Fatty acid supplementation and skin disease

The importance of dietary fatty acids to the health of the skin was recognized more than 60 years ago. Fatty acids are important in providing membrane fluidity and maintaining the cutaneous water permeability barrier. Fatty acids function as precursors of eicosanoids. Eicosanoids, which include prostaglandins and leukotrienes, influence cellular interactions, cellular proliferation, and inflammation. Certain diseases, such as atopy and hypothyroidism, are characterized by abnormalities in fatty acid metabolism. Dietary manipulations may be useful in the treatment of diseases mediated by eicosanoids.     

Fatty acid composition of serum lipids in atopic and healthy dogs

Fatty acids are increasingly used in the treatment of canine atopic dermatitis and their beneficial effects are documented in several prospective, controlled studies. Results from recent studies have indicated that atopic dogs have disordered fat metabolism, due to decreased desaturase activity. To further clarify these possible abnormalities, we examined serum fatty acid patterns in dogs with atopic dermatitis and normal controls. Atopic dermatitis was diagnosed according to the diagnostic criteria proposed by Willemse, after elimination of other possible causes of pruritic dermatitis. Both the relative and the absolute amounts of fatty acids in sera were determined by gas chromatography. Differences in the serum fatty acid pattern indicating a reduction in desaturase activity were not detected in atopic dogs when compared with controls.     

Plasma and skin concentrations of polyunsaturated fatty acids before and after supplementation with n-3 fatty acids in dogs with atopic dermatitis

OBJECTIVE: To determine essential fatty acid concentrations in plasma and tissue before and after supplementation with n-3 fatty acids in dogs with atopic dermatitis. ANIMALS: 30 dogs with atopic dermatitis. PROCEDURE: Dogs received supplemental flaxseed oil (200 mg/kg/d), eicosapentaenoic acid (EPA; 50 mg/kg/d)-docosahexaenoic acid (DHA; 35 mg/kg/d), or mineral oil as a placebo in a double-blind, placebo-controlled, randomized trial. Clinical scores and plasma and cutaneous concentrations of linoleic acid, arachidonic acid, alpha-linolenic acid (alpha-LLA), EPA, DHA, prostaglandin E2, and leukotriene B4 were determined. RESULTS: Total plasma concentrations of alpha-LLA and EPA increased and those of arachidonic acid decreased significantly with administration of EPA-DHA, and concentrations of alpha-LLA increased with flaxseed oil supplementation; nevertheless, there was no significant change in the concentrations of these fatty acids or eicosanoids in the skin. There was no correlation between clinical scores and plasma or cutaneous concentrations for any of the measured fatty acids or eicosanoids. CONCLUSION AND CLINICAL RELEVANCE: Results indicated that at the dose used, neither the concentrations of fatty acids in skin or plasma nor a decrease in the production of inflammatory eicosanoids was a major factor involved in the mechanism of action in dogs with atopy that responded to fatty acid supplementation.     

Serum concentrations of immunoglobulins G, A, and M in dogs with neoplastic disease

The concentrations of the three major classes of immunoglobulins (Ig) were determined in canine serum by single radial immunodiffusion against calibrated standards. Serum samples were collected from 121 dogs categorized into 3 groups: normal dogs (n = 34), those with lymphosarcoma (n =41), and those with malignant, solid neoplasms other than lymphosarcoma (n = 46). The mean value for serum IgM concentration in the group of dogs with lymphosarcoma was significantly (P less than or equal to 0.02) higher than was the mean IgM concentration of the normal dogs. Dogs with neoplasms other than lymphosarcoma had significantly increased serum concentrations of IgG and IgM antibodies. There was no significant difference in serum IgA concentration among the three groups. A wide range of Ig concentrations was in the serum of clinically normal dogs, as well as in dogs with neoplastic diseases. Although individual dogs with neoplasms had low serum Ig concentrations, the 81 dogs with neoplastic disease were generally able to synthesize Ig.     

