Utfodring av hundar med akut gastroenterit på svenska djursjukhus och kliniker

Gastroenterit är en magtarminflammation som till viss del behandlas med hjälp av foder. Studier har visat att fodret spelar stor roll i behandlingen vilket gör att ett foder av bra kvalitet och sammansättning är betydelsefullt. Vilka egenskaper ett foder bör ha och hur utfodring bäst ska göras är vik-tigt för djursjukskötare och annan kliniskt verksam personal att känna till för att möjliggöra bästa återhämtning och tillfrisknande hos hunden. Syftet med detta arbete är att undersöka vilket eller vilka foder som an-vänds på svenska djursjukhus och kliniker samt vilka egenskaper ett foder bör ha vid behandling av gastroenterit hos hund. Undersökningen gjordes dels genom en enkätstudie och dels genom en kompletterande litteratur-studie. Enkäten skickades ut till 37 stycken svenska djursjukhus och kliniker med stationärvårdsavdelning och totalt kunde 29 enkätsvar användas för analys. De två mest frekvent använda fodren är Royal Canin Gastro Intestinal och Hill’s i/d. Smakligheten framgår av enkäten vara den främsta anledningen till att ett foder väljs, men även bra erfarenhet av fodrets effekt är en viktig faktor. Royal Canin Gastro Intestinal och Hill’s i/d har en liknande samman-sättning, men innehållet skiljer sig åt gällande ingredienser och mängden av vissa näringsämnen. Royal Canin Gastro Intestinal uppges av enkäten vara smakligare än Hill’s i/d vilket kan bero på ett högre protein- och fettinnehåll, medan Hill’s i/d i större utsträckning väljs utifrån bra erfarenheter av fodrets effekt. Huruvida hundar med gastroenterit ska svältas till en början eller inte är omdiskuterat, men detta börjar frångås då minskad tillgång på näringsäm-nen i tarmen är negativt för tarmslemhinnan och påverkar hundens ho-meostas. Den viktigaste egenskapen hos ett foder utformat för hundar med gastroenterit är hög smältbarhet, detta för att kompensera tarmarnas nedsatta förmåga att utföra digestion och absorption av näringsämnen. Smältbarheten är därför också den främsta egenskapen ingredienser väljs utifrån där animaliska proteinkällor och vitt ris är exempel på lämpliga komponen-ter. Även ett lågt till måttligt fettinnehåll är att föredra samt tillsats av fibrer med måttlig fermenterbarhet då fibrer har en viktig del i att behandla och förhindra diarré vilket är ett vanligt problem vid gastroenterit.Gastroenteritis is an inflammation in the gastrointestinal tract which is treat-ed in part using the diet. Studies have shown that the diet is an important part in the treatment, therefore it is important to choose a diet with suitable composition and nutritional properties. To enable the best possible recovery for the dog, the properties of the diet and how to best feed the dog is vital knowledge for veterinary nurses and all staff working clinically. The aim of this study is to review which diet is most commonly used at Swedish animal hospitals and clinics and what characteristics a diet for treatment of gastroenteritis in dogs should have. This was done through both a survey and a supplementary literature study. The survey was sent to 37 Swedish animal hospitals and clinics, with a care unit, out of which 29 survey responses were used for the analysis. The two most frequently used diets are Royal Canin Gastro Intestinal and Hill’s i/d. The palatability is shown to be the main reason for choosing a diet, however good experiences of the diets impact were also of importance. Royal Canin Gastro Intestinal and Hill’s i/d have a similar composition, but content differs regarding ingredients and levels of some nutrients. Royal Canin Gastro Intestinal was reported to be more palatable than Hill’s i/d, which could be due to the higher content of protein and fat, whilst Hill’s i/d to greater extent was chosen because of good clinical experience. Whether food should be withheld from dogs with gastroenteritis in the early stages of disease is disputed, however the trend is to not withhold food since reduced access to nutrients in the intestine is negative for the intestinal mucosa and affects the dog’s homeostasis. The most important characteristic in a diet formulated for dogs with gastroenteritis is high digestibility, this to compensate reduced ability in the intestine to digest and absorb nutrients. The digestibility is also the main reason to choose ingredients where animal protein sources and white rice are examples of suitable components. Furthermore, a low to moderate content of fat is favorable as well as a supplement with fiber of moderate fermentability which is useful to treat and prevent the common problem of diarrhea when dealing with gastroenteritis

