The co-occurrence of both tick species on their host at the same time suggested that the two tick species can occupy the same host and use the same resources without competing.

Spatial-temporal clusters of host-seeking Aedes albopictus, Aedes japonicus, and Aedes triseriatus collections in a La Crosse virus endemic county (Knox County, Tennessee, USA).

A bite from a La Crosse virus (LACV) infected Aedes mosquito can cause La Crosse encephalitis (LACE), which is a neuro-invasive disease that disproportionately affects children under the age of 16 in Southern Appalachia. The three vectors for LACV are Aedes albopictus (Skuse), Ae. japonicus (Theobald), and Ae. triseriatus (Say). Localized maps of the geographic distribution of vectors are practical tools for mosquito management personnel to target areas with high mosquito abundance. This study hypothesized that LACV vectors have unique species-specific spatial and temporal clusters. To test this, 44 sites were identified in Knox County, Tennessee for their land use/type. At each site, host-seeking mosquitoes were collected approximately every other week from May-October 2018. Spatial clusters of host-seeking mosquito collections for each of the three mosquito species were investigated using Kulldorff's spatial scan statistic, specifying a retrospective space-time Bernoulli model. Most vector clusters were identified in south-central Knox County while the seasonality of clusters varied by mosquito species. Clusters of Ae. albopictus were observed throughout the entire study period while clusters of Ae. japonicus and Ae. triseriatus only occurred May-June. The findings indicate that the relative abundance of LACV vectors were more abundant in south-central Knox County compared to the rest of the county. Of interest, these clusters spatially overlapped with previous LACE diagnosed cases. These findings are useful in guiding decisions on targeted mosquito control in Knox County and may be applied to other counties within Southern Appalachia.

Small-mammal characteristics affect tick communities in southwestern Tennessee (USA).

Life histories can influence the degree of parasite infestations on a host. Pressures exerted on hosts based on age and sex convey varying degrees of parasite prevalence due to differences in host lifestyles, but it is not known how interactions between different host traits affect tick numbers. The objective of this study was to determine if host characteristics (e.g., age, sex, weight, and their interactions) affect the mean number of ticks found on small mammals regardless of host species or habitat. Sherman live traps were placed in forest and grass/forb habitats representative of the southeastern United States. After capture, host characteristics were recorded, and hosts were then searched for ticks. A total of 281 small mammals (148 Peromyscus leucopus, 34 P. maniculatus, 76 Sigmodon hispidus, 16 Microtus pinetorum, and 7 Ochrotomys nuttalli) and 610 ticks (488 Dermacentor variabilis, 114 Ixodes scapularis, 1 Amblyomma americanum, and 7 A. maculatum) were collected in this study. Host's age, sex, and weight affected the number of ticks collected from small mammals and significant interaction effects between host traits occurred (weight by sex, weight by age, and sex by age). For instance, female subadult rodents had significantly more ticks compared to female adults, male subadults had significantly fewer ticks compared to male adults, and the number of ticks on a host increased as host body mass increased. These results support the hypothesis that the number of ticks vary on rodent hosts based on life histories and trait interactions. Therefore, understanding the behavioral mechanisms of a host can aid in the management of parasites in the environment.

La Crosse Virus Vectors Are Host-Seeking and Ovipositing After 1700 H in Eastern Tennessee.

La Crosse virus (LACV) is transmitted via the bites of infected Aedes mosquitoes (Ae. triseriatus, Ae. albopictus, and Ae. japonicus) and causes La Crosse encephalitis, which is the most commonly diagnosed arbovirus in eastern Tennessee children. This study identified host-seeking and oviposition activity of LACV vectors over a diel period, as it relates to traditional working hours. Nineteen sites in Knox County, TN, were monitored with host-seeking (Centers for Disease Control and Prevention [CDC] miniature light traps) and oviposition traps (CDC gravid traps) during 2 diel periods (0900-1700 h and 1700-900 h). We collected 2,444 adult mosquitoes, comprising 19 different species of which 1,337 (54.7%) were LACV vectors: Ae. albopictus (1,207 specimens), Ae. triseriatus (85 specimens), and Ae. japonicus (45 specimens). These species were active throughout the sampling period, but significantly more were collected from 1700-0900 h. The CDC gravid trap was the most effective method for monitoring Ae. japonicus; there were no trap effects or trap × time interactive effects for Ae. albopictus or Ae. triseriatus. Overall, significantly more LACV vectors were collected from 1700-0900 h compared to 0900-1700 h. Information gathered in this study improves vector surveillance, helps communities control mosquito populations, and minimizes nontarget effects.

