Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.

Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments ("2 cycle treatment") lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. DATA AVAILABILITY: This study does not include data deposited in public repositories. Data are available on request to the corresponding authors.

Cross-Sectional Serosurvey of Companion Animals Housed with SARS-CoV-2-Infected Owners, Italy.

We conducted a serologic survey among dogs and cats in Italy to detect antibodies against severe acute respiratory syndrome virus 2 (SARS-CoV-2). We found that SARS-CoV-2 seroprevalence was higher among cats (16.2%) than dogs (2.3%). In addition, seroprevalence was higher among animals living in close contact with SARS-CoV-2-positive owners.

Repeated oral administration of low doses of silver in mice: tissue distribution and effects on central nervous system.

BACKGROUND: Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery. RESULTS: There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT. CONCLUSIONS: Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.

Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia.

BACKGROUND: Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 h after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS). RESULTS: Compared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 h post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day. CONCLUSIONS: The results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Haematological and biochemical reference intervals in healthy racing and retired Italian Greyhounds.

In view of the enormous variability of dog breeds, breed-specific reference intervals (RIs) are recommended for use in veterinary clinical decision-making. The aim of this study was to determine whether RIs of the general canine population may be applied to the Italian Greyhound (Piccoli Levrieri Italiani or PLI), and to generate breed-specific RIs, where appropriate. Sixty-three privately owned clinically healthy fasted dogs were examined. Routine haematology and biochemistry were performed on 58 enrolled patients using the ADVIA 120 haematology analyzer and the Cobas Mira system, respectively. Changes in haematological and biochemical parameters depending on sex, age and attitude (resting vs. running dogs) were investigated. The results of PLI were compared with the RIs of the general canine population. In those cases in which these RIs were not validated, new RIs were generated according to the guidelines of the American Society of Veterinary Clinical Pathology. Pre-existing RIs were considered valid based on the recommendations by the Clinical & Laboratory Standards Institute (CLSI). RIs were higher for mean corpuscular haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), cell haemoglobin concentration mean (CHCM) and lower for large unstained cells (LUC). A wider discrepancy between pre-existing and newly established RIs was found for some ADVIA parameters regarding red blood cell (RBC) or reticulocyte morphology. For total protein and cholesterol the new RIs were wider than the pre-existing ones, while albumin, calcium and iron were higher. This study suggests that most of the RIs published in veterinary textbooks cannot be validated for PLIs.

SYSTEMATIC EVALUATION OF 106 LABORATORY REFERENCE DATA ARTICLES FROM NONDOMESTIC SPECIES PUBLISHED FROM 2014 TO 2016: ASSESSING COMPLIANCE WITH REFERENCE INTERVAL GUIDELINES.

Population-based reference intervals (RIs) are vital tools used to characterize health and disease based on laboratory values. The science and statistical basis for RI generation have evolved over the past 50 yr. Current veterinary-specific guidelines by the American Society of Veterinary Clinical Pathology exist for establishing RIs from nondomestic and wild animals. A list of 35 items that should be included during generation and publication of reference data was distilled from the currently available RI guidelines. The archives of five peer-reviewed journals were searched and 106 articles presenting laboratory reference data from nondomestic or wildlife species were identified and each reviewed by two authors to determine compliance with the list of 35 items. A compliance score was calculated as the number of articles that fulfilled the item out of the number where it would have been appropriate to fulfill the item. Most articles reported the number of reference individuals (compliance score 0.98), their partitioning demographics (compliance score 0.95), and sample collection and handling practices (compliance scores 0.97 and 0.96, respectively). Common deficiencies included omitting discussion of the validation status of the analytical methods for the species being evaluated (compliance score 0.12), documentation of use of exclusion criteria (compliance score 0.51), outlier detection (compliance score 0.43), appropriate statistical methods for the reference population (compliance score 0.34), and calculation and presentation of confidence intervals around the reference limits (compliance score 0.35). Compliance scores were not statistically different when stratified on the number of individuals in the largest and smallest evaluated group or the format of the article (full vs short format). Articles that cited RI generation guidelines fulfilled more of the required steps and provided a more complete description of their data (compliance score 0.74) than those that did not cite guidelines (compliance score 0.58). Additional attention to the science of and recommendations for RI generation is recommended to strengthen the utility of published data.

