Normal Electrocardiographic Pattern in Conscious Healthy Domestic Geese (Anser anser).

The aim of this study was to describe the reference intervals of electrocardiographic patterns and values in conscious healthy domestic geese (Anser anser). Standard bipolar and augmented unipolar limb lead electrocardiograms with a direct writing electrocardiograph were recorded in 14 domestic geese. The durations of PR interval, QRS complex, ST and QT intervals, the net of the QRS complex, and the P and T amplitudes were determined at 50 mm/s and at 1 cm = 1 mV. The polarity waveform was examined. The mean electrical axis in the frontal plane was determined in leads II and III. Data are expressed as means and standard deviations. The mean (SD) heart rate was 153.8 (22.4) beats/min. The QRS complex was mainly negative in leads II and III; it was positive in the augmented vector right, augmented vector left, and augmented vector foot leads. The T wave was positive in leads II, III, and the augmented vector foot lead and was negative in the augmented vector right and left leads. The mean electrical axis ranged between -30° to -140°. Electrocardiogram recordings were well tolerated by the geese. The reference intervals provided here can be used to assist in the interpretation of electrocardiographic patterns in geese.

Use of contrast-enhanced ultrasound for assessment of nodular lymphoid hyperplasia (NLH) in canine spleen.

BACKGROUND: Nodular lymphoid hyperplasia (NLH) is one of the most common non-neoplastic splenic lesions in dogs, especially in old ones, showing a splenic enlargement. More recent studies have been focused on Contrast Enhanced Ultrasonography (CEUS) analysis of the spleen for establishing normal perfusion patterns and blood pool phase peculiarities of focal lesions. The aim of the study was to evaluate the qualitative and quantitative CEUS analysis of the canine splenic NLH, characterizing the CEUS pattern of this pathology on 20 clinical cases. RESULTS: A prospective, observational study was performed using a system equipped with contrast-tuned imaging technology. Mechanical Index was set from 0.08 to 0.11; the contrast medium was a second generation contrast medium composed of sulphur hexafluoride encapsulated of a shell of phospholipids (SonoVue®). Qualitative and quantitative assessment of the enhancement pattern of splenic NLH were performed. Cytology and histology identified 20 splenic NLH. All of the benign hyperplastic lesions assessed were isoechoic with a homogeneous pattern than the surrounding normal spleen, during the wash-in phase (10-20 s) of the CEUS exam. Before finishing the wash-in phase, 20-45 s from the contrast medium inoculation, 19/20 benign nodules became markedly hypoechoic to the adjacent spleen. Sensitivity of hypoechoic pattern for NLH was 95%. CONCLUSIONS: These findings should prove useful in the evaluation of focal splenic masses in dogs. Since enhancement and perfusion patterns of NLH seem to coincide with some neoplastic lesions of the spleen previously reported, in clinical practice attention must be paid to the final diagnosis of canine splenic lesions using only the CEUS exam.

Quantitative evaluation of canine urinary bladder transitional cell carcinoma using contrast-enhanced ultrasonography.

BACKGROUND: In veterinary medicine, contrast-enhanced ultrasonography allowed the accurate quantification of liver, splenic and kidney vascularization in healthy dogs and the differentiation between malignant and benign hepatic, renal, and splenic nodules in dogs and cats based on perfusion patterns. The utility of contrast-enhanced ultrasonography in other applications is still under study. The aim of this study was to develop diagnostic criteria by contrast-enhanced ultrasonography in 8 client-owned adult dogs affected by urinary bladder transitional cell carcinoma with definitive diagnosis made by cytopathologic evaluation after suction biopsy. The contrast enhancement pattern and the quantification of blood flow parameters of this tumor were reported. RESULTS: Examinations with B-mode, Doppler ultrasonography and contrast-enhanced ultrasonography were performed in all not sedated dogs. Assessments of bladder masses and bladder wall infiltration were performed. Each dog received 2 bolus injections of sulfur hexafluoride during the contrast-enhanced ultrasonography. Quantitative analysis of the contrast-enhanced ultrasonography images were performed. For each dog, one region of interest was manually drawn around the entire tumor. Software analysis of contrast-enhanced time-intensity curves was used to identify peak enhancement, time to peak enhancement, regional blood volume, regional blood flow, and mean transit time. Contrast-enhanced ultrasonography showed an avid enhancement of the tumour tissue, with a heterogeneous or homogeneous pattern. The exam also showed the loss of planes between the lesion and the muscular layer. The presence of vascularized tissue through the bladder wall confirms the infiltrative feature of the tumour. Post-processing quantitative analysis showed a time-intensity curve with a rapid wash-in, a low level of signal intensity and a slow wash-out. CONCLUSIONS: Contrast-enhanced ultrasonography provided useful clinical information and defined a vascular enhancement patterns and calculated parameters associated with TCC. It may be a useful, noninvasive and reproducible tool for detecting these tumors in dogs.

