Neutrophil proteases are protective against SARS-CoV-2 by degrading the spike protein and dampening virus-mediated inflammation.

Studies on severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have highlighted the crucial role of host proteases for viral replication and the immune response. The serine proteases furin and TMPRSS2 and lysosomal cysteine proteases facilitate viral entry by limited proteolytic processing of the spike (S) protein. While neutrophils are recruited to the lungs during COVID-19 pneumonia, little is known about the role of the neutrophil serine proteases (NSPs) cathepsin G (CatG), elastase (NE), and proteinase 3 (PR3) on SARS-CoV-2 entry and replication. Furthermore, the current paradigm is that NSPs may contribute to the pathogenesis of severe COVID-19. Here, we show that these proteases cleaved the S protein at multiple sites and abrogated viral entry and replication in vitro. In mouse models, CatG significantly inhibited viral replication in the lung. Importantly, lung inflammation and pathology were increased in mice deficient in NE and/or CatG. These results reveal that NSPs contribute to innate defenses against SARS-CoV-2 infection via proteolytic inactivation of the S protein and that NE and CatG limit lung inflammation in vivo. We conclude that therapeutic interventions aiming to reduce the activity of NSPs may interfere with viral clearance and inflammation in COVID-19 patients.

Fatal gastritis and enterocolitis due to concurrent Helicobacter pylori and Campylobacter jejuni infection in a captive cheetah (Acinonyxjubatus).

A 3.5-year-old female cheetah (Acinonyx jubatus) died after a 10-day history of anorexia, regurgitation and diarrhoea despite symptomatic therapy. At gross post-mortem examination, the stomach was blood-filled with mucosal thickening and multifocal ulcerations. The intestinal mucosa was thickened and reddened, and the intestinal lumen was filled with dark red to black pasty content. Gastric histological lesions were compatible with gastritis due to Helicobacter infection, which was confirmed by polymerase chain reaction. Histology of the intestines revealed a severe necrotizing neutrophilic enterocolitis with abundant intralesional curved to spiral bacteria, corresponding to Campylobacter jejuni, which were subsequently isolated from both small and large intestinal contents. No other intestinal pathogens were detected despite thorough investigations. These findings suggest that C. jejuni may have played an aetiological role in the enterocolitis. Such an association has not been previously reported in non-domestic felids.

Relationships between soil and badger elemental concentrations across a heterogeneously contaminated landscape.

Understanding the links between environmental and wildlife elemental concentrations is key to help assess ecosystem functions and the potential effects of legacy pollutants. In this study, livers from 448 European badgers (Meles meles) collected across the English Midlands were used to investigate the relationship between elemental concentrations in topsoils and wildlife. Mean soil sample concentrations within 2 km of each badger, determined using data from the British Geological Survey's 'Geochemical Baseline Survey of the Environment', were compared to badger liver elemental concentrations, focusing primarily on Ag, As, Cd, Cr, Cu, K, Mn, Pb, Se, Zn. Generally, the badgers appeared to have elemental concentrations comparable with those published for other related animals, though Cu concentrations tended to be lower than expected. While there was no relationship between soil and badger liver concentrations for most biologically essential elements, biologically non-essential elements, specifically Pb, Cd, As, and Ag, were positively correlated between soil and badger livers. Lead and Cd, the elements with the strongest relationships between soils and badger livers, were primarily elevated in badgers collected in Derbyshire, a county with a millennia-long history of Pb mining and significant Pb and Cd soil pollution. Cadmium concentrations in badgers were also, on average, almost nine times higher than the local soil concentrations, likely due to Cd biomagnification in earthworms, a dietary staple of badgers. While badgers are good models for studying associations between soil and wildlife elemental concentrations, due to their diet, burrowing behaviours, and site fidelity, all flora and fauna local to human-modified environments could be exposed to and impacted by legacy pollutants.

Comparative pathogenesis of peste des petits ruminants virus strains of difference virulence.

