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OBJECTIVE: To determine the effect of endotoxin (lipopolysaccharide [LPS]) on vasoactive mediator production by cultured equine digital vein endothelial cells (EDVECs). SAMPLE POPULATION: EDVECs obtained from forelimb digital veins of 7 healthy adult horses. PROCEDURES: EDVECs were incubated with or without LPS (1 microg/mL) for 0, 2, 4, 6, 22, and 24 hours. The EDVECs were incubated for 18 hours with LPS (10 pg/mL to 1 microg/mL) with or without ibuprofen, cycloheximide, or L-nitroarginine methyl ester. Medium concentrations of prostacyclin, cyclic guanosine monophosphate, endothelin-1, and thromboxane A(2) were determined. Changes in inducible nitric oxide synthase and cyclooxygenase-2 expression were determined. RESULTS: LPS stimulated mean 4.2- and 14.1-fold increases in EDVEC prostacyclin and cyclic guanosine monophosphate production, respectively, after 22 hours. These effects were LPS concentration-dependent (LPS concentrations that induced a response halfway between the maximum response and baseline of 1.50 and 1.22 ng/mL, respectively). The LPS-induced cyclic guanosine monophosphate production was significantly inhibited (to basal concentrations) by L-nitroarginine methyl ester, and prostacyclin production was inhibited by cycloheximide and ibuprofen. Production of thromboxane A(2) by EDVECs was not detected. Endothelin-1 accumulated in the medium, but LPS did not enhance its production. Inducible nitric oxide synthase expression in EDVECs was not detected with the available antibodies, whereas LPS stimulated cyclooxygenase-2 expression in a time- and concentration-dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: LPS stimulated vasoactive mediator production by equine endothelial cells, which may play a role in LPS-induced digital hypoperfusion.  相似文献   
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The role of endothelium-derived relaxing factors was studied in the regulation of vascular responses in the Krebs perfused equine isolated digit. Perfusion pressure was recorded in response to bolus doses of 5-hydroxytryptamine (6 nmol) alone or co-administered with carbachol (CCh; 0.2 micromol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 micromol). N(omega)-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 microm) caused partial but significant inhibition of CCh-induced vasodilatory response, whereas BK and SP-induced responses were resistant to L-NAME. High potassium (K(+), 30 mm) and the cytochrome P-450 (CYP) epoxygenase inhibitor, clotrimazole (10 microm) plus L-NAME (100 microm), completely abolished the CCh, BK and SP-induced vasodilatory responses, whereas the response to SNP was unaffected. In contrast, the L-NAME-resistant proportion of CCh, BK and SP-induced vasodilatory response was not inhibited by the highly selective CYP2C9 inhibitor, sulphaphenazole (10 microm). The cyclo-oxygenase inhibitor, ibuprofen (10 microm) did not affect the CCh, BK and SP-induced responses. These data demonstrate that CCh, BK and SP-induced relaxation in the equine digit involve a combination of the NO and endothelium-derived hyperpolarizing factor (EDHF) pathways. These results do not support the evidence for the involvement of CYP-derived epoxyeicosatrienoic acids and the exact nature of EDHF in the equine digit remains to be established.  相似文献   
94.
Diagnosis of hyperthyroidism in cats with mild chronic kidney disease   总被引:1,自引:0,他引:1  
OBJECTIVES: In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. METHODS: Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. RESULTS: In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. CLINICAL SIGNIFICANCE: The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.  相似文献   
95.
The DMAC protocol (dexamethasone, melphalan, actinomycin‐D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non‐Hodgkin high‐grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first‐line treatment. Thirty‐five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non‐responders: 62 days (range 28‐952) for CR vs 32 days (range 20‐70) for PR. Six CR received more than six cycles of DMAC (range 7‐36 cycles) and experienced a longer TTD (median 508, range 126‐952 days). Thrombocytopenia occurred in 45% (24 grade 1‐2, 21 grade 3‐4) and neutropenia in 36% of cases (29 grade 1‐2, 7 grade 3‐4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1‐2, 2 grade 3‐4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.  相似文献   
96.
Multi‐agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first‐line chemotherapy to treatment‐naïve canine lymphoma patients with measurable, high grade T‐cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi‐agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild‐to‐moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression‐free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine‐based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first‐line, multi‐agent therapy for patients with HGTCL.  相似文献   
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