Pilot Study on QTc Interval in Dogs Treated with Domperidone.

Domperidone is used as an immunomodulatory drug for Leishmania infantum infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported in humans. This pilot study evaluated the corrected QT (QTc) interval in dogs treated with domperidone for preventive or therapeutic management of leishmaniosis. The electrocardiogram and blood concentration of creatinine, urea nitrogen, sodium, potassium, and chloride were evaluated seven days before the start and on the last day of therapy in 17 dogs receiving domperidone for four weeks. In two dogs, the QTc interval was measured before and 2 h, 3 h, and 12 h after administration of the drug on the first day of treatment. After treatment, QTc measures and chloride concentrations increased significantly, although the QTc value slightly exceeded the upper reference limit only in one dog, and chloride concentrations were always normal. Creatinine concentrations significantly decreased after therapy. In the two dogs monitored at different times on the first day of treatment, QTc values were always normal. Domperidone caused a slight prolongation of QTc interval, and further studies should be made for a risk assessment in dogs with cardiac diseases, electrolytic imbalance, and in those receiving drugs increasing QT interval or competing with domperidone metabolism.

Assessment of testicular stiffness in fertile dogs with shear wave elastography techniques: a pilot study.

Ultrasound of the testes is important in the evaluation of breeding dogs, and recently advanced techniques such as Shear Wave Elastography (SWE) have been developed. This study focused on evaluation of normal testicular stiffness in healthy and fertile male dogs, employing both qualitative (2D-SWE) and quantitative (pSWE, 2D-SWE) techniques. Nineteen dogs of various medium-large breeds aged 3.39 ± 2.15 years, and with a history of successful reproduction were included after clinical, B-mode and Doppler ultrasound of testes and prostate, and semen macro and microscopic evaluations. pSWE involved square regions of interest (ROIs) placed at six different points in the testicular parenchyma, while 2D-SWE depicted stiffness with a color scale ranging from blue (soft) to red (stiff), allowing a subsequent quantification of stiffness by the application of 4 round ROIs. The results showed a mean Shear Wave Speed (SWS) of 2.15 ± 0.39 m/s using pSWE, with lower values above the mediastinum compared to below, and in the center of the testis compared to the cranial and caudal poles. 2D-SWE demonstrated a uniform blue pattern in the parenchyma, and a mean SWS of 1.65 ± 0.15 m/s. No significant differences were found between left and right testes, above and below the mediastinum, or among breeds. No correlations were observed between mean SWS and body condition score, age, testicular and prostatic volume. Weight was positively correlated with mean SWS only by 2D-SWE. By performing semen analysis and enrolling only healthy and fertile adult dogs, we ensured both structural and functional integrity of the testes. This pilot study represents a valuable baseline data for testicular stiffness by both pSWE and 2D-SWE with a Mindray US machine in medium-large sized healthy and fertile dogs, pointing out the potential role of SWE in the non-invasive fertility assessment and management of breeding dogs.

Prevalence and Features of Incidental Findings in Veterinary Computed Tomography: A Single-Center Six-Years' Experience.

Computed tomography (CT) is an advanced imaging technique that may lead to detect "incidentalomas", unexpected asymptomatic lesions found during unrelated examinations. Their clinical meaning and management are not clear for veterinarians, who risk unnecessary investigations that harm the patients. This study is a retrospective analysis that aims to investigate incidentalomas in CT exams and to describe their prevalence, location, types and follow-up, their correlations and associations with the species, breed, sex, and age of patients examined and with the kind and number of sites scanned. The reports of 561 CT scans performed in 512 dogs and 49 cats in a veterinary facility over six years were reviewed and compared to the clinical records of the patients. Eighty incidentalomas were found in 57 dogs and four cats. A significant positive correlation was found in dogs between age and the prevalence of incidentalomas. In dogs, the prevalence of incidentalomas was significantly higher in Boxers and in neck, thoracic, and abdominal scans. Spinal incidentalomas were the most common typologies in dogs. This study can represent a tool that allows clinicians to acquire greater awareness about incidentalomas and to carry out the evidence-based clinical management of them.