Evaluating Surveillance Methods for Arboviral Vectors of La Crosse Virus and West Nile Virus of Southern Appalachia.

To monitor mosquito-borne diseases, public health departments conduct mosquito and pathogen surveillance. Our objective was to evaluate mosquito monitoring methods for collecting La Crosse virus (LACV) and West Nile virus (WNV) vectors (Aedes and Culex mosquitoes, respectively) in southern Appalachia. Centers for Disease Control and Prevention (CDC) light traps baited with carbon dioxide (CO(2)), CDC light traps baited with CO(2) and BG lure, BG-Sentinel traps baited with CO(2), gravid traps baited with oak (Quercus)-water infusion, and resting traps were compared in eastern Tennessee in 2013. Traps operated at 8 different urban sites throughout Knox County were randomly assigned to and rotated among 6 plots within each site. Results were specific for each vector; the BG-Sentinel trap was the best method for Aedes triseriatus, the CDC trap baited with CO(2) and BG lure was the best method for Ae. albopictus, and the gravid trap was the best method for Ae. japonicus. Culex erraticus collections varied by week and trapping method, indicating no single method was best, but the questing traps collected more mosquitoes. There was no significant trapping difference for Cx. pipiens complex in this region using the methods tested. The results suggest using a combination of trapping methods when sampling for LACV and/or WNV mosquito vectors in southern Appalachia. Effective trapping methods are necessary to enable accurate surveillance, improve control methods, enhance understanding of dispersal, and use for early detection of vectors and pathogens.

Incomplete lung recovery following sub-acute inhalation of combustion-derived ultrafine particles in mice.

BACKGROUND: Particulate matter (PM) is one of the six criteria pollutant classes for which National Ambient Air Quality Standards have been set by the United States Environmental Protection Agency. Exposures to PM have been correlated with increased cardio-pulmonary morbidity and mortality. Butadiene soot (BDS), generated from the incomplete combustion of 1,3-butadiene (BD), is both a model PM mixture and a real-life example of a petrochemical product of incomplete combustion. There are numerous events, including wildfires, accidents at refineries and tank car explosions that result in sub-acute exposure to high levels of airborne particles, with the people exposed facing serious health problems. These real-life events highlight the need to investigate the health effects induced by short-term exposure to elevated levels of PM, as well as to assess whether, and if so, how well these adverse effects are resolved over time. In the present study, we investigated the extent of recovery of mouse lungs 10 days after inhalation exposures to environmentally-relevant levels of BDS aerosols had ended. METHODS: Female BALB/c mice exposed to either HEPA-filtered air or to BDS (5 mg/m(3) in HEPA filtered air, 4 h/day, 21 consecutive days) were sacrificed immediately, or 10 days after the final BDS exposure. Bronchoalveolar lavage fluid (BALF) was collected for cytology and cytokine analysis. Lung proteins and RNA were extracted for protein and gene expression analysis. Lung histopathology evaluation also was performed. RESULTS: Sub-acute exposures of mice to hydrocarbon-rich ultrafine particles induced: (1) BALF neutrophil elevation; (2) lung mucosal inflammation, and (3) increased BALF IL-1ß concentration; with all three outcomes returning to baseline levels 10 days post-exposure. In contrast, (4) lung connective tissue inflammation persisted 10 days post-exposure; (5) we detected time-dependent up-regulation of biotransformation and oxidative stress genes, with incomplete return to baseline levels; and (6) we observed persistent particle alveolar load following 10 days of recovery. CONCLUSION: These data show that 10 days after a 21-day exposure to 5 mg/m(3) of BDS has ended, incomplete lung recovery promotes a pro-biotransformation, pro-oxidant, and pro-inflammatory milieu, which may be a starting point for potential long-term cardio-pulmonary effects.

Survey of Ticks Collected from Tennessee Cattle and Their Pastures for Anaplasma and Ehrlichia Species.