Effect of oral ursodeoxycholic acid on bile acids tolerance tests in healthy dogs

OBJECTIVE: To determine whether oral administration of ursodeoxycholic acid (UDCA) to healthy dogs alters the results of the bile acids tolerance test. METHODS: UDCA (15 mg/kg once daily) was administered to 16 healthy dogs for 7 days. Health of the dogs was assessed by clinical examination, haematology, serum biochemistry and a bile acids tolerance test. Normal liver structure was confirmed by histopathology at the end of the study. Bile acids tolerance tests were performed before and at the end of the treatment period, with each dog serving as its own control. For the posttreatment bile acids tolerance test, UDCA was administered at the time of feeding. RESULTS: Pretreatment, the fasted serum total bile acid concentrations ranged between 0 and 9 micromol/L. In the majority of dogs, the postprandial total bile acid concentration was greater than the preprandial value, with a range of 0 to 16 micromol/L. The fasted total bile acid concentration was 0 micromol/L in most dogs (93.75%) after treatment with UDCA. Postprandial serum bile acids also remained within the reference range for the majority of dogs (93.75%) after UDCA treatment. A single dog had a postprandial bile acid concentration above the reference range, but the concentration was within the reference range when the assay was repeated the following day without concurrent administration of UDCA. The pre- and postprandial total serum bile acid concentrations were not significantly affected by UDCA treatment. CONCLUSION: The administration of UDCA does not alter the bile acids tolerance test of normal healthy dogs.     

The utility of uric acid assay in dogs as an indicator of functional hepatic mass

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.     

Identification,occurrence and clinical findings of canine hemoplasmas in southern Brazil

Hemoplasmas are ubiquitous pleomorphic and epicellular bacteria detected in erythrocytes in several species. In Brazil, studies on hemoplasmas have not included information on occurrence, clinical signs, and risk factors in dogs. This paper investigates the occurrence of hemoplasmas in dogs, focusing on risk factors and clinical status. Conventional PCR for the four types of canine hemoplasmas was performed in 331 blood samples collected from dogs clinically treated at a teaching veterinary hospital. Of all samples, 17/331 (5.1%) were positive for Mycoplasma haemocanis and 6/331 (1.8%) were positive for a ‘Candidatus Mycoplasma haemominutum-like’ organism. Risk factors included the presence of vectors, old age, dog bite wounds, and neoplastic diseases. In the multivariate analysis, a 4.40 odds ratio in dogs with vector-borne diseases indicated risk for hemoplasmosis. There was correlation between hemoplasma infection and neoplastic disease, suggesting that neoplastic conditions are a risk factor for hemoplasma infection in dogs.     

A comparison of clinical,magnetic resonance imaging and pathological findings in dogs with gliomatosis cerebri,focusing on cases with minimal magnetic resonance imaging changes‡

The primary study objective was to determine whether clinical examination and magnetic resonance imaging (MRI) can underestimate canine gliomatosis cerebri (GC); we also investigated immunohistochemical features. Seven dogs with GC were studied; four recruited specifically because of minimal MRI changes. Neuroanatomic localization and the distribution of MRI, gross and sub‐gross lesions were compared with the actual histological distribution of neoplastic cells. In six cases, clinical examination predicted focal disease and MRI demonstrated a single lesion or appeared normal. Neoplastic cells infiltrated many regions deemed normal by clinical examination and MRI, and were Olig2‐positive and glial fibrillary acid protein‐negative. Four dogs had concurrent gliomas. GC is a differential diagnosis for dogs with focal neurological deficits and a normal MRI or a focal MRI lesion. Canine GC is probably mainly oligodendrocytic. Type II GC, a solid glioma accompanying diffuse central nervous system neoplastic infiltration, occurs in dogs as in people.     

Assessment of ultrasonography and computed tomography for the evaluation of unilateral orbital disease in dogs

OBJECTIVE: To describe clinical, ultrasonographic, and computed tomographic (CT) features of confirmed neoplastic and nonneoplastic disease in dogs with unilateral orbital diseases, determine criteria to differentiate between the 2 conditions, and assess the relative value of ultrasonography and CT for the differential diagnosis of these 2 conditions. DESIGN: Prospective study. ANIMALS: 29 dogs with unilateral neoplastic orbital disease and 16 dogs with unilateral nonneoplastic orbital disease. PROCEDURES: Clinical history and results of physical and ophthalmologic examinations were recorded. Ultrasonographic and CT images were evaluated, and discriminating factors were identified to differentiate neoplastic from nonneoplastic diseases. Diagnostic value of ultrasonography and CT was assessed. RESULTS: Dogs with neoplastic disease were significantly older; had clinical signs for a longer time before initial examination; had more progressive onset of clinical signs; and more frequently had protrusion of the nictitating membrane, fever, and anorexia. The most discriminating factor for both imaging modalities was delineation of the margins (odds ratio was 41.7 for ultrasonography and 45 for CT), with neoplastic lesions clearly delineated more often. Ultrasonographically, neoplastic lesions were more frequently hypoechoic and homogeneous, with indentation of the globe and bone involvement evident more frequently than for nonneoplastic lesions. Mineralization was detected only with neoplasia. Fluctuant fluid was seen more frequently in dogs with nonneoplastic disease. Computed tomography more frequently revealed extraorbital involvement. Diagnostic value was similar for both imaging modalities. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonography and CT are valuable imaging modalities to assist in differentiating neoplastic from nonneoplastic unilateral orbital disease in dogs.     