Peste des petits ruminants (PPR) is an acute disease of small ruminants caused by a morbillivirus. Clinical observation of the disease in the field revealed that several species of small ruminants are affected to varying degrees. This difference in disease-related effects could depend either on the host or on the virulence of the virus strain. A previous study highlighted the difference in virulence between two strains of PPRV used to infect Saanen goats. For this breed, PPRV Morocco 2008 strain (MA08) was highly virulent while PPRV Côte d'Ivoire 1989 (IC89) strain induced mild disease. Experimental studies generally based on healthy and young animals do not permit exploration of the natural variability of the host susceptibility to PPRV. Therefore, building on the previous study on Saanen goats, the current study focussed on this breed of goat and used commercially available animals with an unknown history of infection with other pathogens. Results confirmed the previous disease pattern for PPRV IC89 and MA08 strains. Viral RNA detection, macroscopic and histological lesions were stronger for the highly virulent MA08 strain. We show here for the first time that viral RNA can be detected in the tissues of vaccinated animals. Viral RNA was also detected for the first time in serum samples, which is in agreement with the role of circulating immune cells in transporting the virus into host target organs. Thus, this study provides insight into the pathogenesis of strains of different virulence of PPRV and will help to better understand the onset of the disease.

Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component.

A limited number of species, including men and dogs, spontaneously develop prostate cancer (PC). The histological and molecular relevance of canine PC as a model for the disease in men remains controversial. To address this challenge, this study aimed to assess the histomorphology and expression of basal cell, urothelial and neuroendocrine markers [p63, high molecular weight cytokeratin (HMWCK), Uroplakin 3 (UPIII), neuron-specific enolase (NSE)] in canine PC (n = 41). Based on histomorphology, 10/41 (24%), 21/41 (51%) and 9/41 (22%) were classified as adenocarcinoma (AC), urothelial carcinoma (UC), and mixed carcinoma, respectively. Tumour inflammation was common, frequently severe [20/41 (49%)], and associated with neutering (p < .02) and urothelial differentiation (p < .02). Most (36/40, 90%) cancers contained only rare cells with basal cell marker expression or were negative. The expression of UPIII was absent or weak in the majority (33/38, 87%) of tumours, with moderate to strong staining in the remaining cases. NSE expression in PC was rare and limited to 2/14 (14%) cases. Tumour extension into benign ducts and glands was a common finding with presence in 17/39 (44%) of carcinomas with and without urothelial differentiation. In conclusion, we confirm that canine PC is characterized by absent or weak expression of basal cell and urothelial markers. Although rare, NSE expression, potentially indicating neuroendocrine differentiation, is reported for the first time in canine PCa. Intraductal carcinoma of the prostate with concurrent invasive PCa (IDCP-inv) is a frequent, not previously described, finding in dogs with PC.

Tuberculosis in badgers where the bovine tuberculosis epidemic is expanding in cattle in England.

Bovine tuberculosis (bTB) is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Wild badgers (Meles meles) play a role on its epidemiology in some areas of high prevalence in cattle, particularly in the UK and Republic of Ireland and increasingly in parts of mainland Europe. However, little is known about the involvement of badgers in areas on the spatial edge of the cattle epidemic, where increasing prevalence in cattle is seen. Here we report the findings of a study of found-dead (mainly road-killed) badgers in six counties on the edge of the English epidemic of bTB in cattle. The overall prevalence of Mycobacterium tuberculosis complex (MTC) infection detected in the study area was 51/610 (8.3%, 95% CI 6.4-11%) with the county-level prevalence ranging from 15 to 4-5%. The MTC spoligotypes of recovered from badgers and cattle varied: in the northern part of the study area spoligotype SB0129 predominated in both cattle and badgers, but elsewhere there was a much wider range of spoligotypes found in badgers than in cattle, in which infection was mostly with the regional cattle spoligotype. The low prevalence of MTC in badgers in much of the study area, and, relative to in cattle, the lower density of sampling, make firm conclusions difficult to draw. However, with the exception of Cheshire (north-west of the study area), little evidence was found to link the expansion of the bTB epidemic in cattle in England to widespread badger infection.

Phenotypic and Genomic Analysis of Cystic Hygroma in Pigs.

Cystic hygroma is a malformation of the lymphatic and vascular system and is recognized as a benign congenital tumor that affects humans and animals in the perinatal period. This congeni-tal disorder is rarely described in animals, and until today, cystic hygroma in pigs has not been described in the literature. In a purebred Piètrain litter with twelve live-born piglets, cystic hy-groma was noticed on the rump of two male pigs within the first week of life. In addition, a third case of a crossbred weaner (Large White × Landrace) was detected during a herd examina-tion. To rule out common differential diagnoses, e.g., abscess or hematoma, further clinical and pathological investigations were conducted. During clinical examination, a painless and soft mass, which was compressible, was detected on the rump of all affected animals. The ultra-sonographic examination revealed a fluid-filled and cavernous subcutaneous structure. In addi-tion, a puncture of the cyst was conducted, revealing a serosanguinous fluid with negative bacte-riological culture. In all cases, a necropsy was performed, showing that the animals had fluid-filled cysts lined by well-differentiated lymphatic endothelium. Based on the clinicopathological examination, cystic hygroma was diagnosed. Furthermore, SNP array genotyping and whole-genome sequencing was performed and provided no evidence for a chromosomal disorder. In the Piètrain family, several genome regions were homozygous in both affected piglets. None-theless, a dominant acting de novo germline variant could not be ruled out, and therefore differ-ent filtering strategies were used to find pathogenic variants. The herein presented lists of pri-vate variants after filtering against hundreds of control genomes provide no plausible candidate and no shared variants among the two sequenced cases. Therefore, further studies are needed to evaluate possible genetic etiology. In general, systematic surveillance is needed to identify ge-netic defects as early as possible and to avoid the occurrence of losses in the pig population.

