[Therapy of primary hypoadrenocorticism in dogs with low dose desoxycorticosterone pivalate]. / Therapie des primären Hypoadrenokortizismus beim Hund mit niedrig dosiertem Desoxycorticosteronpivalat.

OBJECTIVE: Since 2016 the only approved drug for the treatment of primary hypoadrenocorticism (Addisons disease) in dogs in Germany is desoxycorticosterone pivalate (DOCP), namely Zycortal®. The initial dose recommended by the manufacturer is 2.2 mg/kg. Our own experience and select publications raise the suspicion that a distinctly lower initial dose would be sufficient. Mainly cost reduction motivates for dose reduction and with it comes a higher owner motivation and compliance. It was the objective of our retrospective study to show that an initial dose of 1.5 mg/kg DOCP is sufficient for controlling canine hypoadrenocorticism. MATERIAL AND METHODS: Dogs with primary hypoadrenocorticism were included if the initial starting dose was 1.5 mg/kg DOCP subcutaneously. The first, second and the last known dose of DOCP were documented. Electrolyte concentrations at the time of diagnosis as well as 10-14 days after the first injection, on the day of the second injection as well as at the last known injection were recorded. A dog was considered medically well-regulated when clinically healthy, sodium and potassium concentrations within the reference ranges, and when the responsible veterinarian did not recommended a dose alteration. RESULTS: All 13 included dogs were clinically healthy after the first or second injection. One dog received 1.6 mg/kg DOCP as last documented dose, all other dogs received ≤ 1.5 mg/kg (median: 1.3, range: 0.4-1.6) DOCP. Eleven dogs were injected once monthly, 2 dogs received injections every 60 days. The dogs were followed at least 7 months (median: 20 months, range: 7-26 months). CONCLUSION AND CLINICAL RELEVANCE: We were able to show that a starting dose of 1.5 mg/kg DOCP (Zycortal®) is sufficient for controlling primary hypoadrenocorticism in dogs. Adjustments of the dose are needed in some dogs. Regular measurement of electrolyte concentrations 10 days after treatment initiation and at the monthly DOCP injection is required for a correct disease management with DOCP.

Characterization of myeloid leukocytes and soluble mediators in pancreatic cancer: importance of myeloid-derived suppressor cells.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumor-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumors build an immunosuppressive cytokine milieu, which correlates with tumor progression. We observed a low frequency of dendritic cells (DC) and a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumors. A strong accumulation of MDSC has also been demonstrated in the peripheral blood of resected PDAC patients. While DC and macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoral VEGF concentration during the PDAC progression. Application of the phosphodiesterase-5 inhibitor sildenafil led to a prolonged survival of PDAC-bearing female mice, which was due to the decrease in MDSC frequencies and in the systemic VEGF level. This led to a restoration of anticancer immune responses, manifested in the recovery of T lymphocyte functions and in an increase in the frequency of conventional CD4+ T cells in tumors and IFNγ level in serum of PDAC-bearing mice. Thus, MDSC are strongly involved in the PDAC-associated immunosuppression and that their depletion could create new approaches for therapy of PDAC.