Coagulopathy secondary to chronic hepatopathy in three lizards

Liver disease is prevalent in reptiles, but the understanding of the secondary consequences of liver disease in reptile patients is far from understood. This case series details three lizards that developed coagulopathy secondary to hepatopathies. Two green iguanas (Iguana iguana) both diagnosed with severe hepatic fibrosis experienced coagulopathies—one with fatal exsanguination from a broken toenail and the second case with acute pulmonary hemorrhage. A Mali uromastyx (Uromastyx maliensis) diagnosed with severe hepatic lipidosis experienced acute severe respiratory distress secondary to acute tracheal hemorrhage. The occurrence of pulmonary or tracheal hemorrhage in two patients appears notable, however, more cases are needed to determine significance. All three cases had hepatopathies diagnosed by computed tomography, prior to the coagulation related complications. Based upon the cases presented here, it is recommended that coagulopathic sequelae of liver disease be considered in lizards with hepatopathies.

Associations between ultrasound measurements and hematochemical parameters for the assessment of liver metabolic status in Holstein–Friesian cows

Metabolic disorders, including hepatic lipidosis and ketosis, severely affect animal health status and welfare with a large economic burden in dairy herds. The gold standard for diagnosing hepatic lipidosis is the liver biopsy, which is impractical and invasive for the screening at farm level. Ultrasound (US) imaging is a promising technique for identifying liver dysfunction, but standardized specifications in physiological conditions are needed. Herein, we described the features of four US measurements, namely the liver predicted triacylglycerol (pTAG) content, liver depth (LD), and portal vein area (PVA) and depth (PVD) and we investigated their associations with a set of hematochemical (HC) indicators in 342 clinically healthy Holstein Friesian dairy cows. Liver pTAG content was negatively associated with hematocrit and positively with globulin, whereas PVA was negatively associated with thiol group levels, and LD positively with ceruloplasmin. We found significant interactions between some HC parameters and parity: in particular, creatinine, thiol groups and globulin for PVA, and aspartate aminotransferase, paraoxonase and ceruloplasmin for PVD. This study offers new insights on variations in liver function occurring after calving and pave the way for the potential use of minimally invasive techniques for prompt detection of metabolic disorders in dairy herds.

Degradation of lipid droplets by chimeric autophagy-tethering compounds

Degrading pathogenic proteins by degrader technologies such as PROTACs (proteolysis-targeting chimeras) provides promising therapeutic strategies, but selective degradation of non-protein pathogenic biomolecules has been challenging. Here, we demonstrate a novel strategy to degrade non-protein biomolecules by autophagy-tethering compounds (ATTECs), using lipid droplets (LDs) as an exemplar target. LDs are ubiquitous cellular structures storing lipids and could be degraded by autophagy. We hypothesized that compounds interacting with both the LDs and the key autophagosome protein LC3 may enhance autophagic degradation of LDs. We designed and synthesized such compounds by connecting LC3-binding molecules to LD-binding probes via a linker. These compounds were capable of clearing LDs almost completely and rescued LD-related phenotypes in cells and in two independent mouse models with hepatic lipidosis. We further confirmed that the mechanism of action of these compounds was mediated through LC3 and autophagic degradation. Our proof-of-concept study demonstrates the capability of degrading LDs by ATTECs. Conceptually, this strategy could be applied to other protein and non-protein targets.

Progressive increases in creatine kinase activity in an anorexic cat with necrotising myopathy

Case summary A 5-year-old castrated male domestic shorthair cat with weight loss and reduced appetite was evaluated for increased and progressively rising creatine kinase (CK) activity. The cat had recently been diagnosed with hepatic lipidosis. Muscle biopsy and histopathology revealed mild myonecrosis and phagocytosis without obvious inflammatory cell infiltrates. Resolution of necrotising myopathy was observed after a short course of anti-inflammatory prednisolone and nutritional supplementation. Relevance and novel information This is the first report of a necrotising myopathy in a cat associated with progressively increasing CK activity and decreased appetite. Anorexia in cats has been associated with increased CK activity, but an underlying cause of this CK elevation has only been postulated. Here we document muscle necrosis and muscle stiffness in a cat with anorexia.

Intracellular Ca2+ signaling and ORAI calcium release-activated calcium modulator 1 (ORAI1) are associated with hepatic lipidosis in dairy cattle

Fatty liver is a common metabolic disorder afflicting dairy cows during the periparturient period and is closely associated with endoplasmic reticulum (ER) stress. The onset of ER stress in humans and mice alters hepatic lipid metabolism, but it is unknown if such event contributes to fatty liver in dairy cows soon after parturition. ORAI1 is a key component of the store-operated Ca2+ entry mechanism regulating cellular Ca2+ balance. The purpose of this study was to investigate the role of ORAI1 on hepatic lipidosis via ER stress in dairy cows. Liver tissue biopsies were collected from Holstein cows diagnosed as healthy (n=6) or with hepatic lipidosis (n=6). Protein and mRNA abundance of ER stress-related targets, lipogenic targets or the transcription regulator SREBP1 and ORAI1 were greater in cows with lipidosis. In vitro, hepatocytes were isolated from four healthy female calves and used for culture with a 1.2 mM mixture of fatty acids (oleic, linoleic, palmitic, stearic, and palmitoleic acid) for various times (0, 3, 6, 9 or 12 h). As incubation time progressed, increases in concentration of Ca2+ and abundance of protein kinase RNA-like ER kinase (PERK), inositol requiring protein-1α (IRE1α), and activating transcription factor-6 (ATF6) protein in response to exogenous fatty acids underscored a mechanistic link among Ca2+, fatty acids and ER stress. In a subsequent study, hepatocytes were transfected with small interfering RNA (siORAI1) or the ORAI1 inhibitor BTP2 for 48 h or 2 h followed by a challenge with the 1.2 mM mixture of fatty acids for 6 h. Compared with control group, silencing or inhibition of ORAI1 led to decreased abundance of fatty acid synthesis (FASN, SREBP1 and ACACA) and ER stress-related proteins in bovine hepatocytes. Overall, data suggested that NEFA through ORAI1 regulate intracellular Ca2+ signaling, induce ER stress, and lead to lipidosis in isolated hepatocytes.