Clostridium perfringens-Associated Necrotic Enteritis-Like Disease in Coconut Lorikeets (Trichoglossus haematodus).

Several outbreaks of necrotic enteritis-like disease in lorikeets, from which Clostridium perfringens was consistently isolated, are described. All lorikeets had acute, segmental, or multifocal fibrinonecrotizing inflammatory lesions in the small and/or the large intestine, with intralesional gram-positive rods. The gene encoding C. perfringens alpha toxin was detected by PCR (polymerase chain reaction) on formalin-fixed, paraffin-embedded (FFPE) tissues in 20 out of 24 affected lorikeets (83%), but it was not amplified from samples of any of 10 control lorikeets (P < .0001). The second most prevalent C. perfringens toxin gene detected was the beta toxin gene, which was found in FFPE from 7 out of 24 affected lorikeets (29%). The other toxin genes were detected inconsistently and in a relatively low number of samples. These cases seem to be associated with C. perfringens, although the specific type involved could not be determined.

Pathological findings in genital organs of bulls naturally infected with Besnoitia besnoiti.

Bulls chronically affected by bovine besnoitiosis can suffer from sterility. There is limited information about the distribution of Besnoitia cysts and their associated lesions within the male genital organs. This work describes the gross and histological abnormalities in the genital organs of 6 bulls chronically infected with Besnoitia besnoiti, including both clinically (n = 4) and subclinically (n = 2) affected cases. Parasitic cysts were observed in the genital organs of all the clinically affected bulls. The tissue cysts were most commonly found within the pampiniform plexus (4/4), where they were often seen within venous vascular walls and associated with vasculitis, followed by epididymis (3/4), tunica albuginea (2/4), and penis (1/4). In decreasing order of their frequency, observed abnormalities included seminiferous tubule degeneration, testicular fibrosis, testicular necrosis, lack of/or diminished numbers of spermatozoa, testicular atrophy, and Leydig cell hyperplasia. Only one of the subclinically infected bulls had few Besnoitia cysts within the pampinoform plexus, which was associated to small areas of necrosis and mineralization in the ipsilateral testicle. Results indicate that Besnoitia cysts and genital abnormalities are frequent in bulls chronically affected by bovine besnoitiosis, while they are mild and scarce in subclinically affected ones. Moreover, present data show that Besnotia-associated testicular lesions can occur without the presence of cysts within the testicular parenchyma. B. besnoiti cysts seem to have a tropism for the vascular structures of the spermatic chord, which may cause testicular abnormalities via vascular damage, reduced blood flow, and/or impaired thermoregulation and subsequently lead to the observed testicular lesions.

Retrospective study on transmissible viral proventriculitis and chicken proventricular necrosis virus (CPNV) in the UK.

Chicken proventricular necrosis virus (CPNV) is a recently described birnavirus, which has been proposed to be the cause of transmissible viral proventriculitis (TVP). The understanding of the epidemiology of both the virus and the disease is very limited. A retrospective investigation on TVP and CPNV in broiler chicken submissions from the UK from between 1994 and 2015 was performed with the aims of assessing the longitudinal temporal evolution of TVP and CPNV, and to review the histological proventricular lesions in the studied chickens. Ninety-nine of the 135 included submissions (73.3%) fulfilled the TVP-diagnostic criteria, while the remaining 36 submissions (26.7%) displayed only lymphocytic proventriculitis (LP). The first detection of CPNV by PCR dated from 2009. Results showed a rise in the number of both TVP and positive CPNV RT-PCR submissions from 2009 with a peak in 2013, suggesting that they may be an emerging or re-emerging disease and pathogen, respectively. Twenty-two out of the 99 submissions displaying TVP lesions (22%) and four out of the 36 (11%) submissions with LP gave positive CPNV RT-PCR results, further supporting the association between CPNV and TVP and confirming that CPNV is present in a low proportion of proventriculi that do not fulfil the TVP-diagnostic criteria. In addition, intranuclear inclusion bodies were observed in 22 of the submissions with TVP. The vast majority of these cases (21 of 22, 96%) gave negative CPNV RT-PCR results, raising the question of whether a virus other than CPNV is responsible for some of these TVP-affected cases.RESEARCH HIGHLIGHTSTVP and CPNV have been present in British broilers since at least 1994 and 2009, respectively.TVP and CPNV seem to be an emerging and re-emerging disease and pathogen, respectively.CPNV was detected in proventriculi with both TVP and LP-lesions.Viruses other than CPNV may be responsible for some TVP-affected cases.