Long-Term Study on the Effects of Housing C57BL/6NCrl Mice in Cages Equipped With Wireless Technology Generating Extremely Low-Intensity Electromagnetic Fields.

The recent development of mouse cages equipped with monitoring wireless technology raised questions on the potential effects on animals induced by electromagnetic fields (EMFs) generated by electronic boards positioned underneath the cages. The aims of this study were to characterize the EMF produced by digitally ventilated cages (DVC) and perform a clinicopathological study on mice maintained in DVC for up to 1 year. The EMFs were measured in empty individually ventilated cages (IVC) and DVC. Male (n = 160) and female (n = 160) C57BL/6NCrl mice were randomly housed in IVC and DVC in a single rack, 4 mice per cage. Body weight and food and water consumption were recorded at 14-day intervals. At sacrifice (days 60, 120, 180, and 365), body and testes weight was measured, and necropsy, hematology, bone marrow cytology, histology, and immunohistochemistry for cleaved-caspase 3 on the testes were performed. Digitally ventilated cages produced extremely low-intensity electric fields ranging from 5 Hz to 3 GHz. No exposure-related clinical signs and mortality occurred. Occasional statistical differences in body weight, food and water consumption, hematology, bone marrow, and histopathology were recorded, but considered without biological or clinical relevance. In conclusion, long-term maintenance in DVC had no definite effects on C57BL/6NCrl mice.

Detection of hereditary bisalbuminemia in bottlenose dolphins (Tursiops truncatus, Montagu 1821): comparison between capillary zone and agarose gel electrophoresis.

BACKGROUND: Hereditary bisalbuminemia is a relatively rare anomaly characterized by the occurrence of two albumin fractions on serum protein separation by electrophoresis. In human medicine, it is usually revealed by chance, is not been clearly associated with a specific disease and the causative genetic alteration is a point mutation of human serum albumin gene inherited in an autosomal codominant pattern. This type of alteration is well recognizable by capillary zone electrophoresis (CZE), whilst agarose gel electrophoresis (AGE) not always produces a clear separation of albumin fractions. The aims of this study is to report the presence of this abnormality in two separate groups of related bottlenose dolphins and to compare the results obtained with capillary zone and agarose gel electrophoresis. RESULTS: Serum samples from 40 bottlenose dolphins kept under human care were analyzed. In 9 samples a double albumin peak was evident in CZE electrophoresis while no double peak was noted in AGE profile. Since only an apparently wider albumin peaks were noted in some AGE electrophoretic profiles, the ratio between base and height (b/h) of the albumin peak was calculated and each point-value recorded in the whole set of data was used to calculate a receiver operating characteristic curve: when the b/h ratio of albumin peak was equal or higher than 0.25, the sensitivity and specificity of AGE to detect bisalbuminemic samples were 87 and 63 %, respectively. The bisalbuminemic dolphins belong to two distinct families: in the first family, all the siblings derived from the same normal sire were bisalbuminemic, whereas in the second family bisalbuminemia was present in a sire and in two out of three siblings. CONCLUSIONS: We report for the first time the presence of hereditary bisalbuminemia in two groups of related bottlenose dolphins identified by means of CZE and we confirm that AGE could fail in the identification of this alteration.

Clinicopathological and Molecular Analysis of Aqueous Humor for the Diagnosis of Feline Infectious Peritonitis.

BACKGROUND: This study was designed to assess the diagnostic utility for FIP of cytology, protein measurement and RT-PCR for feline coronaviruses (FCoV) on aqueous humor (AH), since little information is currently available. METHODS: AH samples (n = 85) were collected post-mortem from 13 cats with effusive FIP (E-FIP), 15 with non-effusive FIP (NE-FIP) and 16 without FIP, to perform cytology (n = 83) and RT-PCR (n = 66) and to calculate their sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR-). The protein concentration was measured on 80 fluids. RESULTS: The proportion of RT-PCR positive samples did not differ among groups, while positive cytology was more frequent in samples with FIP (p = 0.042) or positive RT-PCR (p = 0.007). Compared with other groups, the protein concentration was higher in samples with NE-FIP (p = 0.017), positive RT-PCR (p = 0.005) or positive cytology (p < 0.001). The specificity of cytology together with RT-PCR, cytology alone, RT-PCR alone and cytological proteinaceous background were 90.0%, 84.6%, 70.0%, 61.5%, and the LRs 3.48, 2.65, 1.83, 1.64, respectively. However, their sensitivities were low (34.8-63.0%) and their LR- high (0.60-0.72). CONCLUSIONS: Based on the LR+, cytology and/or RT-PCR may support the diagnosis when the pre-test probability of FIP is high. The concentration of intraocular protein is a promising marker, especially in NE-FIP.

