Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours

The pharmacokinetic profile, tolerability and efficacy of benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride (BP‐C1) were studied in dogs with mammary cancer. A three‐level response surface pathway designed trial was performed on seven dogs. At each level BP‐C1 was administered subcutaneously daily for 7 days followed by a 7‐day rest period in a dose escalating manner. Adverse events according to VCOG‐CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two‐compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half‐life was 125 h. The maximum tolerated dose of BP‐C1 was estimated to be above 0.46 mg kg−1. A significant reduction in VCOG‐CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumourspublishedVersio

Renal histomorphology in dogs with pyometra and control dogs, and long term clinical outcome with respect to signs of kidney disease

<p>Abstract</p> <p>Background</p> <p>Age-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature.</p> <p>Methods</p> <p>Dogs with pyometra were examined retrospectively for evidence of secondary renal damage and persisting renal disease through two retrospective studies. In Study 1, light microscopic lesions of renal tissue were graded and compared in nineteen dogs with pyometra and thirteen age-matched control bitches. In Study 2, forty-one owners of dogs with pyometra were interviewed approximately 8 years after surgery for evidence ofclinical signs of renal failure in order to document causes of death/euthanasia.</p> <p>Results</p> <p>Interstitial inflammation and tubular atrophy were more pronounced in dogs with pyometra than in the control animals. Glomerular lesions classified as glomerular sclerosis were present in both groups. No unequivocal light microscopic features of glomerulonephritis were observed in bitches in any of the groups.</p> <p>Two bitches severely proteinuric at the time of surgery had developed end stage renal disease within 3 years. In five of the bitches polyuria persisted after surgery. Most bitches did not show signs of kidney disease at the time of death/euthanasia.</p> <p>Conclusion</p> <p>Tubulointerstitial inflammation was observed, but glomerular damage beyond age-related changes could not be demonstrated by light microscopy in the dogs with pyometra. However, severe proteinuria after surgery may predispose to development of renal failure.</p

Identitet i skrift - en komparativ karakteranalyse av Ask og Karl Ove i henholdsvis Sangen om den røde rubin og Min kamp 5

Sammendrag Denne oppgavens hovedanliggende er å sammenligne hovedkarakterene i Agnar Mykles Sangen om den røde rubin og Karl Ove Knausgårds Min Kamp 5 med fokus på selvidentitet som refleksiv prosess. Den amerikanske sosiologen Anthony Giddens sine teorier om identitet i moderniteten utgjør analysens teoretiske fundament. Begge romanene er selvbiografiske verk, og for å sette verkene inn i en sammenheng, har jeg brukt teorier om selvfremstilling, performativ biografisme og dobbeltkontrakt, representert ved Arne Melberg, Jon Helt Haarder og Poul Behrendt. Analysen viser at romankarakterene Ask og Karl Ove skrives fram som to ontologisk usikre unge menn, og at årsaken til usikkerheten er å finne i karakterenes barndom og forholdet til nære omsorgspersoner. Denne usikkerheten gjør at de strever med å besvare det eksistensielle spørsmålet «hvem er jeg?», noe som igjen resulterer i angst, skam, og manglende evne til å holde sin biografiske fortelling i gang. De er så selvbevisste at det å være autentisk blir en umulighet, og dermed ender de med å føle seg utenfor det fellesskapet de begge lengter sånn etter. De forsøker begge å besvare det eksistensielle spørsmålet ved å holde seg i gang i sosiale relasjoner, men for begge er det kunstnerdrømmen som har størst innvirkning på deres selvidentitet. De identifiserer seg begge med mennesker som befinner seg i samfunnets randsone, da det samsvarer med det bruddet de ønsker å skape med etablerte konvensjoner. Analysen viser imidlertid at mens Karl Ove gjør alt han kan for å framstå som kunstner, prøver Ask å skjule denne siden av seg selv for å passe inn. For begge blir avstanden mellom levd liv og den de ønsker å være for stor, og selvidentiteten blir av den grunn svært skjør. Begge romanene har en forteller i historiens nullpunkt, og som vi som lesere vet er sammenfallende med den empiriske forfatteren. Dette setter ulike virkninger i spill, og det skjer i Mykles tilfelle en fordobling av jeget, og hos Knausgård er det snakk om en mangedobling av jeget, i og med at han kommenterer sitt eget prosjekt underveis. Hos Mykle er det et uferdig selv som blir kommentert av det noenlunde ferdige selvet, mens det hos Knausgård foregår en performativ prosess, der selvet skapes underveis i prosessen, også hos forfatteren

The estrogen effect; clinical and histopathological evidence of dichotomous influences in dogs with spontaneous mammary carcinomas.