Anaplasma marginale is the causative agent for bovine anaplasmosis (BA) and Ehrlichia ruminantium is the causative agent for heartwater, 2 devastating diseases of cattle. BA is common in the United States and frequently reported in western Tennessee cattle; however, cases of heartwater are not yet established in the continental United States. Because both pathogens are transmitted via the bites of infected ticks, the objective of this study was to survey cattle and pastures for ticks and for each pathogen. University of Tennessee AgResearch has 7 research and education centers (REC) located throughout the state at which they manage cattle. Ticks were collected from selected cattle (every fourth to sixth animal) and pastures (via dragging) associated with the herd from each REC during the summer of 2013. A total of 512 ticks were collected from cattle (n = 386) and pastures (n = 126) and were PCR-screened for Anaplasma and Ehrlichia using genus-specific primers. Collections consisted of 398 (77.7%) Amblyomma americanum, 84 (16.4%) Amblyomma maculatum, and 30 (5.9%) Dermacentor variabilis. Ticks were not recovered from pastures or cattle east of the Tennessee Plateau. The North American vectors for An. marginale and E. ruminantium were identified (D. variabilis and A. maculatum, respectively), but neither pathogen was recovered. A large proportion of ticks were collected from cattle and, of these, a majority were attached to their host (compared to questing on their host or engorged on the host). Four A. americanum were positive for Ehrlichia spp. (Ehrlichia ewingii, Ehrlichia chaffeensis, and Panola Mountain Ehrlichia), all in western Tennessee. With the identification of a few Ehrlichia infections in cattle-associated ticks and current A. marginale rates in Tennessee beef cattle nearing 11%, additional research is needed to establish baseline tick, Anaplasma, and Ehrlichia data for future management studies.

A bovine herpesvirus type 1 mutant virus with truncated glycoprotein E cytoplasmic tail has defective anterograde neuronal transport in rabbit dorsal root ganglia primary neuronal cultures in a microfluidic chamber system.

Bovine herpesvirus type 1 (BHV-1) is an important component of the bovine respiratory disease complex (BRDC) in cattle. Following primary intranasal and ocular infection of cattle, BHV-1 establishes lifelong latent infection in trigeminal ganglia (TG). Upon reactivation from latency, the virus is transported from neuronal cell bodies in the TG to projected nerve endings in nose and cornea of latently infected cattle where the virus shedding occurs. This property of BHV-1 plays a significant role in the pathogenesis of BRDC and maintenance of BHV-1 in the cattle population. Recently, we have reported that a glycoprotein E (gE) cytoplasmic tail-truncated BHV-1 (BHV-1 gEAm453) did not reactivate from latency and was not shed in the nasal and ocular secretions of calves and rabbits. Here we describe the methods to establish rabbit primary dorsal root ganglia (DRG) neuron cultures in a microfluidic chamber system and to characterize in vitro anterograde and retrograde axonal transport properties of BHV-1 gE-deleted and BHV-1 cytoplasmic tail-truncated gEAm453 mutant viruses relative to BHV-1 gEAm453-rescued/wild-type viruses. The results clearly demonstrated that whereas the BHV-1 gE-deleted, BHV-1 gEAm453, and BHV-1 gEAm453-rescued/wild-type viruses were transported equally efficiently in the retrograde direction, only the BHV-1 gEAm453-rescued/wild-type virus was transported anterogradely. Therefore, we have concluded that sequences within the BHV-1 gE cytoplasmic tail are essential for anterograde axonal transport and that primary rabbit DRG neuronal cultures in the microfluidic chambers are suitable for BHV-1 neuronal transport studies.

Modulation of K65R selection by zidovudine inclusion: analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (study COL40263).

COL40263 was a pilot 48-week, open-label, multicenter study evaluating the efficacy and safety of once-daily coformulated abacavir/lamivudine/zidovudine plus tenofovir in ART-naive, HIV-infected subjects. We examined the patterns of resistance that were selected on-therapy through 48 weeks in subjects with virologic nonresponse (VF). A total of 123 antiretroviral-naive HIV-1-infected subjects with plasma HIV-1 RNA > or = 30,000copies/ml were enrolled. For subjects with confirmed VF (HIV-1 RNA > or = 400 copies/ml at week 24 or later), HIV population genotypic and phenotypic analysis was performed. Of the 123 enrolled subjects, 14 (11%) had confirmed plasma HIV-1 RNA > or = 400 copies/ml through week 48. Of these subjects, 3/14 had evidence of drug resistance at baseline: 2/14 had HIV with K103N, Y188F/H/L/Y, and/or T215A and 1/14 had reduced zidovudine susceptibility. At the last time point analyzed, 4/14 subjects had wild-type HIV, while 10/14 subjects had HIV with either thymidine analogue mutations (TAMS) alone (3/10), TAMS + M184V (4/10), M184V only (1/10), or K65R/K (2/10). Matched phenotype was obtained for 13/14 subjects and 8/13 (62%) subjects had reduced susceptibility to one or more study drugs: 2/13 tenofovir, 3/13 abacavir, 4/13 zidovudine, and 7/13 lamivudine. The resistance pattern in COL40263 subjects with VF differs significantly from that reported for tenofovir-containing triple-nucleoside regimens. TAMs were detected in the majority (7/10) of samples from subjects with VF who selected any resistance mutation. These data suggest that TAMs selection is a preferred resistance route of this combination, with zidovudine modulating the resistance pathway against selection for K65R.

