Canine mammary tumors (CMT) are very common in female dogs, representing approximately 50% of all tumors in this species, but are highly uncommon in male dogs and are primarily related to hyperestrogenism. There is co...Canine mammary tumors (CMT) are very common in female dogs, representing approximately 50% of all tumors in this species, but are highly uncommon in male dogs and are primarily related to hyperestrogenism. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adipose tissue adjacent to canine mammary tumors. High Precision Liquid Chromatography—HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in one male dog, Akita, 12 years old. After surgery, the mass was carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor was collected to detect environmental contaminants. The pyrethroid was identified as tetramethrin, at 0.20 μg/g. This is the first report in which the environmental contaminant level was detectable in adipose tissue of this male dog with a malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis since this animal did not present any other tumor that could cause hyperestrogenism.展开更多
Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance L...Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.展开更多
Objective To determine whether prostaglandin E2 (PGE2) influences the dog skeletal muscle circulation by a direct action on the vascular smooth muscle or via pre- or post-synaptic modulation of sympathetic neurotransm...Objective To determine whether prostaglandin E2 (PGE2) influences the dog skeletal muscle circulation by a direct action on the vascular smooth muscle or via pre- or post-synaptic modulation of sympathetic neurotransmission.Methods In 18 anaesthetised dogs, a gracilis muscle was vascularly isolated and perfused at constant flow. Sympathetic vasoconstrictor tone on the muscles was reflexly controlled by alterations to the pressure at which the isolated carotid sinuses were perfused. The effects of PGE2 injection into the muscle were compared at low carotid sinus pressure, high carotid sinus pressure, and following denervation of the muscle, with or without noradrenaline infusion.Results At all levels of sympathetic tone, PGE2 produced significantly more vasodilation than the saline vehicle. However, at a carotid sinus pressure of 46.0±2.3 mmHg (1 mmHg=0.133 kPa), PGE2 caused a decrease in femoral arterial perfusion pressure of 52.6±7.1 mmHg, which was significantly greater than the response at a carotid sinus pressure of 208.5±3.7 (33.6±4.2 mmHg decrease) or following denervation (25.6±3.7 mmHg decrease). In a separate group of denervated muscles, PGE2 caused a similar decrease in perfusion pressure in the presence or absence of a noradrenaline infusion.Conclusions PGE2 appears to cause vasodilation through two separate mechanisms: one mechanism involves presynaptic inhibition of sympathetic vasoconstrictor tone, whilst the other is independent of the sympathetic nervous system, and is therefore presumably a direct action on the vascular smooth muscle or endothelium. Under our experimental conditions, both mechanisms contributed equally to the vasodilation.展开更多
文摘Canine mammary tumors (CMT) are very common in female dogs, representing approximately 50% of all tumors in this species, but are highly uncommon in male dogs and are primarily related to hyperestrogenism. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adipose tissue adjacent to canine mammary tumors. High Precision Liquid Chromatography—HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in one male dog, Akita, 12 years old. After surgery, the mass was carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor was collected to detect environmental contaminants. The pyrethroid was identified as tetramethrin, at 0.20 μg/g. This is the first report in which the environmental contaminant level was detectable in adipose tissue of this male dog with a malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis since this animal did not present any other tumor that could cause hyperestrogenism.
基金supported by the Research Foundation of the State of So Paulo (FAPESP/Brazil)National Council of Technological and Scientific Development (CNPq/Brazil)
文摘Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.
文摘Objective To determine whether prostaglandin E2 (PGE2) influences the dog skeletal muscle circulation by a direct action on the vascular smooth muscle or via pre- or post-synaptic modulation of sympathetic neurotransmission.Methods In 18 anaesthetised dogs, a gracilis muscle was vascularly isolated and perfused at constant flow. Sympathetic vasoconstrictor tone on the muscles was reflexly controlled by alterations to the pressure at which the isolated carotid sinuses were perfused. The effects of PGE2 injection into the muscle were compared at low carotid sinus pressure, high carotid sinus pressure, and following denervation of the muscle, with or without noradrenaline infusion.Results At all levels of sympathetic tone, PGE2 produced significantly more vasodilation than the saline vehicle. However, at a carotid sinus pressure of 46.0±2.3 mmHg (1 mmHg=0.133 kPa), PGE2 caused a decrease in femoral arterial perfusion pressure of 52.6±7.1 mmHg, which was significantly greater than the response at a carotid sinus pressure of 208.5±3.7 (33.6±4.2 mmHg decrease) or following denervation (25.6±3.7 mmHg decrease). In a separate group of denervated muscles, PGE2 caused a similar decrease in perfusion pressure in the presence or absence of a noradrenaline infusion.Conclusions PGE2 appears to cause vasodilation through two separate mechanisms: one mechanism involves presynaptic inhibition of sympathetic vasoconstrictor tone, whilst the other is independent of the sympathetic nervous system, and is therefore presumably a direct action on the vascular smooth muscle or endothelium. Under our experimental conditions, both mechanisms contributed equally to the vasodilation.