Contrast-Enhanced Ultrasonography (CEUS) in Imaging of the Reproductive System in Dogs: A Literature Review.

The use of contrast-enhanced ultrasound (CEUS) has been widely reported for reproductive imaging in humans and animals. This review aims to analyze the utility of CEUS in characterizing canine reproductive physiology and pathologies. In September 2022, a search for articles about CEUS in canine testicles, prostate, uterus, placenta, and mammary glands was conducted on PubMed and Scopus from 1990 to 2022, showing 36 total results. CEUS differentiated testicular abnormalities and neoplastic lesions, but it could not characterize tumors. In prostatic diseases, CEUS in dogs was widely studied in animal models for prostatic cancer treatment. In veterinary medicine, this diagnostic tool could distinguish prostatic adenocarcinomas. In ovaries, CEUS differentiated the follicular phases. In CEH-pyometra syndrome, it showed a different enhancement between endometrium and cysts, and highlighted angiogenesis. CEUS was shown to be safe in pregnant dogs and was able to assess normal and abnormal fetal-maternal blood flow and placental dysfunction. In normal mammary glands, CEUS showed vascularization only in diestrus, with differences between mammary glands. CEUS was not specific for neoplastic versus non-neoplastic masses and for benign tumors, except for complex carcinomas and neoplastic vascularization. Works on CEUS showed its usefulness in a wide spectrum of pathologies of this non-invasive, reliable diagnostic procedure.

Nontraumatic Paraureteral Urinoma in a Cat with Urolithiasis.

Urinoma is an encapsulated collection of urine due to a disruption in the collection system of the urinary tract. This condition is rarely reported in veterinary medicine. The aim of this study is to describe the clinical and diagnostic findings of a well-encapsulated paraureteral urinoma associated with urinary tract stones in a critical feline patient. The ultrasound examination of the abdomen revealed a well-defined collection of anechoic fluid containing the left kidney in the retroperitoneal space, while the radiographic examination revealed a loss of soft tissue contrast in the lumbar region. Both techniques confirmed the presence of stones in the bladder. Following the ultrasound-guided drainage of the lesion, the nature of the fluid was also confirmed to be urine. Due to the worsening of the cat's health, to better define the extent and genesis of the lesion, a positive contrast radiographic study was performed by means of an ultrasound-guided percutaneous injection of a contrast medium into the lesion, which highlighted a wide and homogeneous radiopaque area in the left retroperitoneal space. These findings were confirmed with a postmortem examination, corroborating the diagnostic suspicion of urinoma. The percutaneous contrast inoculation performed in this critically ill patient plays a role in the diagnostic process to reach a final diagnosis in cases in which the patient's clinical condition does not allow for performing an excretory positive contrast study.

How Owners of Epileptic Dogs Living in Italy Evaluate Their Quality of Life and That of Their Pet: A Survey Study.

Epilepsy is the most common chronic neurological disorder of dogs and requires a substantial commitment by the pet owner. The aim of this study was to evaluate how Italian owners of epileptic dogs receiving long-term treatment perceived their own quality of life (QoL) and that of their pet, using a list of key questions. A questionnaire was sent to owners of dogs affected by recurrent seizures and treated with antiepileptic drugs for at least three months. The questions included signalment, medical history and physical, social and psychological aspects associated with managing an epileptic dog. Eighty complete questionnaires were obtained. Most owners surveyed had a positive opinion on their dog's QoL and they did not believe that commitment to managing their animals was a limitation of QoL. Dog QoL, seizure, frequency and severity were considered the most important factors in evaluating the efficacy of the antiepileptic treatment. The evaluation of the different aspects of QoL can help veterinary professionals understand the need for correct and exhaustive information provided to owners and the development of therapeutic plans and follow up, corresponding to the needs of dogs and owners.

Bidimensional and Contrast-Enhanced Ultrasonography of the Spleen in Dogs Affected by Leishmaniosis.