Development and optimisation of a procedure for the production of Parapoxvirus ovis by large-scale microcarrier cell culture in a non-animal, non-human and non-plant-derived medium.

For the production of a chemically inactivated Parapoxvirus ovis (PPVO), an adherent bovine kidney cell line was cultivated on Cytodex-3 microcarriers in suspension culture. The inactivated and purified virus particles have shown immune modulatory activity in several animal models. PPVO was produced by a biphasic batch process at the 3.5 and 10 L scale. Aeration was realised by bubble-free membrane oxygenation via a tube stator with a central two-blade anchor impeller. In order to increase efficiency, process robustness and safety, the established process was optimised. The cell line was adapted to a protein-free medium (except recombinant insulin) in order to increase biosafety. A scale up to a 50 L pilot plant with direct cell expansion was performed successfully. In parallel, the biphasic batch process was optimised with special emphasis on different operating conditions (cell number, Multiplicity of Infection (MOI), etc.) and process management (fed-batch, dialysis, etc.). The quality and concentration of the purified virus particles was assessed by quantitative electron microscopy, residual host cell protein and DNA-content and, finally, biologic activity in a transgenic mouse model. This integrated approach led to a new, safe, robust and highly productive large-scale production process, called "Volume-Expanded-Fed" Batch with cell densities up to 6-7e06 cells/mL. By subsequent dilution of infected cells into the next process scale, an increase in total productivity by a factor of 40 (related to an established biphasic batch process) was achieved.

Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma invasion.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Although modern therapy has produced five-year survival rates as high as 70% for some MB patients, this resulted in significant long-term treatment-related morbidity. The cellular mechanisms involved in metastatic spread of medulloblastoma are largely unknown. Neurotrophins (NT) comprise a family of structurally and functionally related neurotrophic factors that are critical for central nervous system (CNS) development with nerve growth factor (NGF) being the prototypic NT. NT acts through two groups of structurally unrelated neurotrophin receptors (NTR): a family of receptor tyrosine kinases (Trks, mainly TrkA, TrkB, and TrkC) and a tumor necrosis factor receptor (TNFR)-like molecule called p75NTR TrkC expression is a good prognostic indicator for MB. TrkC binds only to neurotrophin-3 (NT-3) whereas p75 binds to all NT family members. Importantly, little is known about the biological functions of p75 in primitive neuroectodermal tumors such as MB. In contrast, NT-regulated heparanase (HPSE) is a unique extracellular matrix-degrading enzyme known to be associated with tumor progression in a wide variety of cancers. However, HPSE roles in MB invasive pathways have not been investigated. We provide evidence of a differential expression of HPSE in newly-developed medulloblastoma cell lines. Secondly, we show a correlation between HPSE expression and the invasive properties of these medulloblastoma lines. Thirdly, by performing investigations to elucidate prognostic implications of HPSE and TrkC/p75NTR expression in MB, we demonstrate a correlation between p75NTR and HPSE expression. Finally, by using antibodies specific to TrkC and immunohistochemistry (IHC) we prove that IHC scores reveal a significant expression of HPSE in 76% of MB tissues from children aged 3 years and older. Taken together, our data provide evidence that HPSE functionality, in a context linked to TrkC and p75NTR activation, may play critical roles in medulloblastoma tumor invasion and progression.

Dihydroxythiophenes are novel potent inhibitors of human immunodeficiency virus integrase with a diketo acid-like pharmacophore.