Attainment of Brown Adipocyte Features in White Adipocytes of Hormone-Sensitive Lipase Null Mice

BACKGROUND: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. CONCLUSIONS: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage

Aspects on Immune Complex Handling and Complement Deficiency in Relation to Pathogenic Mechanisms in Systemic Lupus Erythematosus

The autoimmune disease Systemic Lupus Erythematosus is associated with hereditary deficieny of early components from the classical pathway of complement activation, but not with deficiency of complement component C3 or of the alternative pathway components. The classical pathway is involved in elimination of pathological immune complexes from the circulation by transport via complement receptor type 1 (CR1). Here it is shown that immune complex adherence to CR1 is dependent on the presence of sufficient amounts of C3, suggesting that impaired immune complex elimination is not the major mechanism of SLE disease pathogenesis. In the absence of complement component C2, but with C1q and C4 present, the alternative pathway could be enhanced to activate C3 sufficiently for CR1 adherence. This mechanism was sensitive to the physiological concentration of alternative pathway component factor B. Selective C4A isotype deficiency was shown to be of minor importance in immune complex adherence to CR1 compared to activation of C3. Phosphorylation of C3 by a protein kinase released from activated platelets could be shown to have an effect on immune complex adherence to CR1, but it was not established whether the effect resulted from differences in C3 deposition or in immune complex solubilisation. The complement system is also involved in phagocytosis of apoptotic cells. It was shown here that SLE patient sera induced apoptosis in monocytes from healthy donors in vitro. Induction of apoptosis correlated with complement activation in the sera. Soluble HLA class I molecules (sHLA-I) are known to induce apoptosis in T-cells. Serum level of sHLA-I was elevated in SLE patient sera and correlated with complement activation, but no connection was found between sHLA-I level and induction of apoptosis in monocytes

Hormone-sensitive lipase is necessary for normal mobilization of lipids during sub-maximal exercise.

For the working muscle there are a number of fuels available for oxidative metabolism, including glycogen, glucose and non-esterified fatty acids. Non-esterified fatty acids originate from lipolysis in white adipose tissue, from hydrolysis of VLDL-triglycerides or from hydrolysis of intramyocellular triglyceride stores. A key enzyme in the mobilization of fatty acids from intracellular lipid stores is hormone-sensitive lipase (HSL). The aim of the present study was to investigate the metabolic response of HSL-null mice challenged with exercise or fasting and to examine if other lipases are able to fully compensate for the lack of HSL. The results showed that HSL-null mice have reduced capacity to perform aerobic exercise. The liver glycogen stores were more rapidly depleted in HSL-null mice during treadmill exercise and HSL-null mice had reduced plasma concentrations of both glycerol and non-esterified fatty acids after exercise and fasting, respectively. The data support the hypothesis that in the absence of HSL mice are not able to respond to an exercise challenge with increased mobilization of the lipid stores. Consequently, the impact of the lipid sparing effect on liver glycogen will be reduced in the HSL-null mice, resulting in faster depletion of this energy source, contributing to the decreased endurance during sub-maximal exercise. Key words: Treadmill exercise, lipid metabolism, glycogen, skeletal muscle, liver

Quarternary Structure and Enzymological Properties of the Different Hormone-Sensitive Lipase (HSL) Isoforms

Background: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of energy in the form of fatty acids from intracellular stores of neutral lipids. The enzyme has been shown to exist in different isoforms with different molecular masses (84 kDa, 89 kDa and 117 kDa) expressed in a tissue-dependent manner, where the predominant 84 kDa form in adipocytes is the most extensively studied. Methodology/Principal Findings: In this study we employed negative stain electron microscopy (EM) to analyze the quarternary structure of the different HSL isoforms. The results show that all three isoforms adopt a head-to-head homodimeric organization, where each monomer contains two structural domains. We also used enzymatic assays to show that despite the variation in the size of the N-terminal domain all three isoforms exhibit similar enzymological properties with regard to psychrotolerance and protein kinase A (PKA)-mediated phosphorylation and activation. Conclusions/Significance: We present the first data on the quaternary structure and domain organization of the three HSL isoforms. We conclude that despite large differences in the size of the N-terminal, non-catalytic domain all three HSL isoforms exhibit the same three-dimensional architecture. Furthermore, the three HSL isoforms are very similar with regar