The purpose of this study was to investigate the associations and explore the relationships between hormonal factors (serum estrogen, estrogen receptors and ovariohysterectomy) and other clinical/histological prognostic factors and their impact on outcome in dogs with mammary carcinomas. Data from two separate prospective studies on dogs with spontaneous mammary carcinomas were used for this research. All dogs underwent standardized diagnostic testing, staging, surgery and follow-up examinations. Serum estrogen was analyzed by competitive enzyme immunoassay or radioimmunoassay, and tumor estrogen receptor (ER) expression was analyzed by immunohistochemistry. A total of 159 dogs were included; 130 were spayed and 29 remained. High serum estrogen was associated with an overall longer time to metastasis (p = 0.021). When stratifying based on spay group, the effect was only significant in spayed dogs, (p = 0.019). Positive tumor ER expression was also associated with a longer time to metastasis (p = 0.025), but similar to above, only in dogs that were spayed (p = 0.049). Further subgroup analysis revealed that high serum estrogen was significantly associated with improved survival in dogs with ER positive tumors, but only in spayed dogs (p = 0.0052). Interestingly, the effect of spaying was the opposite in dogs with ER negative tumors; here, intact dogs with high serum estrogen but ER negative tumors had a significantly longer time to metastasis (p = 0.036). Low serum estrogen was associated with increased risk for the development of non-mammary tumors in the post-operative period (p = 0.012). These results highlight the dual effect of estrogen in cancer: Estrogen acts as a pro-carcinogen in ER positive mammary tumors, but a may have a protective effect in ER negative tumors, potentially via non-receptor mechanisms. The latter is supported by the decreased risk for non-mammary tumors in dogs with high serum estrogen, and explains the increased incidence of certain non-mammary tumors in in dogs spayed at an early age

Kompetansebegrepet. Undervisning, underveis- og sluttvurdering etter fagfornyelsen

Innholdet i dette notatet er basert på eksamensbesvarelser i profesjonsfag, tredje år, avsluttende eksamen i yrkesfaglærerutdanningen for restaurant-og matfag ved OsloMet. Temaet i eksamensoppgaven var «Hvilken betydning har det nye kompetansebegrepet i Fagfornyelsen for undervisning, underveis-og sluttvurdering irestaurant-og matfag fra høsten 2020». Formålet med denne utgivelsen er å dele godt innhold fra eksamensbesvarelsene med skoler som tilbyr utdanningsprogrammet restaurant-og matfag slik at dettekan benyttes somutgangspunkt for skoleutvikling i forbindelse med fagfornyelsen og innføring av ny læreplan i Vg1 fra høsten 2020

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance

Introduction: Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity. Methods: Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; &lt; 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; &lt; 800 kcal/day). Results: A total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant. Conclusions: Neither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance

Supplemental Material, DS1_VET_10.1177_0300985818776054 - Characteristics of the Epithelial-Mesenchymal Transition in Primary and Paired Metastatic Canine Mammary Carcinomas

<p>Supplemental Material, DS1_VET_10.1177_0300985818776054 for Characteristics of the Epithelial-Mesenchymal Transition in Primary and Paired Metastatic Canine Mammary Carcinomas by Talita M. M. Raposo-Ferreira, Becky K. Brisson, Amy C. Durham, Renee Laufer-Amorim, Veronica Kristiansen, Ellen Puré, Susan W. Volk, and Karin Sorenmo in Veterinary Pathology</p

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma

<div><p>Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.</p></div