We have identified dihydroxythiophenes (DHT) as a novel series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors with broad antiviral activities against different HIV isolates in vitro. DHT were discovered in a biochemical integrase high-throughput screen searching for inhibitors of the strand transfer reaction of HIV-1 integrase. DHT are selective inhibitors of integrase that do not interfere with virus entry, as shown by the inhibition of a vesicular stomatitis virus G-pseudotyped retroviral system. Moreover, in quantitative real-time PCR experiments, no effect on the synthesis of viral cDNA could be detected but rather an increase in the accumulation of 2-long-terminal-repeat cycles was detected. This suggests that the integration of viral cDNA is blocked. Molecular modeling and the structure activity relationship of DHT demonstrate that our compound fits into a two-metal-binding motif that has been suggested as the essential pharmacophore for diketo acid (DKA)-like strand transfer inhibitors (Grobler et al., Proc. Natl. Acad. Sci. USA 99:6661-6666, 2002.). This notion is supported by the profiling of DHT on retroviral vectors carrying published resistance mutations for DKA-like inhibitors where DHT showed partial cross-resistance. This suggests that DHT bind to a common site in the catalytic center of integrase, albeit with an altered binding mode. Taken together, our findings indicate that DHT are novel selective strand transfer inhibitors of integrase with a pharmacophore homologous to DKA-like inhibitors.

Secondary organic aerosols from anthropogenic and biogenic precursors.

Secondary organic aerosol (SOA) formation from the photooxidation of an anthropogenic (1,3,5-trimethylbenzene) and a biogenic (alpha-pinene) precursor was investigated at the new PSI smog chamber. The chemistry of the gas phase was followed by proton transfer reaction mass spectrometry, while the aerosol chemistry was investigated with aerosol mass spectrometry, ion chromatography, laser desorption ionization mass spectrometry, and infrared spectroscopy, along with volatility and hygroscopicity studies. Evidence for oligomer formation for SOA from both precursors was given by an increasing abundance of compounds with a high molecular weight (up to 1000 Da) and by an increasing thermal stability with increasing aging time. The results were compared to data obtained from ambient aerosol samples, revealing a number of similar features.

Identification of organic acids in secondary organic aerosol and the corresponding gas phase from chamber experiments.

Organic acids in the gas and aerosol phase from photooxidation of 1,3,5-trimethylbenzene in the presence of 300 ppb propene and 300 ppb NOx in smog chamber experiments were determined using a wet effluent diffusion denuder/aerosol collector coupled to ion chromatography (IC) with conductivity detection. Behind the IC, the samples were collected using a fraction collector, for identification of unresolved/unidentified organic acids with IC-mass spectrometry (MS). In total, 20 organic acids were found with MS of which 10 were identified. The organic acids identified offline by IC-MS were then further quantified based on the online IC data. The identification was additionally confirmed with gas chromatography-mass spectrometry. At the maximum aerosol concentration, organic acids comprised 20-45% of the total aerosol mass. The method has a detection limit of 10-100 ng/m3 for the identified carboxylic acids.

Identification of polymers as major components of atmospheric organic aerosols.

Results from photooxidation of aromatic compounds in a reaction chamber show that a substantial fraction of the organic aerosol mass is composed of polymers. This polymerization results from reactions of carbonyls and their hydrates. After aging for more than 20 hours, about 50% of the particle mass consists of polymers with a molecular mass up to 1000 daltons. This results in a lower volatility of this secondary organic aerosol and a higher aerosol yield than a model using vapor pressures of individual organic species would predict.

Morte celular nas lâminas epidermais de equinos com laminite

O artigo não apresenta resumo.

Articular chondrocyte apoptosis in equine osteoarthritis.

Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte apoptosis has been implicated as a major pathological OA change in humans and experimental animals but no studies have been performed on equine OA. Articular cartilage was collected from three normal and five OA horses. Histopathological changes were scored by a modified Mankin grading system. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from chondrocytes was indirectly evaluated by immunohistochemistry with polyclonal antibody to nitrotyrosine. The histopathological score and percentage of chondrocyte apoptosis from the OA cartilages were significantly higher than from normal cartilages. There was a significant correlation between histopathological grade and the percentage of chondrocyte apoptosis. OA cartilages exhibited stronger immunoreactivity to nitrotyrosine than normal cartilage. Topographical distributions of chondrocyte apoptosis, cartilage matrix degeneration, and NO production overlapped in equine OA cartilages, suggesting that these pathological phenomena are closely interrelated.