Serum total prostatic and non-prostatic acid phosphatase in healthy dogs and in dogs with prostatic diseases

Total acid phosphatase (TAP), prostatic acid phosphatase (PAP) and non-prostatic acid phosphatase (NPAP) serum concentrations were determined using a spectrophotometric technique in 52 healthy dogs, 15 male dogs suffering from non-prostatic diseases and in 19 dogs suffering from prostatic diseases (12 dogs with benign prostatic hypertrophy and seven dogs with prostatic adenocarcinoma). TAP, PAP and NPAP serum concentrations did not differ between normal male and normal female dogs. Dogs with prostatic adenocarcinoma had significantly higher TAP, PAP and NPAP serum concentrations than dogs with benign prostatic hypertrophy, normal dogs and dogs with non-prostatic disease. The authors conclude that low serum concentrations of TAP and PAP do not rule out prostatic adenocarcinoma in the dog, but elevated concentrations can be useful criteria for the diagnosis of canine prostatic cancer.     

Flow cytometric expression of common antigens CD18/CD45 in blood from dogs with lymphoid malignancies: a semi-quantitative study

Flow cytometry is useful to study lymphoid malignancies since it allows both immunophenotyping of neoplastic cells and quantification of antigen expression. CD18 and CD45 are commonly exposed membrane antigens with different levels of expression on blood leukocyte and neoplastic cells. The aim of this retrospective study was to semi-quantitatively evaluate the expression of CD18 and CD45 in dogs with different lymphoid malignancies with blood involvement and to compare results with those from healthy dogs and dogs with reactive diseases. Blood samples from 13 dogs with precursor lymphoid malignancies, 20 with mature neoplasms (either chronic lymphocytic leukaemia or lymphoma), of different immunophenotypes, were compared with 24 healthy dogs and 12 dogs with different reactive diseases. The median fluorescence intensity (MFI) for CD18 and CD45 was recorded on lymphoid and granulocytic populations using dual colour flow cytometry, and the ratio between MFI for lymphoid and granulocytic populations (L/N ratio) was calculated to compare the results obtained in different sessions using an internal control (granulocyte fluorescence intensity). Significant decreases in the L/N ratio were detected in neoplastic samples for both CD18 (either precursors or mature versus controls) and CD45 (either precursors or mature versus control), while using MFI only slight differences were detectable in CD45 between precursors and controls. Neoplastic cells often exhibited lower expression of the L/N ratio for CD18, and mainly for CD45, most likely due to a less mature pattern than normal cells and/or to an aberrant quantitative expression of surface antigen. Moreover, more than 50% of neoplastic lymphoid cells exhibited L/N ratios that were not within the values observed in controls for at least one antigen. Altered L/N ratios, in particular decreases of CD45, were mainly observed in precursor neoplasms and in T-cell neoplasms. Detection of altered expression of common antigens, and in particular a L/N ratio for CD45 lower than a value of 103% may be useful as a confirmation of pseudo-clonality thus helping in differentiating reactive and neoplastic lymphocyte expansions.     

Quantification of plasma DNA as a prognostic indicator in canine lymphoid neoplasia

Dogs have a similar incidence of spontaneous cancers as people, and a noninvasive test to monitor disease status in dogs would be of great value. Humans with cancer often have increased levels of cell‐free circulating DNA in their plasma, which has shown promise for diagnosis, prognosis and detection of residual disease. We hypothesized that dogs with cancer have increased circulating DNA compared with healthy dogs or dogs with non‐neoplastic diseases. Plasma DNA was measured in 40 healthy dogs, 20 dogs with non‐neoplastic diseases and 80 dogs with cancer. The reference interval for plasma DNA in healthy dogs was 1–15 ng mL^?1. Dogs with lymphoma and lymphoid leukaemia had significantly higher concentrations (range: 0–91 ng mL^?1, P < 0.0001). Antigen receptor rearrangement assays suggest that plasma DNA had the same clonality as the primary lymphoid tumours. Dogs with lymphoid neoplasia and plasma DNA >25 ng mL^?1 had shorter remission times than those with < 25 ng mL^?1 (P= 0.0116). In contrast to humans, where increased plasma DNA is seen in many diseases, dogs with nonlymphoid malignancies and non‐neoplastic diseases had plasma DNA concentrations similar to healthy dogs. This study shows that a portion of dogs with lymphoid neoplasia have increased tumour‐derived plasma DNA, which serves as a negative prognostic indicator.     

