Sex specific differences in hepatic and plasma lipid profiles in healthy cats pre and post spaying and neutering: relationship with feline hepatic lipidosis.

BACKGROUND: A link between lipid metabolism and disease has been recognized in cats. Since hepatic lipidosis is a frequent disorder in cats, the aim of the current study was to evaluate liver and plasma lipid dimorphism in healthy cats and the effects of gonadectomy on lipid profiling. From six female and six male cats plasma and liver lipid profiles before and after spaying/neutering were assessed and compared to five cats (three neutered male and two spayed female) diagnosed with hepatic lipidosis. RESULTS: Intact female cats had a significantly lower level of plasma triacylglycerides (TAG) and a higher liver level of the long chain polyunsaturated fatty acid arachidonic acid (AA) compared to their neutered state. Both male and female cats with lipidosis had a higher liver, but not plasma TAG level and an increased level of plasma and liver sphingomyelin compared to the healthy cats. CONCLUSION: Although lipid dimorphism in healthy cats resembles that of other species, intact female cats show differences in metabolic configuration that could predispose them to develop hepatic lipidosis. The increased sphingomyelin levels in cats with lipidosis could suggest a potential role in the pathogenesis of hepatic lipidosis in cats.

No up-regulation of the phosphatidylethanolamine N-methyltransferase pathway and choline production by sex hormones in cats.

BACKGROUND: Feline hepatic lipidosis (FHL) is a common cholestatic disease affecting cats of any breed, age and sex. Both choline deficiency and low hepatic phosphatidylethanolamine N-methyltransferase (PEMT) activity are associated with hepatic lipidosis (HL) in humans, mice and rats. The PEMT expression is known to be upregulated by oestrogens, protecting the females in these species from the development of HL when exposed to choline deficient diets. The aim of the present study was to evaluate the influence of sex hormones on choline synthesis via the PEMT pathway in healthy male and female cats before and after spaying/neutering, when fed a diet with recommended dietary choline content. RESULTS: From six female and six male cats PEMT activity was assayed directly in liver biopsies taken before and after spaying/neutering, and assessed indirectly by analyses of PEMT-specific hepatic phosphatidylcholine (PC) species and plasma choline levels. Hepatic PEMT activity did not differ between intact female and male cats and no changes upon spaying/neutering were observed. Likewise, no significant differences in liver PC content and PEMT-specific polyunsaturated PC species were found between the sexes and before or after spaying/neutering. CONCLUSION: These results suggest that choline synthesis in cats differs from what is observed in humans, mice and rats. The lack of evident influence of sex hormones on the PEMT pathway makes it unlikely that spaying/neutering predisposes cats for HL by causing PC deficiency as suggested in other species.

Assessment of misdiagnosis in small animal intensive care patients using the Modified Goldman criteria.

The postmortem examination can be used as a means of quality control for clinical diagnoses. A retrospective study on 300 dogs and cats that had been admitted to a small animal intensive care unit was performed comparing the clinical and postmortem findings, using the Modified Goldman criteria. All patient files were reevaluated for clinical diagnoses and all postmortem material was reevaluated for pathological diagnoses. After this, the Modified Goldman criteria were applied to score the discrepancies between them, and factors associated with the occurrence of an undiagnosed major unexpected finding were analyzed. The postmortem examination revealed additional findings in 65% of the cases. Major discrepancies, defined as those affecting treatment and possibly outcome of the patient, were present in 21.3% of the cases. The most frequently missed diagnoses detected at necropsy were pneumonia of various etiologies, meningitis/meningoencephalitis, myocarditis and generalized vasculitis. A shorter ICU stay was associated with increased odds of a major discrepancy. Conditions affecting the urinary or gastrointestinal system were negatively associated with major discrepancy.

Plasma sodium and potassium concentrations after hypophysectomy in dogs with corticotroph adenomas.

BACKGROUND: Electrolyte abnormalities, especially hypernatremia, are frequent complications after transsphenoidal hypophysectomy in dogs with pituitary-dependent hypercortisolism. OBJECTIVES: To describe electrolyte abnormalities after transsphenoidal hypophysectomy and to investigate possible associations between postoperative hypernatremia and clinical and surgical variables as well as with postoperative outcome. ANIMALS: One hundred and twenty-seven client-owned dogs. METHODS: Dogs with pituitary corticotroph adenomas that underwent transsphenoidal hypophysectomy were retrospectively included. Plasma sodium and potassium concentrations were measured -2, +2, +8, +24, and +48 hours from hypophysectomy. Clinical (breed, age, body weight, skull type, urinary cortisol/creatinine ratio, percentage of suppression to dexamethasone) and surgical variables (duration of anesthesia and surgery, pituitary dimensions) were compared to the development of hypernatremia. RESULTS: Postoperative hypernatremia developed in 46.5% (57/127) of dogs and hyponatremia in 6.3% (8/127). Plasma sodium concentration increased after surgery and peaked at 8 hours after surgery, normalizing after 24 to 48 hours. Plasma potassium concentration increased without exceeding the reference limit. No significant associations were found between clinical and surgical variables and hypernatremia, or between hypernatremia and postoperative death, long-term survival or recurrence. Surgery time was significantly longer in dogs that developed persistent diabetes insipidus (P = .02) and persistent diabetes insipidus occurred more frequently in dogs with enlarged pituitary glands (P = .01). CONCLUSION AND CLINICAL IMPORTANCE: Hypernatremia remains a frequent postoperative complication after transsphenoidal hypophysectomy but did not appear to have an impact on postoperative outcome. No predisposing factor to postoperative hypernatremia was identified. Variations in plasma potassium concentrations do not seem to influence postoperative outcome.