Canine leishmaniosis (CanL) is responsible for splenic pathological changes. The main features detectable from ultrasound examination are splenomegaly and diffuse alterations of the echostructure. The study aimed to highlight whether these ultrasound changes are related to the severity of the disease or to a modification of splenic microvascularization that can be detected in vivo through contrast-enhanced ultrasonography (CEUS). Twenty-five adult dogs tested for CanL were enrolled in this prospective, controlled study and staged according to LeishVet guidelines. Bidimensional ultrasonography revealed that splenomegaly was seen in 50% of the affected dogs, and diffuse parenchymal changes were seen in more than 60% of dogs with splenomegaly, showing a positive correlation with severity of the disease; therefore, splenomegaly could be of prognostic significance. CEUS showed that a persistent heterogeneous distribution pattern appeared only in spleens with diffuse echostructure alterations. The evaluation of quantitative CEUS parameters regarding the volume and velocity of flow in three regions of interest did not show differences between affected and control dogs. Diffuse spleen microvascular modifications evidenced by CEUS were reported for the first time in dogs with CanL. In endemic areas, CanL could be included in the differential diagnoses list when detecting splenic alterations in dogs.

Feline Morbillivirus in Southern Italy: Epidemiology, Clinico-Pathological Features and Phylogenetic Analysis in Cats.

Feline morbillivirus (FeMV) was isolated for the first time in 2012 with an association with chronic kidney disease (CKD) suggested. This study aimed at investigating in cats from southern Italy FeMV prevalence and risk factors for exposure to FeMV, including the relationship with CKD; sequencing amplicons and analyzing phylogeny of PCR positive samples. Blood serum, K3EDTA blood and urine samples from 223 cats were investigated. Ten carcasses were also evaluated. FeMV RNA was detected in 2.4% (5/211) blood and 16.1% (36/223) urine samples. One carcass tested positive by qPCRFeMV from kidney, urinary bladder, and submandibular lymph nodes. Antibodies against FeMV were detected in 14.5% (28/193) cats. We followed up 27 cats (13 FeMV positive cats) and documented in some cases urine shedding after up to 360 days. Older and foundling cats and cats living in rescue catteries, were more frequently infected with FeMV. A significant correlation between FeMV and higher serum creatinine values or low urine specific gravity was found. FeMV positivity was significantly associated with retroviral infection, and the presence of some clinical signs apart from CKD clinicopathological markers. Our study highlights the possibility of a link between FeMV exposure and CKD and a general impairment of feline health.

Effects of topical 0.5% levobunolol alone or in association with 2% dorzolamide compared with a fixed combination of 0.5% timolol and 2% dorzolamide on intraocular pressure and heart rate in dogs without glaucoma.

The goal of glaucoma management is to reduce intraocular pressure (IOP) and maintain it at a level compatible with the health of the optic nerve. New therapies are constantly being sought. Topical instillation of levobunolol 0.5%, alone or with dorzolamide 2%, has a hypotensive effect on the IOP in healthy dogs, and levobunolol combined with dorzolamide produces a stronger hypotensive effect than the combination of timolol and dorzolamide. All animals tolerate these topical medications well with no signs of discomfort, and no ocular side effects have been observed. Levobunolol, alone or in combination with dorzolamide, induces bradycardia, as does timolol with dorzolamide.

Contrast-Enhanced Ultrasound in Cystic Endometrial Hyperplasia-Pyometra Complex in the Bitch: A Preliminary Study.

In cystic endometrial hyperplasia (CEH)-pyometra syndrome, toxic factors and endometrial remodeling culminate in changes characterized by exudative and degenerative inflammatory reaction. Recent studies on hemodynamic found an increased blood flow and lower vascular resistance in uterine arteries, suggesting color Doppler ultrasound as an adjunctive tool for quantitative assessment of endometrial vascularization during pyometra. The aim of this study was to assess, through contrast-enhanced ultrasound (CEUS) exam, the vascularization in endometrial microvessels in CEH-pyometra in order to evaluate the possibility of application in this syndrome. In twelve female dogs with clinical symptoms related to pyometra, B-mode, color Doppler and CEUS exams were performed. In CEH-pyometra uteri, histopathological examination revealed severe CEH and pyometra, immunohistochemical stain with CD 34 confirmed the presence of angiogenesis. CEUS exams revealed a widespread, intense and rapidly developing homogeneous enhancement of the hyperplastic endometrium, with absence of signal only in cystic areas. All parameters of the quantitative analysis were not significantly influenced by region of interest dimension and position. CEUS has the potential to improve clinical not invasive evaluations in the CEH-pyometra syndrome and virtually in CEH-mucometra.