Hepatic lipidosis in fattening turkeys: A review

The conditions on turkey fattening farms, including management, housing, and feeding, have been constantly improved recently in favour of animal health. Many studies deal scientifically with poultry health. However, specifically concerning liver health, there are still open questions regarding the influence of dietary factors on the metabolism and function of the liver. Consideration of the factors that could influence and alter liver metabolism is therefore of critical relevance. The liver, as a major metabolic organ, is the main site of fat synthesis in turkeys. Under certain conditions, fat can excessively accumulate in the liver and adversely affect the birds’ health. The so-called hepatic lipidosis (HL) in fattening turkeys has been known for years. This disease has unacceptable economic and animal welfare impacts, with high animal losses up to 15% within only a few days. To date, little is known about the causes and the metabolic changes in fattening turkeys leading to HL despite the increasing focus on health management and animal welfare. To understand what is different in turkeys compared to other species, it is necessary to discuss the metabolism of the liver in more detail, including HL-associated gross and microscopic lesions. In the current review, aspects of liver structure and lipid metabolism with special regard to lipogenesis are explained to discuss all dietary factors attributing to the development and prevention of HL. As part of the prevention of the HL, dietetics measures can be helpful in the future.

Hepatogenous Photosensitivity Outbreak after Coccidiosis in Grazing Holstein Steers

Clinical signs of photosensitivity in cattle can occur sporadically and unpredictably. It is believed that cases of photosensitivity may be underreported, causing inaccurate and inflated reports of mortality. Additionally, because secondary photosensitization in grazing cattle occurs with liver damage or dysfunction, photosensitivity can have many potential or associated causes. This case links a previous occurrence of coccidiosis to an outbreak of photosensitivity in grazing Holstein steers. Grazing management staff first observed clinical signs of photosensitivity 17 days after an outbreak of coccidiosis and subsequent turnout to spring pastures. Clinical signs were observed in 25% of the population. The severity of photosensitivity was variable and ranged from blistered skin on the muzzle to sloughing of unpigmented epidermis and thinly haired regions. Severely affected cattle were removed from pasture, housed under shade, monitored for infection, and recovered without treatment. Mild cases remained on pasture and recovered without treatment. Photosensitivity did not reoccur in the cattle that remained on pasture or in mildly affected cattle returned to pasture. Photosensitivity did not appear to be associated with pasture weeds, a specific forage species, or variable or extreme weather conditions that could have resulted in mycotoxin production. The occurrence appears to have been a result of a previous and concurrent coccidiosis outbreak that caused secondary photosensitization through hepatic lipidosis caused by anorexia and dehydration associated with the severe coccidiosis. Although clinical signs appeared suddenly, cattle recovered quickly and without treatment.

Studies on Biomarkers of Hepatic Lipidosis in Transition Cows with Special Reference to Liver Ultrasonograhy, Liver Specific Enzymes and Acute Phase Proteins

Background: Use of novel biomarkers is the need of hour for prediction and early diagnosis of bovine production diseases such as hepatic lipidosis (HL). Liver ultrasonography and estimation of liver specific enzymes activities have been successfully used for diagnosis of HL. However, use of inflammatory mediator like tumor necrosis factor-á (TNF–á) or acute phase proteins (APPs) like C reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hp) as biomarkers of HL has not been elucidated. The present study was therefore designed to evaluate liver ultrasonography and serum APPs concentrations as early predictive biomarkers of bovine HL. Methods: This study included one hundred one (101) multiparous crossbred cows in advanced pregnancy from dairy farm in Punjab, India. The cows were grouped according to their transition stage i.e., Far off dry (FOD), close up dry (CUD) and Fresh (F). Liver ultrasonography along with hemato-biochemical analysis and estimation of acute phase proteins was carried out during different stages of transition period. Result: This study included 101 cows, of which 71 (70.3%) had ultrasonographic features of normal liver and 30 (29.7%) had ultrasonographic features of HL (Grade I, 10 cows; Grade II, 12 cows; Grade III, 8 cows). Cows with HL had significantly lower levels of hemoglobin (Hb), packed cell volume (PCV), total erythrocyte count (TEC), total plasma protein (TPP), glucose, total calcium (Ca) and zinc (Zn) and significantly higher levels of plasma urea nitrogen (PUN), non-esterified fatty acid (NEFA), beta hydroxyl butyric acid (BHBA), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glutamate dehydrogenase (GDH), lactate dehydrogenase (LDH), TNF–á, CRP, SAA and Hp compared to the negative controls. The APPs, liver ultrasonography, liver enzymes along with NEFA and BHBA could be used as biomarkers for prediction and early diagnosis of HL in cows.