Spongiform leucoencephalomyelopathy in border terriers: clinical, electrophysiological and imaging features.

A novel spongiform leucoencephalomyelopathy was reported in border terrier puppies in 2012 causing a shaking puppy phenotype, but no information regarding clinical progression, imaging or electrophysiological findings were available. The aim of the present study was to describe the clinical, electrophysiological and MRI features of this disease in seven dogs and compare them with human white matter disorders. All cases presented with cerebellar ataxia and severe generalised coarse body tremors, which started at three weeks of age. The three cases that were not euthanased showed slow but progressive improvement over several months. Brainstem auditory evoked response demonstrated a normal wave I, reduced amplitude of wave II and an absence of waves III-VII. MRI revealed bilateral and symmetrical T2-weighted hyperintensities affecting the brainstem and cerebellar white matter. Histological examination of the brain and spinal cord showed spongiform change affecting the white matter of the cerebellum, brainstem and spinal cord with decreased myelin content. In summary, this leucoencephalomyelopathy has a pathognomonic clinical presentation with defining MRI and electrophysiological characteristics, and it is the first report to describe a long-term improvement of this condition.

Mucosal injury following short-term tracheal intubation: A novel animal model and composite tracheal injury score.

OBJECTIVES: Postintubation laryngotracheal injury is common. Assessment of histopathological changes currently requires animal models. We set about developing a viable, resource effective animal model to study these effects and to develop a detailed tissue injury score. METHODS: Six pigs were anesthetized using a standard regimen. We intubated the tracheas using a standard endotracheal tube modified to include optical sensors. Animals were anesthetized for a duration of two to four hours, and their lungs were ventilated using a normoxic gas mixture. Following euthanasia, the tracheas were removed and underwent histological assessment by two independent veterinary pathologists. The histological lesions, including controls, were described and quantified, and two pathologists classified tissues according to a novel injury score. RESULTS: Mean duration of tracheal intubation was 191 minutes (SD ± 41.6). In all except one animal, cuff pressures were maintained in the range of 25-45 cmH20. Histopathological findings in all study animals showed more extensive changes than previously described with short-term intubation. Changes were seen in all mucosal layers consistent with acute, suppurative, and ulcerative tracheitis. The range of scores of the developed composite scoring system among the animals was wider than in earlier descriptions. There was a high percentage of agreement between both pathologists. CONCLUSIONS: We have described a novel tracheal injury score to assess pathological changes following short term intubation in a viable animal model. The scoring system distinguished between the test animals as well as controls and may be appropriate for continuing study of intubation injury. LEVEL OF EVIDENCE: 3.

The dog as an animal model for bladder and urethral urothelial carcinoma: Comparative epidemiology and histology.