Serum concentrations of C4 isotypes and factor B in type I C2 deficiency suggest haplotype-dependent quantitative expression of MHC class III complement genes

The complement protein C4 exists as two isotypes, C4A and C4B, encoded by genes in the major histocompatibility complex (MHC) class III region. The serum concentrations of C4A4 were lower than those of C4B2 in serum from 19 individuals homozygous for type I C2 deficiency (p < 0.0002). These individuals all had the S042 complotype and most of them were homozygous for the haplotype HLA-B18,S042,DR2. In 14 individuals heterozygous for the C2Q0 gene and with the C4A4, C4B2 phenotype and in 51 individuals with the C4A3, C4B1 phenotype, the isotype concentrations were equal. Factor B concentrations in the C2-deficient individuals were lower than those in individuals with the C4A3, C4B1 phenotype (p < 0.0001). The findings strongly suggest that the quantitative expression of C4 isotypes and factor B is MHC haplotype dependent. C4 null alleles cannot be accurately determined by measuring relative C4 isotype serum concentrations

Binding of immune complexes to erythrocyte CR1 (CD35): difference in requirement of classical pathway components and indication of alternative pathway-mediated binding in C2-deficiency

Deficiency of complement components within the classical pathway is associated with increased risk for immune complex disease. However, C2-deficient individuals often have a mild disease and about 50% are healthy. To study the importance of the different components for immune complex clearance, bovine serum albumin (BSA)/anti-BSA complexes were opsonized in human serum and the binding to erythrocyte complement receptor type 1 (CR1, CD35) was measured in vitro. In C2-depleted serum the complexes were opsonized and bound to CR1 but the reaction needed a longer opsonization time than in normal human serum (NHS). In contrast, serum reagent lacking C1q, C4 or C3 did not promote binding in this assay system. We also demonstrated that elevated levels of factor B could restore binding of complexes to erythrocytes in C2-depleted serum via alternative pathway activation. These results indicate that in spite of lack of a complete classical pathway, C2-deficient individuals could retain some immune complex opsonizing activity via the alternative pathway. This finding could contribute to the understanding of differences in association between complement deficiency and immune-complex disease

A human and animal model-based approach to investigating the anti-inflammatory profile and potential of the 5-HT_2B receptor antagonist AM1030

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic eczematous lesions that are commonly treated with topical corticosteroids and calcineurin inhibitors. Side-effects and safety concerns associated with these agents restrict their use, and new, safe treatment options are therefore needed. Recent reports suggest that serotonin, i.e. 5-hydroxytryptamine (5-HT) and the 5-HT(2) receptor family may contribute to inflammation and pruritus in the skin. The objective of this particular study was to investigate the 5HT(2B) receptor antagonist AM1030 with respect to its anti-inflammatory profile and potential. METHODS: AM1030 was tested in a set of distinct human and rodent in vitro and in vivo models, differing with respect to e.g. T cell involvement, triggering stimulus, main read-outs and route of drug administration. The in vitro systems used were staphylococcal enterotoxin A (SEA)-stimulated human peripheral blood mononuclear cells, lipopolysaccharide (LPS)-stimulated human primary monocytes, LPS-stimulated human THP-1 monocytes and LPS-stimulated mouse primary macrophages. The in vivo systems used were LPS- and SEA-induced cytokine production in the mouse, antigen-induced arthritis in the rat, glucose-6-phosphate isomerase-induced arthritis in the mouse and delayed-type hypersensitivity reaction in the mouse. In addition, different cell populations were analyzed with respect to their expression of the 5-HT(2B) receptor at the mRNA level. RESULTS: AM1030 significantly reduced both T cell-dependent and T cell-independent inflammatory responses, in vivo and in vitro. Due to the low or absent expression of the 5-HT(2B) receptor on T cell populations, the influence of AM1030 in T cell-dependent systems is suggested to be mediated via an indirect effect involving antigen-presenting cell types, such as monocytes and macrophages. CONCLUSION: Based on the wide range of model systems used in this study, differing e.g. with respect to species, T cell involvement, triggering stimuli, route of drug administration and read-outs, our results suggest a broad anti-inflammatory effect of AM1030 and identify the 5-HT(2B) receptor as a promising future target for anti-inflammatory intervention, e.g. in AD