Measurement of Feline Alpha-1 Acid Glycoprotein in Serum and Effusion Using an ELISA Method: Analytical Validation and Diagnostic Role for Feline Infectious Peritonitis.

BACKGROUND: Alpha-1 acid glycoprotein (AGP) may support a clinical diagnosis of feline infectious peritonitis (FIP). In this study, we assessed the analytical and diagnostic performances of a novel ELISA method to measure feline AGP. METHODS: AGP was measured in sera and effusions from cats with FIP (n = 20) or with other diseases (n = 15). Precision was calculated based on the coefficient of variation (CV) of repeated testing, and accuracy was calculated by linearity under dilution (LUD). RESULTS: The test is precise (intra-assay CVs: <6.0% in individual samples, <15.0% in pooled samples; inter-assay CVs <11.0% and <15.0%) and accurate (serum LUD r2: 0.995; effusion LUD r2: 0.950) in serum and in effusions. AGP is higher in cats with FIP than in other cats in both serum (median: 1968, I-III interquartile range: 1216-3371 µg/mL and 296, 246-1963 µg/mL; p = 0.009) and effusion (1717, 1011-2379 µg/mL and 233, 165-566 µg/mL; p < 0.001). AGP discriminates FIP from other diseases (area under the receiver operating characteristic curve: serum, 0.760; effusion, 0.877), and its likelihood ratio is high (serum: 8.50 if AGP > 1590 µg/mL; effusion: 3.75 if AGP > 3780 µg/mL). CONCLUSION: This ELISA method is precise and accurate. AGP in serum and in effusions is a useful diagnostic marker for FIP.

Increased Erythrocyte Sedimentation Rate in Dogs: Frequency in Routine Clinical Practice and Association with Hematological Changes.

(1) Background: the erythrocyte sedimentation rate (ESR) has been reported to increase in some infectious or inflammatory diseases in dogs, but no information on the frequency of increases in a routine clinical setting exists. The aim of this study was to assess the frequency of an increased ESR in dogs and to investigate its possible association with hematologic changes; (2) Methods: A total of 295 EDTA blood samples were randomly selected from the routine caseload of the Veterinary Teaching Hospital. Samples were grouped in controls and in pathologic groups based on the clinical presentation. A routine hemogram was performed, then the ESR was measured using the instrument MINI-PET; (3) Results: compared with controls, the ESR was significantly higher in all the pathologic groups, except for the hematological disorders group. The highest ESR was found in samples from dogs with chronic kidney disease or inflammation, followed by those from dogs with mild chronic disorders, severe/acute diseases, tumors and urinary disorders. The ESR negatively correlated with hematocrit and positively with neutrophil counts. (4) Conclusions: The ESR increases more frequently in dogs with clinically evident inflammation or CKD, but also in several other conditions, likely as a consequence of anemia and acute phase response.

Automated hematological cell count using sysmex XN-1000V in Testudo hermanni: Agreement with manual count.