Electrocardiographic Findings in Bitches Affected by Closed Cervix Pyometra.

Pyometra is considered the most common disease in intact bitches, being associated with potentially life-threatening disorders. Myocardial damage is a potentially life-threatening consequence of pyometra. The aim of this study was to describe the electrocardiographic patterns in bitches affected by closed cervix pyometra, to assess the clinical relevance of electrocardiographic changes with the occurrence of pyometra, and to relate their severity with laboratory and clinical findings. A total of 39 bitches with closed cervix pyometra and 10 healthy female dogs were included in this study. During the hospitalization, bitches underwent a complete physical examination. An electrocardiographic examination before the ovariohysterectomy was performed. Blood samples for biochemical and hematological analysis were also evaluated. Bitches suffering pyometra at least one arrhythmia 31/39 (79.4%), sinus tachycardia (22/39, 56.4%), ventricular premature complexes (9/39, 23%), increased amplitude of T wave (7/39, 17.9%), ST depression (4/39, 10.2%), second-degree atrioventricular block (2/39, 5.1%), increase of QT interval (2/39, 5.1%), sinus bradycardia (2/39, 5.1%), and first-degree atrioventricular block (1/39, 2.5%). Some bitches were also detected with low wave amplitude (17/39, 43.5%). Cardiac arrhythmias associated with canine pyometra are frequent events. These data suggest that arrhythmias may be the consequence of one or more factors that can occur during pyometra, such as myocardial damage, electrolyte/metabolic disorders, and/or sepsis.

An Unusual Case of Testicular Disorder in Sex Development of Arabian Mare (64,XX SRY-Negative).

A 3-year-old Arabian mare underwent medical examinations due to the presence of abnormalities of the reproductive apparatus and stallion behavior (nervous temperament, aggressiveness, masculine attitude). During the clinical visit, an anovulvar distance shorter than normal was observed; moreover, vulvar lips were dorsally fused except for the lower neckline, showing a blind ending from which a penis-like structure protruded. The ultrasound examination revealed the presence of a cervix and corpus of a uterus, hypoplastic uterine horns, and small gonads with an echogenicity similar to a testis. Blood testosterone levels ranged from 0.4 to 0.6 ng/mL. Cytogenetic analysis showed a normal female karyotype (2n = 64,XX), while PCR amplification of SRY and ZFY genes revealed the absence of a Y chromosome. At necroscopic examination, internal genitalia arising from the genital ridge in the form of masculine type structures were found, while those deriving from the Mullerian ducts were of feminine type. In addition, an infundibular portion of the salpinx at the cranial pole of the gonads was found. This is the first case in equine species of DSD 2n = 64,XX SRY-negative, with the simultaneous presence of male (hypoplastic testicles, epididymal portions, and a penis-like structure) and female (cervix, horn and body of a hypoplastic uterus) genital structures.

Two cases of feline ectromelia: autopodium ectromelia associated with humero-ulnar synostosis and zeugopodium ectromelia.

Congenital limb deformities are rarely reported in cats. This paper describes the radiographic findings of congenital forelimb malformations in two cats. The radiographic changes were suggestive of an autopodium ectromelia associated with humero-ulnar synostosis in one case and zeugopodium ectromelia in the other case. Congenital feline limb deformities are poorly documented and, to the authors' knowledge, this is the first time that humero-ulnar synostosis has been reported in cats.

Effects of size and location of regions of interest examined by use of contrast-enhanced ultrasonography on renal perfusion variables of dogs.