Thoracic and abdominal organ uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) with positron emission tomography in the normal dog.

Positron emission tomography (PET) has found widespread application for staging and monitoring neoplastic diseases in humans. PET is becoming more available in veterinary medicine, therefore biodistribution of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) in normal dogs is needed for lesion interpretation in disease states. A large field-of-view (FOV) PET scanner with a 70 cm bore diameter and a 53-cm FOV was used in this study to acquire dynamic 18FDG uptake data from parenchymal organs in seven normal dogs. A 2-h, dynamic list-mode acquisition was initiated simultaneously with intravenous 18FDG injection. Regions of interest (ROIs) were manually drawn over liver, spleen, left and right renal cortices, left ventricular free wall, and thymus. Standardized uptake values (SUVs) of these organs were calculated for 24 5-min frames over the 2-h acquisition. This SUV data from parenchymal organs of normal dogs compares favorably with those of normal humans and will be used in ongoing canine studies using PET to evaluate various diseases.     

Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis

Glucocorticoids (GCs) are a large group of drugs used to treat a range of inflammatory, autoimmune and neoplastic diseases in dogs. Glucocorticoids have been linked to disturbances in calcium metabolism and skeletal disorders in humans, yet their effects at therapeutically effective dosages in dogs with spontaneous diseases are poorly understood. Serum concentrations of calcium, phosphate, vitamin D metabolites and plasma concentrations of parathyroid hormone and ionised calcium together with urinary fractional excretion of calcium and phosphate, were measured in 16 dogs with atopic dermatitis before and 6weeks after standard dosage prednisolone treatment (0.93-1.06mg/kg) every other day after 7days of treatment with the same dosage once daily. The severity of their physical signs, as assessed by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS), decreased in all dogs following prednisolone treatment. There was no significant difference in any of the biochemical parameters measured following prednisolone treatment. This study indicates that prednisolone, used at a therapeutically effective dose, has minimal impact on calcium metabolism in dogs with atopic dermatitis.     

Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.     

Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis

Plasma amino acid concentrations were measured in 36 dogs diagnosed with superficial necrolytic dermatitis (SND) via skin biopsy. The median age of the dogs was 10 years, and 27 out of 36 (75%) were male. Twenty-two out of 36 (61%) of the dogs were accounted for by six breeds; West Highland white terriers (six), Shetland sheepdogs (five), cocker spaniels (four), Scottish terriers (three), Lhasa apsos (two) and Border collies (two). The mean concentration (+/- standard deviation) was calculated for each measured plasma amino acid and compared to previously documented concentrations of plasma amino acids measured in dogs with acute and chronic hepatitis. The ratio of branched chain amino acids to aromatic amino acids in the dogs with SND was 2.6, slightly lower than that in normal dogs. The mean plasma amino acid concentrations for dogs with SND were significantly lower than for dogs with acute and chronic hepatitis. A metabolic hepatopathy in which there is increased hepatic catabolism of amino acids is hypothesized to explain the hypoaminoacidaemia seen in SND.     