Mediterranean area represents the main habitat of Testudo hermanni. Clinical signs of disease of these tortoises are non-specific, making the hematology results crucial in revealing underlying pathological conditions. However, accurate automated identification of blood cell populations is hampered by the presence of nucleated erythrocytes (NRBC) and thrombocytes (Thr), necessitating manual methods such as counting chambers. The aim of the study was to assess the performance of the novel automated hematology analyzer Sysmex XN-1000 V, which includes a a specific channel (WNR) for counting NRBC, in accurately identify and quantify the different blood cell populations of Testudo hermanni. Additionally, its agreement with manual counts was evaluated. Fifty heparinized blood samples were initially counted using the Neubauer improved chamber and then analysed twice with Sysmex XN-1000 V. Thirteen out of 50 samples were instrumentally counted again after 48 h to assess the inter-assay precision. All WNR scattergrams were re-analysed using an ad hoc gate panel to differentiate two populations: NRBCs (weak fluorescence signal) and WBC + Thr (high fluorescence signal). Sysmex XN-1000 V demonstrated optimal intra- and inter-assay precision for NRBCs (CV 0.98% ± 1.96; 1.31% ± 2.98) and moderate precision for WBC + Thr (CV 9.24% ± 16.61; 12.69% ± 10.35). No proportional nor constant errors were observed between the methods for both the populations. The instrumental NRBC counts were consistently slightly lower, while WBC + Thr counts were slightly higher compared to manual counts. These findings suggest that Sysmex XN-1000 V can be used for analyzing cell populations in heparinized blood of Testudo hermanni. However, specific instrumental reference intervals are suggested.

Blood gases, acid-base, and metabolic alterations in calves with bronchopneumonia diagnosed via clinical signs and thoracic ultrasonography: A cross-sectional study.

BACKGROUND: Bronchopneumonia (BP) in calves potentially causes systemic changes. OBJECTIVES: To describe metabolic, arterial blood gas, and acid-base disorders in calves with BP diagnosed by thoracic ultrasound (TUS), Wisconsin score (WISC), and combinations of WISC and TUS. ANIMALS: Two hundred thirty-one dairy preweaned dairy calves from 13 dairy farms. METHODS: Cross-sectional study. Each calf sequentially underwent arterial blood gas evaluation, WISC score, venous sampling, and TUS. Calves were grouped based on a single diagnostic method and combination of WISC and 2 TUS cutoffs (≥1 cm; ≥3 cm) as healthy, upper respiratory tract infection, subclinical BP, and clinical BP. RESULTS: Oxygenation and acid-base variables were unaffected. Glucose concentration in TUS-affected calves was significantly lower (P < .001) than in healthy calves (median ≥TUS1cm = 5.2 mmol/L 25%-75% interquartile range [IQR] 4.5-6.1,

Diagnosis of Septic Body Cavity Effusion in Dogs and Cats: Cytology vs. Bacterial Culture.

The elective test for the determination of the effusions etiopathogenesis is represented by physico-chemical analysis and cytology. Nevertheless, the bacterial culture and antibiotic sensitivity tests are crucial for setting therapy and for the outcome. This study compared cytology with microbiology in the etiologic diagnosis of exudative body cavity effusions in dogs and cats collected from October 2018 to October 2022. All samples underwent aerobic and anaerobic culture and cytology examination. Bacterial identifications were confirmed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, whereas cytological samples were blindly evaluated either in May Grunwald-Giemsa (MGG) or Gram-stained samples by two board-certified clinical pathologists. A moderate agreement (κ = 0.454) between cytology and bacterial culture was revealed. The sensitivity of the cytological evaluation in our study ranged from 38.5% to 67.9%, and the specificity ranged from 88.9% to 100%, depending on the type of the effusion, so cytology may not be representative of the etiopathogenesis, whereas bacterial culture can misidentify or fail to isolate the correct pathogen for difficult in vitro growing due to the presence of inhibitory substances or contamination. Cytology and bacterial culture results for exudative body cavity effusions in dogs and cats can be misleading if conducted separately, so these two tests should be performed together to increase diagnostic accuracy.

Lipoprotein profiles in Miniature Schnauzer dogs with idiopathic hypertriglyceridemia and hypercortisolism.