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats.

BACKGROUND: Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. OBJECTIVES: To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. ANIMALS: Twenty-five client-owned cats with spontaneous hypersomatotropism. METHODS: Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. RESULTS: Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis.

OBJECTIVES: The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). METHODS: Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), peroxisome proliferator-activated receptor-gamma (PPAR-γ), fatty acid synthase (FASN) and sterol regulatory element-binding factor (SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. RESULTS: In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different (P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group (P = 0.039). CONCLUSIONS AND RELEVANCE: The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs.

OBJECTIVE: To compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated. STUDY DESIGN: Prospective, randomised, blinded, positive-controlled parallel-group clinical study. ANIMALS: Forty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery. METHODS: After surgery, a loading dose of either DMED (25 microg m(-2)) or MOR (2500 microg m(-2)) followed by a 24-hour CRI of DMED (25 microg m(-2) hour(-1)) or MOR (2500 microg m(-2) hour(-1)) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan-Meier methodology. RESULTS: Forty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups. CONCLUSION / CLINICAL RELEVANCE: Dexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs.

Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

OBJECTIVES: The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). METHODS: Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. RESULTS: HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. CONCLUSIONS AND RELEVANCE: This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

Immunohistochemical evaluation of the activation of hepatic progenitor cells and their niche in feline lymphocytic cholangitis.

Objectives The aim of the study was to compare the hepatic progenitor cell niche in healthy feline livers and the liver tissue of cats with lymphocytic cholangitis. Methods Immunohistochemical stainings for vimentin, laminin, beta (ß)-catenin and Notch1 intracellular domain (NICD) were used on formalin-fixed liver biopsies from affected (n = 12) and unaffected cats (n = 2). Results All immunohistochemical markers used were expressed in more cells, or more intensely, in the liver tissue of cats with lymphocytic cholangitis than in the liver tissue of unaffected cats. Conclusions and relevance Enhanced expression of vimentin, laminin, cytoplasmic/nuclear ß-catenin and NICD in liver biopsies from cats with lymphocytic cholangitis indicates that the hepatic progenitor cell (HPC) niche is remodelled and activated. HPCs might provide insights into new regenerative treatment options for lymphocytic cholangitis in cats in the future.

Feline Hepatic Lipidosis.

Feline hepatic lipidosis (FHL) is a common and potentially fatal liver disorder. Although the pathophysiologic mechanisms of FHL remain elusive, there is an imbalance between the influx of fatty acids from peripheral fat stores into the liver, de novo liposynthesis, and the rate of hepatic oxidation and dispersal of hepatic TAG via excretion of very-low density lipoproteins. The diagnosis of FHL is based on anamnestic, clinical, and clinicopathologic findings, associated with diagnostic imaging of the liver, and cytology, or histological examination of liver biopsies. Fluid therapy, electrolyte correction and adequate early nutrition are essential components of the therapy for FHL.

Interstitial pneumonia and pulmonary hypertension associated with suspected ehrlichiosis in a dog.

BACKGROUND: In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process. PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology. CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs. Only one case of PH associated with CME has been reported worldwide. CASE PRESENTATION: A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea. The dog previously lived in the Cape Verdean islands. Physical examination showed signs of right-sided congestive heart failure and poor peripheral perfusion. Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing. Echocardiography showed severe pulmonary hypertension with an estimated pressure gradient of 136 mm Hg. On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia. A severe gamma hyperglobulinemia was also documented. Serology for Ehrlichia canis was highly positive. Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically. Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH. CONCLUSION: This report illustrates that CME might be associated with significant pulmonary disease and should be considered as a possible differential diagnosis in dogs presenting with dyspnea and secondary pulmonary hypertension, especially in dogs that have been in endemic areas. This is important because CME is a treatable disease and its secondary lung and cardiac manifestations may be completely reversible.

Prefabricated tracheal prosthesis with partial biodegradable materials: a surgical and tissue engineering evaluation in vivo.

Large and circumferential tracheal defects remain at this time an unsolved problem for reconstructive surgery. Many types of prosthetic and tissue grafts have been used but with limited comfortable results. Major complications are anastomotic dehiscence, graft ischemia and stenosis due to the poor vascularization of the prosthetic complex. We studied the in vivo behaviour of a prefabricated flap composed of a partially bioresorbable tracheal prosthesis and an arterio-venous vascular carrier. The prosthesis was made of a tubular skeleton of knitted Dacron (20 microm porosity) embedded within a bioresorbable poly-lactic-co-glycolic acid polymer (PLA(75)GA(25)) covering both sides. Fifteen New Zealand White rabbits were divided in three groups, depending on the time of examination (30, 90 and 180 days post-implantation). The prosthesis was implanted in the visceral space of the neck using the common carotid trunk and the internal jugular vein as vascular pedicle. The histological, immunohistochemical, and ESEM analyses of collected samples, showed a time-dependent process of tissue neoformation and neovascularization on the prosthetic material with a significant increase from 30 to 90 days post-implantation. In contrast, there was no statistically significant difference in the fibrovascular connective deposition from 90 to 180 days. This finding indicated the three months time as the best period for the tissue deposition and consequent hypothetical orthotopic transplantation of the prosthesis. Further in vivo studies are intended to confirm the results.