Liver disease in dogs with tracheal collapse

BACKGROUND: Hepatopathy in dogs with chronic respiratory diseases is poorly recognized. The aim of this study was to evaluate liver parameters alanine transferase, alkaline phosphatase, and glutamate dehydrogenase, as well as basal and stimulated bile acid concentration, in dogs with tracheal collapse. HYPOTHESIS: Dogs with tracheal collapse have hepatopathy. ANIMALS: 26 dogs with tracheal collapse. MATERIALS AND METHODS: Gall bladder contraction was stimulated by intramuscular injection of a synthetic cholecystokinin analogue (ceruletide). Twelve healthy Beagle dogs and 30 dogs of various breeds investigated previously without evidence of hepatic, gastrointestinal, or respiratory diseases served as control. Amelioration of liver variables was assessed after stent implantation. RESULTS: Twelve of 26 (46%) dogs had increased serum activity of 2 or more liver enzymes. Serum basal bile acid concentrations were high in 24 of 26 dogs. Twenty- and 40-minute stimulated bile acids were significantly higher in dogs with tracheal collapse (64.2 +130.0/-43.0 micromol/L and 82.6 +164.0/-57.1 micromol/L) compared to the control dogs (7.0 +/- 3.6 micromol/L and 6.4 +/- 3.5 micromol/L). All twelve dogs reevaluated after a median of 58 days (48-219 days) had a normal breathing pattern and significantly decreased 20 and 40 minutes stimulated bile acids (50.0 +92.7/-32.8 micromol/L, 52.8 +97.6/-34.3 micromol/L; P = .0043), whereas plasma liver enzyme activities were not significantly influenced. CONCLUSION AND CLINICAL IMPORTANCE: There was a significant hepatic dysfunction in the majority of dogs with a tracheal collapse. Liver function should be routinely assessed in dogs with severe respiratory disease.     

Vascular endothelial growth factor concentrations in body cavity effusions in dogs

Vascular endothelial growth factor (VEGF) has potent angiogenic, mitogenic, and vascular permeability enhancing properties specific for endothelial cells. VEGF is present in high concentrations in inflammatory and neoplastic body cavity effusions and has been implicated in the pathogenesis of neoplastic and inflammatory effusion formation. In this study, VEGF was quantitated by solid-phase enzyme-linked immunoadsorbent assay (ELISA) in samples of pericardial, pleural, and peritoneal effusions (N = 38) from dogs (N = 35) with neoplastic and non-neoplastic diseases. VEGF was detected in 37 of 38 effusions (median, 754; range, 18-3,669 pg/mL) and was present in much higher concentrations than in previously established normal concentrations for canine plasma (median, < 1 pg/mL; range, < 1-18 pg/mL) or in those previously noted in the plasma of dogs with hemangiosarcoma (HSA; median, 17 pg/mL; range, < 1-67 pg/mL). In 4 dogs with HSA, the concurrent plasma VEGF concentration was much lower than in the abdominal effusion (P = .029). No significant correlation was demonstrated between VEGF effusion concentration and effusion total protein content or nucleated cell count. Mean VEGF concentrations were significantly higher in pericardial (median, 3,533; range, 709-3,669 pg/mL) and pleural effusions (median, 3,144; range, 0-3,663 pg/mL) compared to peritoneal effusions (median, 288; range, 18-2,607 pg/mL; P < .05). There was no marked difference demonstrated between effusions associated with malignant and nonmalignant diseases. Further studies are necessary to elucidate the role of VEGF in body cavity effusion formation in dogs.     

Evaluation of serum L-phenylalanine concentration as indicator of liver disease in dogs: a pilot study

Because essential amino acids are metabolized in the liver, liver diseases may impair their catabolism. In this study, serum L-phenylalanine concentrations in 28 dogs with liver diseases were compared with those of 28 healthy dogs and 13 dogs with nonhepatic diseases. Dogs with liver diseases had significantly increased L-phenylalanine serum concentrations compared to healthy dogs (P<0.001) and to those with nonhepatic diseases (P<0.01). There were no significant differences among the L-phenylalanine serum concentrations of dogs with different degrees of liver diseases. The sensitivity and specificity of L-phenylalanine to fasting bile acids were comparable.     

THORACIC AND ABDOMINAL ORGAN UPTAKE OF 2-DEOXY-2-[18F]FLUORO-d-GLUCOSE (18FDG) WITH POSITRON EMISSION TOMOGRAPHY IN THE NORMAL DOG

Positron emission tomography (PET) has found widespread application for staging and monitoring neoplastic diseases in humans. PET is becoming more available in veterinary medicine, therefore biodistribution of 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) in normal dogs is needed for lesion interpretation in disease states. A large field-of-view (FOV) PET scanner with a 70 cm bore diameter and a 53-cm FOV was used in this study to acquire dynamic ¹⁸FDG uptake data from parenchymal organs in seven normal dogs. A 2-h, dynamic list-mode acquisition was initiated simultaneously with intravenous ¹⁸FDG injection. Regions of interest (ROIs) were manually drawn over liver, spleen, left and right renal cortices, left ventricular free wall, and thymus. Standardized uptake values (SUVs) of these organs were calculated for 24 5-min frames over the 2-h acquisition. This SUV data from parenchymal organs of normal dogs compares favorably with those of normal humans and will be used in ongoing canine studies using PET to evaluate various diseases.