Miniature Schnauzer dogs (MSs) are predisposed to both idiopathic hypertriglyceridemia (iHTG) and hypercortisolism (HCort). To our knowledge, the lipoprotein profiles of MSs with iHTG have not been compared to those with HCort. We analyzed cholesterol and triglyceride concentrations and lipoprotein fractions in 4 groups of MSs: normotriglyceridemia (NTG) without concurrent disease (Healthy-NTG), HCort and NTG (HCort-NTG), HCort and HTG (HCort-HTG), and iHTG. Lipoprotein fractions were assessed by lipoprotein electrophoresis and compared between groups. Fifty-one plasma samples were analyzed. Twenty-five dogs had NTG (16 Healthy-NTG, 9 HCort-NTG) and 26 dogs had HTG (7 iHTG, 19 HCort-HTG). Dogs with iHTG or HCort-HTG had significantly higher cholesterol concentrations than Healthy-NTG dogs. Dogs with HCort-HTG had higher cholesterol than HCort-NTG dogs. There was a significantly higher low-density lipoprotein (LDL) percentage in iHTG and HCort-HTG dogs than HCort-NTG dogs. HCort-HTG dogs also had lower high-density lipoproteins (HDL) than HCort-NTG dogs. It was not possible to readily distinguish MSs with iHTG from MSs with HCort-HTG or Healthy-NTG using lipoprotein electrophoresis fractions. The diagnosis of iHTG remains a diagnosis by exclusion.

Clinical and Clinico-Pathological Observations of the Erythrocyte Sedimentation Rate in Dogs Affected by Leishmaniosis and Other Inflammatory Diseases.

The erythrocyte sedimentation rate (ESR) has been used in canine medicine in several disorders, above all, to evaluate levels of inflammation. This study evaluated the ESR in canine leishmaniosis (CanL) and other inflammatory conditions. Three groups of dogs were examined: CanL affected dogs without clinical signs (INFECTED group, #25) or with clinical signs (SICK group, #43) and dogs affected by acute or acute-on-chronic conditions (OTHER DISEASE group, #65). The ESR was compared with acute phase proteins or reactants either positive or negative (leukogram, fibrinogen, iron, unsaturated iron binding capacity, ferritin, haptoglobin, and albumin) and immunological markers (gamma-globulins, IgG, and IgM). The ESR was higher in the SICK group than in the INFECTED group (median 39 vs. 11 mm/h; p < 0.0001), as well as in the OTHER DISEASE than in the INFECTED groups (median 41 vs. 11 mm/h; p < 0.0001). The ESR appeared outside the reference range for all dogs in the SICK and OTHER DISEASE groups and almost with similar values (mm/h; median 39, 95% CI 31-51 vs. 41, 95% CI 12-87; p > 0.05). The extent of changes in ESR can help to establish the severity of CanL and other inflammatory disorders. As a point-of-care test, the ESR can be used to screen dogs for unhealthy conditions, and its values correlate with the severity of any disease, including CanL.

Prospective Application of the Erythrocyte Sedimentation Rate (ESR) as a Possible Inflammatory Marker in Feline Patients.

The application of the erythrocyte sedimentation rate (ESR) in feline medicine is currently unavailable, while in canine medicine it has been rediscovered due to the introduction of an automated ESR device. Our aims were to (1) define the reference interval (RI) of the ESR in healthy cats, (2) evaluate the ESR values between healthy and ill cats, (3) evaluate relationships between the ESR and some inflammatory markers, and (4) assess ESR changes in different durations of illness (acute, chronic, or acute-on-chronic). A prospective multicentric cohort study on 200 client-owned cats: 57 healthy cats and 143 ill cats for the other aims. Healthy cats were blood donors, or young cats underwent desexing procedures. Ill cats with full clinical medical records, hematobiochemical profiles, and diagnostic procedures to reach a final diagnosis were included. The ESR was performed with MINI-PET using the same K3-EDTA tubes used for CBC, with no additional sample required. The total leukocyte count (WBC), neutrophil-to-lymphocyte ratio (NLR), fibrinogen, serum amyloid A, and albumin/globulin ratio (A/G) were concurrently measured. Based on the clinical presentation and the final diagnosis, cats were classified as having the following: acute, chronic, and acute-on-chronic conditions. The RI of the ESR ranged between 1 and 23 mm/h. Ill cats showed a significantly higher ESR (median 29 mm/h; range 12-46 mm/h) than healthy cats (median 10 mm/h; range 1-12 mm/h; p < 0.0001). The ESR was positively correlated only with fibrinogen (p < 0.001; r = 0.43). Cats with acute-on-chronic diseases had the highest ESR (median 47 mm/h; range 35-56 mm/h) compared with acute (median 16 mm/h; range 14-42 mm/h; p=0.003) and chronic cats (median 14 mm/h; range 10-31 mm/h; p < 0.0001). Although further studies are needed, the ESR could be a useful ancillary inflammatory marker in cats, specifically in cats with acute diseases, with or without an underlying chronic condition.