OBJECTIVE To determine effects of the size and location of regions of interest (ROIs) in the renal cortex of unsedated dogs on renal perfusion variables determined by use of contrast-enhanced ultrasonography (CEUS). ANIMALS 12 client-owned adult (1.5 to 2 years old) Labrador Retrievers (8 males and 4 females; mean ± SD body weight, 27 ± 1.6 kg). PROCEDURES Each dog received 2 bolus injections of sulfur hexafluoride during CEUS. Three small oval ROIs (area of each ROI, 0.11 cm(2)) located in a row with a distance of 1 mm between adjacent ROIs and 1 large oval ROI (area, 1 cm(2)) that encompassed the 3 smaller ROIs were manually drawn in the renal cortex. The ROIs were located at a depth of 1.5 to 2.0 cm in the near field of the renal cortex. Software analysis of time-intensity curves within each ROI was used to identify peak enhancement, time to peak enhancement, regional blood flow, and mean transit time. RESULTS The location and size of the ROIs of unsedated dogs did not cause significant differences in the mean values of the renal perfusion variables. CONCLUSIONS AND CLINICAL RELEVANCE The development of CEUS has provided a unique means for visually examining and quantifying tissue perfusion. Results of this study indicated that it was possible to use small or large ROIs during renal CEUS to evaluate renal perfusion in dogs.

Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic.

M40403, [manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26 pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]], is a low-molecular-weight, synthetic, manganese-containing superoxide dismutase mimetic that removes superoxide anions without interfering with other reactive species known to be involved in inflammatory responses (e.g., nitric oxide, NO and peroxynitrite, ONOO-). As such, M40403 represents an important pharmacological tool to dissect the roles of superoxide anion in acute and chronic inflammation. For this purpose, the pharmacological profile of M40403 was evaluated in a rat model of periodontitis. Periodontitis was induced in rats by placing a 2/0 braided silk around the lower left first molar. On day 8 the gingivomucosal tissue encircling the first molar was removed for biochemical and histological analysis. Ligation significantly increased inducible nitric oxide synthase activity and expression, and gingival tissue revealed increased neutrophil infiltration, lipid peroxidation and positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of M40403 (10 mg/kg daily for 8 days) significantly decreased all of the above-described markers of inflammation. This suggests compounds that inhibit the generation of superoxide anion, such as M40403 may be potentially useful for the treatment of periodontitis.

Carcinoma of the submandibular salivary glands with multiple metastases in a cat.

A 9-year-old neutered male domestic shorthair cat was presented because of coughing, dysphagia, and prostration. Examination revealed firm bilateral anterocervical swellings extensively adhered to the surrounding tissues. Anisocoria with left-side miosis was also evident. X-ray and ultrasound examinations along with a fine-needle aspiration biopsy were performed. Slides were stained with May-Grünwald Giemsa, and a diagnosis of salivary gland carcinoma was made. At surgery, the tumor was found to involve both submandibular salivary glands as well as adjacent lymph nodes and surrounding tissues. The cat was euthanized and necropsy was performed. The majority of tissues and organs examined histologically, including mandibular and retropharyngeal lymph nodes, soft palate, laryngopharynx and lungs, contained neoplastic cells whose appearance was consistent with adenocarcinoma. Bilateral salivary adenocarcinoma has not previously been reported in cats, and extensive metastases are rare.

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse.

OBJECTIVE: Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. The aim of this study was to investigate the effect of EPO on collagen-induced arthritis (CIA) in the mouse. METHODS: CIA was induced by intradermal injection of bovine type II collagen (CII) and Freund's complete adjuvant. Starting on day 25, some of the mice with CIA received daily subcutaneous injections of EPO (1,000 units/kg). Two other groups of mice received sham treatment alone or sham treatment followed by EPO treatment, respectively. Arthritis was assessed clinically, radiologically, and histologically. Cytokine and chemokine levels were measured, and neutrophil infiltration into inflamed joints was quantitated. Immunohistochemistry studies were performed to measure protein nitrosylation. Chondrocyte apoptosis was assessed by TUNEL assay. RESULTS: Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. Histopathologic features of CIA included erosion of the cartilage at the joint margins. Treatment with EPO starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26-35 and improved histologic status in the joints and paws. The degree of oxidative and nitrosative damage was significantly reduced in EPO-treated mice as indicated by decreased nitrotyrosine formation and poly(ADP-ribose) polymerase activation. Plasma levels of the proinflammatory cytokine tumor necrosis factor alpha were also significantly reduced by EPO treatment. In addition, EPO reduced the levels of apoptosis in chondrocytes in articular cartilage, as indicated by decreased TUNEL staining. CONCLUSION: These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.