Despite the recent approval of several novel agents for patients with metastatic urothelial carcinoma (UC), survival in this setting remains poor. As such, continued investigation into novel therapeutic options remains warranted. Pre-clinical development of novel treatments requires an animal model that accurately simulates the disease in humans. The aim of the present study was to evaluate the dog as an animal model for human UC. A total of 260 cases of spontaneous, untreated canine primary urethral and urinary bladder UC, were epidemiologically and histologically assessed and classified based on the current 2016 World Health Organization (WHO) tumor classification system. Canine data was compared with human data available from scientific literature. The mean age of dogs diagnosed with UC was 10.22 years (range, 4-15 years), which is equivalent to 60-70 human years. The results revealed a high association between UC diagnosis with the female sex [odds ratio (OR) 3.51; 95% confidence interval (CI) 2.57-4.79; P<0.001], surgical neutering (OR 4.57; 95% CI 1.87-11.12; P<0.001) and breed (OR 15.11 for Scottish terriers; 95% CI 8.99-25.41; P<0.001). Based on the 2016 WHO tumor (T), node and metastasis staging system, the primary tumors were characterized as T1 (38%), T2a (28%), T2b (13%) and T3 (22%). Non-papillary, flat subgross tumor growth was strongly associated with muscle invasion (OR 31.00; P<0.001). Irrespective of subgross growth pattern, all assessable tumors were invading beyond the basement membrane compatible with infiltrating UC. Conventional, not further classifiable infiltrating UC was the most common type of tumor (90%), followed by UC with divergent, squamous and/or glandular differentiation (6%). Seven out of the 260 (2.8%) cases were classified as non-urothelial based on their histological morphology. These cases included 5 (2%) squamous cell carcinomas, 1 (0.4%) adenocarcinoma and 1 (0.4%) neuroendocrine tumor. The 2 most striking common features of canine and human UC included high sex predilection and histological tumor appearance. The results support the suitability of the dog as an animal model for UC and confirm that dogs also spontaneously develop rare UC subtypes and bladder tumors, including plasmacytoid UC and neuroendocrine tumor, which are herein described for the first time in a non-experimental animal species.

Meningeal carcinomatosis and spinal cord infiltration caused by a locally invasive pulmonary adenocarcinoma in a cat.

CASE SUMMARY: A 12-year-old domestic shorthair cat was presented with acute non-painful hindlimb proprioceptive ataxia localising to T3-L3 spinal cord segments. MRI revealed paravertebral muscular hyperintensity on T2-weighted images at the level of T7-T8 vertebrae. The cat improved on conservative management but deteriorated 3 months later. Repeated MRI showed meningeal enhancement at the same level and hyperintensity of the paravertebral musculature extending to the right thoracic wall and pleural space on short tau inversion recovery images. Thoracic CT showed mineralised lesions of the right lung, restricted pleural effusion and expansile bone lesions affecting multiple ribs. The cat had been treated for pyothorax 5 years earlier but manifested no current respiratory signs. Cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis but no neoplastic cells. Biopsy of the affected muscles and cytology of the lung and pleural lesions suggested a malignant epithelial cell tumour. Post-mortem examination confirmed a pulmonary adenocarcinoma locally infiltrating the thoracic wall, T7-T8 vertebrae and the spinal cord white matter. Meningeal carcinomatosis was detected with neoplastic cells invading the ventral median fissure of the spinal cord. No metastases were observed in other organs, indicating that neoplastic cells reached the spinal cord by direct extension. RELEVANCE AND NOVEL INFORMATION: Spinal meningeal carcinomatosis has not been reported in dogs or cats with extraneural tumours but is a well-recognised condition in humans. A metastatic cause of meningeal enhancement should be considered in patients with neurological signs of unknown origin. Imaging findings and CSF results can be non-specific.

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics.

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.

Detection of transmissible viral proventriculitis and chicken proventricular necrosis virus in the UK.

Increasing evidence suggests that a new birnavirus, named chicken proventricular necrosis virus (CPNV), is the aetiological agent of transmissible viral proventriculitis (TVP). The present work aimed to explore the possible presence of both TVP and CPNV in the UK. Forty-four chickens showing TVP-compatible gross lesions were classified into three groups based on the histological lesions: (i) TVP-affected chickens: lymphocytic infiltration and glandular necrosis (n = 15); (ii) lymphocytic proventriculitis (LP)-affected chickens: lymphocytic infiltration without necrosis (n = 18); and (iii) without proventriculitis (WP): no lymphocytic infiltration or necrosis (n = 11). Nine proventriculi (seven out of 15 corresponding to TVP, and two out of 11 corresponding to LP) were positive for CPNV by reverse transcriptase polymerase chain reaction (RT-PCR). These results support the previously suggested idea of CPNV as causative agent of TVP. Moreover, these data show that CPNV can also be detected in a number of cases with LP, which do not fulfil the histological TVP criteria. Phylogenetic analysis of partial sequences of gene VP1 showed that British CPNV sequences were closer to other European CPNV sequences and might constitute a different lineage from the American CPNV. TVP cases with negative CPNV PCR results may be due to chronic stages of the disease or to the reduced PCR sensitivity on formalin-fixed paraffin-embedded tissues. However, involvement of other agents in some of the cases cannot totally be ruled out. As far as the authors are aware, this is the first peer-reviewed report of TVP as well as of CPNV in the UK, and the first exploratory CPNV phylogenetic study.

Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.

Remote effects of acute kidney injury in a porcine model.

Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.