The use of serum paraoxonase-1 to assess inflammation in horses with colitis serum paraoxonase-1 in horses with colitis.

BACKGROUND: Paraoxonase-1 (PON-1) has been suggested as a marker of inflammation and oxidative stress in horses and could potentially be used for prognostication in horses with colitis. OBJECTIVES: Assessment of PON-1 in horses with colitis and comparison of two methods. METHODS: Serum PON-1 was measured by two methods (paraoxon and p-nitrophenyl acetate) in 161 horses with colitis and 57 controls. Follow-up samples obtained during hospitalization were available from 106 horses with colitis. The two methods were compared. RESULTS: Serum PON-1 was significantly lower in horses with colitis than in healthy horses (P < .0001 for both methods) as well as in nonsurvivors compared with survivors (P = .0141 [paraoxon-based method] and P < .0001 [p-nitrophenyl acetate-based method]), but with marked overlap between groups. PON-1 activity did not change parallel to a change in inflammatory status in response to treatment when assessed at admission and in up to seven follow-up samples. Admission PON-1 activity could not reliably classify horses as survivors or nonsurvivors, with sensitivity and specificity ranging between 53.1% and 72.9%. Results from the two methods were comparable. CONCLUSIONS: Both methods reliably measured serum PON-1 activity. Significant differences in PON-1 activity were found between healthy horses and horses with colitis and between survivors and nonsurvivors. However, PON-1 activity varied considerably within groups. Both the proposed reference intervals as well as alternative cutoff values resulted in suboptimal diagnostic and prognostic performance, and the use of serum PON-1 in horses with colitis thus seems to add little to existing diagnostic and prognostic markers.

Clinicopathological findings in non-human primate recipients of porcine renal xenografts: quantitative and qualitative evaluation of proteinuria.

BACKGROUND: Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. The detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential graft rejection. In this study, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function was supported only by the transplanted organ. METHODS: Eight bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a single kidney from α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59, and α1,2-fucosyltransferase. In addition to hematological and biochemical analyses, quantitative and qualitative analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE), respectively. RESULTS: The main hematological and biochemical changes recorded after transplantation were a progressive anemia and a severe and progressive decrease in total proteins. In urine samples, the UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation, but bands consistent with mixed (i.e., tubular and glomerular) proteinuria were observed in all samples collected post-transplantation. CONCLUSIONS: The study of clinicopathological changes in cynomolgus monkey renal xenograft recipients provides a valid help in monitoring the health conditions in the post-transplant period. Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey renal xenograft recipients may be considered a valid, inexpensive, and less time-consuming method than more sophisticated techniques in monitoring proteinuria. Proteinuria and presence of low molecular weight (LMW) proteins were consistently found in urine after transplantation, independent of fluctuations in renal function.

Variation of proteinuria in dogs with leishmaniasis treated with meglumine antimoniate and allopurinol: a retrospective study.

A retrospective study was performed using 53 client owned dogs with leishmaniasis to determine whether the degree of proteinuria, evaluated by the urine protein/creatinine ratio (UP/C), changes following treatment with meglumine antimoniate and allopurinol. Medical records of dogs with leishmaniasis in clinical stage C (according to the Canine Leishmaniasis Working Group staging system) and either proteinuric or borderline proteinuric (according to the International Renal Interest Society [IRIS] staging system) were reviewed. All dogs were treated with meglumine antimoniate and allopurinol for 4-8 wk. After treatment, UP/C, total protein, and total globulin significantly decreased and albumin and the albumin/globulin ratio (A/G) increased. After treatment, 7 of the 53 dogs (13.4%) became nonproteinuric following either a proteinuric or borderline proteinuric stage. Moreover, 12 of the 53 proteinuric dogs (22.6%) changed their stage to borderline proteinuric. The antileishmaniasis treatment with meglumine antimoniate in combination with allopurinol in dogs significantly reduced the degree of proteinuria in a short period of time. The results of the current study may be useful to the veterinary practitioner in the clinical management of canine leishmaniasis (CanL) in dogs with proteinuric chronic kidney disease.